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Emergency department visits and hospitalizations are common among people receiving cancer treatment, accounting for a large proportion of spending in oncology care and negatively affecting quality of life. As oncology care shifts toward value- and quality-based payment models, there is a need to develop interventions that can prevent these costly and low-value events among people receiving cancer treatment. Risk stratification programs have the potential to address this need and optimally would consist of three components: (1) a risk stratification algorithm that accurately identifies patients with modifiable risk(s), (2) intervention(s) that successfully reduce this risk, and (3) the ability to implement the risk algorithm and intervention(s) in an adaptable and sustainable way. Predictive modeling is a common method of risk stratification, and although a number of predictive models have been developed for use in oncology care, they have rarely been tested alongside corresponding interventions or developed with implementation in clinical practice as an explicit consideration. In this article, we review the available published predictive models for treatment-related toxicity or acute care events among people receiving cancer treatment and highlight challenges faced when attempting to use these models in practice. To move the field of risk-stratified oncology care forward, we argue that it is critical to evaluate predictive models alongside targeted interventions that address modifiable risks and to demonstrate that these two key components can be implemented within clinical practice to avoid unplanned acute care events among people receiving cancer treatment.

Background: Early treatment of hepatocellular carcinoma (HCC) is associated with improved survival, but many patients with HCC do not receive therapy. We aimed to examine factors associated with HCC treatment and survival among incident patients with HCC in a statewide cancer registry. Materials and Methods: All patients with HCC from 2003 through 2013 were identified in the North Carolina cancer registry. These patients were linked to insurance claims from Medicare, Medicaid, and large private insurers in North Carolina. Associations between prespecified covariates and more advanced HCC stage at diagnosis (ie, multifocal cancer), care at a liver transplant center, and provision of HCC treatment were examined using multivariate logistic regression. A Cox proportional hazards model was developed to assess the association between these factors and survival. Results: Of 1,809 patients with HCC, 53% were seen at a transplant center Conclusions: In this population-based cohort of patients with HCC, Medicare/Medicaid insurance, rural residence, and Black race were associated with lower provision of HCC treatment and poorer survival. Efforts should be made to improve access to care for these vulnerable populations.

Purpose Estimates of cancer therapy effects can differ in clinical trials and clinical practice, partly due to underrepresentation of certain patient subgroups in trials. We utilize a hybrid approach, combining clinical trial and real-world data, to estimate the comparative effectiveness of two adjuvant chemotherapy regimens for colon cancer. Methods We identified patients aged 66 and older enrolled in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer. Similar patients were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, initiating adjuvant chemotherapy with either 5-fluorouracil (5FU) alone or in combination with oxaliplatin (FOLFOX). We used logistic regression to estimate the likelihood of trial enrollment as a function of age, sex, and substage. Using inverse odds of sampling weights (IOSW), we compared 5-year mortality in patients randomized to FOLFOX vs 5FU using weighted Cox proportional hazards regression, the Nelson-Aalen estimator for cumulative hazards, and bootstrapping for 95% confidence intervals (CIs). Results There were 690 trial participants and 3834 SEER-Medicare patients. The SEER-Medicare population was older and had a higher proportion of stage IIIB and IIIC patients than the trial. After controlling for differences between populations, the IOSW 5-year HR was 1.21 (0.89, 1.65), slightly farther from the null than the trial estimate (HR = 1.14, 95%CI: 0.87, 1.49). Conclusions This study supports mounting evidence of little to no incremental reduction in 5-year mortality for FOLFOX vs 5FU in older adults with stage II-III colon cancer, emphasizing the importance of combining clinical trial and real-world data to support such conclusions.

Regorafenib is a tyrosine kinase inhibitor approved by the FDA for the treatment of patients with chemotherapy refractory metastatic colorectal cancer (mCRC). Regorafenib inhibits signaling through multiple receptors associated with angiogenesis, metastasis, and tumor immunity. Here, we report biomarker results from LCCC1029, a randomized, placebo-controlled, phase II trial of chemotherapy ± regorafenib in patients with second-line mCRC. A panel of 20 soluble protein biomarkers (termed the Angiome) was assessed in the plasma of 149 patients from the LCCC1029 trial both at baseline and along the treatment continuum. Baseline protein levels were analyzed for prognostic and predictive value for progression-free survival (PFS) and overall survival (OS). Changes in protein levels during treatment were analyzed for potential pharmacodynamic effects. Six markers (HGF, IL6, PlGF, VEGF-R1, OPN, and IL6R) were found to be prognostic for PFS. Nine markers (IL6, TIMP-1, PlGF, VCAM-1, ICAM-1, OPN, TSP-2, HGF, and VEGF-R1) were prognostic for OS. Higher baseline levels of OPN (Pintx = 0.0167), VCAM-1 (Pintx = 0.0216), and PDGF-AA (Pintx = 0.0435) appeared to predict for PFS benefit from regorafenib compared with placebo. VCAM-1 was also potentially predictive of OS benefit from regorafenib compared with placebo (Pintx = 0.0124). On-treatment changes of six markers reflected potential on-target effect of regorafenib. Consistent results were observed in an Italian cohort where 105 patients with late-stage mCRC received regorafenib monotherapy. The key findings of this study suggest that VCAM-1 may be a predictive biomarker for regorafenib benefit, while multiple protein markers may be prognostic of outcome in patients with mCRC.

For over a decade, sorafenib remained the only systemic agent with proven clinical efficacy for patients with advanced hepatocellular carcinoma (HCC). Recent years have seen a proliferation of agents. In the first line, lenvatinib was found to be non-inferior to sorafenib in terms of overall survival (OS), with significantly better progression-free survival and objective response rate. Meanwhile, encouraging efficacy signals were observed in phase I/II studies of immune checkpoint inhibitors as monotherapy in HCC. Although subsequent phase III trials failed to demonstrate statistically significant benefit in OS, other clinically meaningful outcomes were observed, including long-term disease control with a favorable toxicity profile. In addition, a synergistic response has been postulated based on the interplay between antiangiogenic molecular targeted agents and immunotherapy. On this basis, interest has turned toward combination strategies of immunotherapy with these standard-of-care medications in the hope of improving treatment efficacy for advanced HCC, while maintaining tolerable safety profiles. Indeed, preliminary results from phase I studies of lenvatinib plus pembrolizumab and atezolizumab plus bevacizumab have proved favorable, prompting phase III investigations in the frontline setting, and for atezolizumab plus bevacizumab, these positive findings have been substantiated by recent reporting of phase III data from IMbrave150. In this review, we will present the currently available data on combination therapy atezolizumab plus bevacizumab in advanced HCC, and compare these findings to other promising combination treatments, most notably that of lenvatinib plus pembrolizumab.

PURPOSE: Although studies in other clinical areas have shown that patient-clinician communication can positively influence adherence to medications, little is known about how oncologists address medication counseling during routine office visits. We describe patient-oncologist office-based discussions of oral chemotherapy treatment. METHODS: Transcripts of 24 patient-oncologist office visits were obtained from a national database. Patients were aged ≥ 19 years and prescribed capecitabine for colorectal cancer. We developed a structured coding worksheet using medication-counseling concepts previously identified as important to medication adherence and a grounded approach. Two coders reviewed transcripts for oncologists’ provision of medication information, assessment of patients’ adherence to medication, and the provision of self-management support for management of adverse effects. We assessed interrater reliability with Cohen κ statistics. We describe the counseling concepts present within patient-oncologist conversations and present illustrative quotes to describe how they were discussed. RESULTS: Oncologists generally provided patients who had yet to initiate therapy comprehensive medication information; those in the midst of treatment received less information. Oncologists discussed patients’ continued use of the medication (or discontinuation) among all patients who had initiated therapy (N = 18). How the patient was taking the medication (ie, therapy implementation) was less commonly discussed. Medication adverse effects were also discussed in all encounters. Self-management strategies were commonly provided, albeit mostly in response to a presenting symptom and not preemptively. Patients’ use of concurrent medications, financial access to therapy, and assessments of logistical arrangements were discussed more sporadically. CONCLUSION: Using audio recordings from a national sample of patient-oncologist office visits, we identified several potentially important opportunities to enhance medication counseling among patients prescribed capecitabine for the treatment of colorectal cancer.

Background Regorafenib is an oral multikinase inhibitor targeting angiogenesis, oncogenesis, and cancer proliferation/metastasis. This study evaluated the efficacy of regorafenib in refractory biliary tract cancer (BTC) in a multi-institutional phase 2 study. Methods Patients with BTC who progressed on at least 1 line of systemic therapy received regorafenib at 160 mg daily for 21 days on and 7 days off. The primary endpoint was 6-month overall survival (OS), and the secondary endpoints were median OS, progression-free survival (PFS), and objective response rates. Pretreatment plasma was collected for cytokine evaluation. Results A total of 39 patients were enrolled, and 33 were evaluable for efficacy. The median PFS and OS were 3.7 and 5.4 months, respectively, with survival rates of 46.2% at 6 months, 35.9% at 12 months, and 25.6% at 18 months for the intention-to-treat population. For the 33 evaluable patients who received regorafenib for at least 3 weeks, the median PFS and OS were 3.9 and 6.7 months, respectively, with survival rates of 51.5% at 6 months, 39.4% at 12 months, and 27.3% at 18 months. The objective response rate was 9.1%, and the disease control rate was 63.6%. Twenty-eight patients (71.8%) experienced grade 3/4 adverse events. Among the 23 cytokines analyzed, elevated baseline vascular endothelial growth factor D (VEGF-D) was associated with shorter PFS, whereas elevated baseline interleukin 6 (IL-6) and glycoprotein 130 (GP130) were associated with shorter OS. Conclusions Regorafenib demonstrated modest clinical efficacy in heavily pretreated patients with BTC. Further exploration of biomarkers is warranted to identify a group of patients with BTC who may benefit from regorafenib.

Background Preclinical evidence has demonstrated that common intratumor bacteria metabolize the chemotherapeutic drug gemcitabine. The significance of this bacterial metabolism pathway, relative to the known metabolic pathways by host enzymes, is not known. We hypothesized that bacterial metabolism is clinically significant and that “knockdown” by antibacterial therapy has the unintended effect of increasing the effective dose of gemcitabine, thereby increasing the risk for gemcitabine-associated toxicities. Materials and Methods We reanalyzed the comparator arm of the MPACT trial (NCT01442974), made available through Project Data Sphere, LLC (CEO Roundtable on Cancer's Life Sciences Consortium, Cary, NC; www.projectdatasphere.org). In this arm, 430 patients with metastatic pancreatic adenocarcinoma were treated with gemcitabine. We used the Anderson-Gill survival model to compare the risk of developing an adverse event after antibacterial prescription with time unexposed to antibacterials. Adverse events of grade 3 and greater were considered at three levels of granularity: all aggregated into one endpoint, aggregated by class, and taken individually. Antibiotic exposures were analyzed in aggregate as well as by class. Results Antibacterial exposure was associated with an increased risk of adverse events (hazard ratio [HR]: 1.77; confidence interval [CI]: 1.46–2.14), any hematologic adverse event (HR: 1.64; CI: 1.26–2.13), and any gastrointestinal adverse event (HR: 2.14; CI: 1.12–4.10) but not a constitutional (HR: 1.33; CI: 0.611–2.90) or hepatologic adverse event (HR: 0.99; CI: 0.363–2.71). Among specific adverse events, antibacterial exposure was associated with an increased risk of anemia (HR: 3.16; CI: 1.59–6.27), thrombocytopenia (HR: 2.52; CI: 1.31–4.85), leukopenia (HR: 3.91; CI: 1.46–10.5), and neutropenia (HR: 1.53; CI: 1.07–2.17) but not any other specific adverse events. Conclusion Antibacterial exposure was associated with an increased risk of gemcitabine-associated, dose-limiting adverse events, including aggregate hematologic and gastrointestinal events, as well as four specific hematologic adverse events, suggesting that intratumor bacteria may be responsible for a clinically significant portion of gemcitabine metabolism. Alternative avenues of evidence will be necessary to confirm this preliminary finding and assess its generalizability. There is plentiful opportunity for similar analyses on other clinical trial data sets, where gemcitabine or other biomimetic small molecules were used. Implications for Practice Patients treated with gemcitabine for metastatic pancreatic ductal adenocarcinoma have an increased rate of gemcitabine-associated toxicity during and after antibiotic therapy. This observation is consistent with preclinical evidence that intratumor bacteria metabolize gemcitabine to an inactive form. Further research is needed to determine whether this observation merits any changes in clinical practice.

Background: The pharmacy reference database, Micromedex, lists concomitant hydrochlorothiazide and cyclophosphamide use as a potential, major drug–drug interaction (DDI), although only one small, single-center study supports this claim. Our objective was to estimate associations between this potential DDI and two adverse chemotherapy-related events, neutropenia-related hospitalizations and treatment regimen discontinuation, among a cohort of women with breast cancer initiating adjuvant chemotherapy containing cyclophosphamide. Methods: Using linked Surveillance, Epidemiology, and End Results Program (SEER)-Medicare data, we included women 66 years and older with breast cancer diagnosis between 2007 and 2011, who initiated a regimen containing cyclophosphamide. Risk ratios (RR) and 95% confidence intervals for adverse outcomes comparing women exposed versus unexposed to the potential DDI were assessed using modified multivariable Poisson regression adjusting for potential confounders. Results: In total, 27% of women receiving cyclophosphamide treatment were exposed to concomitant hydrochlorothiazide, of which 11% experienced a neutropenia-related hospitalization and 21% discontinued their chemotherapy regimen prior to completion. Adjusted risks of both adverse events were similar between those exposed and unexposed to the potential DDI [neutropenia-related hospitalization: adjusted RR (aRR) = 0.92 (0.70–1.21); treatment discontinuation: aRR = 1.00 (0.96–1.05)]. Conclusions: Our results do not support an association between concomitant hydrochlorothiazide use and two clinically relevant adverse chemotherapy-related events. Impact: Our results support reassessing and potentially lowering severity of this potential interaction in drug reference databases.

CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3 + 3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/m2. The most common grade 3-4 toxicity was lymphopenia, with only 1 grade 4 event. pCR was achieved in 6/32 (19%) patients overall and 2/6 (33%) patients at the weekly MTD. CRLX101 at 15 mg/m2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. Clinicaltrials.gov registration NCT02010567.

PURPOSE CALGB/SWOG 80405 was a randomized phase III trial that found no statistically significant difference in overall survival (OS) in patients with first-line metastatic colorectal cancer treated with chemotherapy plus either bevacizumab or cetuximab. Primary tumor DNA from 843 patients has been used to discover genetic markers of OS. PATIENTS AND METHODS Gene mutations were determined by polymerase chain reaction. Microsatellite status was determined by genotyping of microsatellites. Tumor mutational burden (TMB) was determined by next-generation sequencing. Cox proportional hazard models were used, with adjusting factors. Interaction of molecular alterations with either the bevacizumab or the cetuximab arms was tested. RESULTS Patients with high TMB in their tumors had longer OS than did patients with low TMB (hazard ratio [HR], 0.73 [95% CI, 0.57 to 0.95]; P = .02). In patients with microsatellite instability–high (MSI-H) tumors, longer OS was observed in the bevacizumab arm than in the cetuximab arm (HR, 0.13 [95% CI, 0.06 to 0.30]; interaction P < .001 for interaction between microsatellite status and the two arms). Patients with BRAF mutant tumors had shorter OS than did patients with wild-type (WT) tumors (HR, 2.01 [95% CI, 1.49 to 2.71]; P < .001). Patients with extended RAS mutant tumors had shorter OS than did patients with WT tumors (HR, 1.52 [95% CI, 1.26 to 1.84]; P < .001). Patients with triple-negative tumors (WT for NRAS/ KRAS/ BRAF) had a median OS of 35.9 months (95% CI, 33.0 to 38.8 months) versus 22.2 months (95% CI, 19.6 to 24.4 months ) in patients with at least one mutated gene in their tumors ( P < .001). CONCLUSION In patients with metastatic colorectal cancer treated in first line, low TMB, and BRAF and RAS mutations are negative prognostic factors. Patients with MSI-H tumors benefited more from bevacizumab than from cetuximab, and studies to confirm this effect of MSI-H are warranted.

PURPOSE: The association between geriatric assessment (GA)–identified impairments and long-term health care use in older cancer survivors remains unknown. Our objective was to evaluate whether a GA performed at cancer diagnosis was predictive of hospitalizations and long-term care (LTC) use in older adult cancer survivors. METHODS: Older adults with GA performed between 3 months before through 6 months after diagnosis were included (N = 125). Patients with Medicare Parts A and B coverage and no managed care were identified. Hospitalizations and LTC use (skilled nursing or assisted living) were assessed up to 5 years postdiagnosis. GA risk measures were evaluated in separate Poisson models estimating the relative risk (RR) for hospital and LTC visits, adjusting for age and Charlson comorbidity score. RESULTS: The mean age of patients was 74 years, and the majority were female (80%) and white (90%). Breast cancer (64%) and early-stage disease (stages 0 to III, 77%) were common. Prefrail/frail status (RR, 2.5; P < .001), instrumental activities of daily living impairment (RR, 5.47; P < .001), and limitations in climbing stairs (RR, 2.94; P < .001) were associated with increased hospitalizations. Prefrail/frail status (RR, 1.86; P < .007), instrumental activities of daily living impairment (RR, 4.58; P < .001), presence of falls (RR, 6.73; P < .001), prolonged Timed Up and Go (RR, 5.45; P < .001), and limitations in climbing stairs (RR, 1.89; P < .005) were associated with LTC use. CONCLUSION: GA-identified impairments were associated with increased hospitalizations and LTC use among older adults with cancer. GA-focused interventions should be targeted toward high-risk patients to reduce long-term adverse health care use in this vulnerable population.

Our aim was to evaluate the prognostic impact of three inflammatory markers - neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) - on overall survival (OS) in older adults with cancer.Our sample includes 144 patients age ≥ 65 years with solid tumor cancer who completed a cancer-specific Geriatric Assessment (GA) from 2010 to 2014 and had pretreatment CBC with differential. NLR was dichotomized a previously reported cut-off value of 3.5, while PLR and LMR were dichotomized at the median. Cox proportional hazards models evaluated whether NLR, PLR and LMR were predictive of OS independent of covariates including a recently developed 3-item GA-derived prognostic scale consisting of (1) "limitation in walking several blocks", (2) "limitation in shopping", and (3) "≥ 5% unintentional weight loss in 6 months".Median age was 72 years, 53% had breast cancer, 27% had stage 4 cancer, 14% had Karnofsky Performance Status (KPS) 80, 11% received less intensive than standard treatment for stage, and 39% had NLR 3.5. In univariable analysis, higher NLR and PLR and lower LMR were significantly associated with worse OS. NLR remained a significant predictor of OS (HR = 2.16, 95% CI; 1.10-4.25, p = .025) after adjusting for cancer type, stage, age, KPS, treatment intensity, and the GA-derived prognostic scale.NLR 3.5 is predictive of poorer OS in older adults with cancer, independent of traditional prognostic factors and the GA-derived prognostic scale.

Cancers of unknown primary (CUPs) are histologically confirmed, metastatic malignancies with a primary tumor site that is unidentifiable on the basis of standard evaluation and imaging studies. CUP comprises 2-5% of all diagnosed cancers worldwide and is characterized by early and aggressive metastasis. Current standard evaluation of CUP requires histopathologic evaluation and identification of favorable risk subtypes that can be more definitively treated or have superior outcomes. Current standard treatment of the unfavorable risk subtype requires assessment of prognosis and consideration of empiric chemotherapy. The use of molecular tissue of origin tests to identify the likely primary tumor site has been extensively studied, and here we review the rationale and the evidence for and against the use of such tests in the assessment of CUPs. The expanding use of next generation sequencing in advanced cancers offers the potential to identify a subgroup of patients who have actionable genomic aberrations and may allow for further personalization of therapy.

International audience; Fluoropyrimidines (fluorouracil, capecitabine, and other analogs) are highly used anticancer drugs worldwide. However, patients with cancer treated with these drugs might experience severe, life-threatening toxicity because of germline genetic variation in the DPYD gene. This is a genetic predisposition with an established mechanistic basis that links genetic variation in the DPYD gene to an increase in systemic drug exposure, resulting in an increased risk of toxicity. Pharmacology guidelines provide recommendations on avoiding treatment with fluoropyrimidines or reducing their dose in patients carrying DPYD genetic variants conferring an increased risk of toxicity. However, oncology societies in the United States do not recommend systematic testing. Instead, on April 30, 2020, the European Society for Medical Oncology issued a document recommending genetic testing. In this scenario of contradicting information, practicing oncologists struggle with reaching an informed decision on whether genetic testing should be applied before treatment. This is mostly due to uncertainty about the clinical relevance of genetic testing from the perspective of a practicing oncologist. To reach an informed decision, practicing oncologists need access to concise information on the genetic variants to be tested and a practitioner-friendly interpretation of the test results. We believe this information is currently lacking. To our knowledge, for the first time, we provide a single guide for health care professionals to make an evidence-based decision about DPYD testing for patients with cancer. This article provides the essential knowledge base for oncologists to have an informed discussion with their patients about the genetic testing for DPYD. This document assists practitioners in quickly evaluating whether, when, where, and how to order a DPYD genetic test.

Lymph node metastases from hepatocellular carcinoma (HCC) represents a challenging clinical scenario with a poor prognosis, especially in the setting of prior liver transplant. Long-term survival is achievable in select patients with isolated lymph node metastases who undergo surgical resection, but little data exist regarding non-surgical options. For intrahepatic HCC, stereotactic body radiation therapy (SBRT) has emerged as a standard and effective nonsurgical treatment option. Here, we present three patients (two with prior liver transplant) with isolated lymph node metastases treated with curative intent using SBRT to doses of 30-45 Gy in three to five fractions. Two patients (with follow-up of 27 and 31 months) had a complete or near-complete response and remain cancer-free. One patient had intrahepatic HCC recurrence shortly after SBRT but stable disease in the treated lymph node metastasis at 20 months. Liver function remained excellent after radiation in all three patients, but one patient developed a grade 3 duodenal ulcer at 20 months that resolved with medical management. These cases illustrate the potential utility of SBRT as a non-invasive, definitive treatment option for patients with isolated lymph node metastases from HCC.

RESEARCH OBJECTIVE: Racial disparities in health care experiences and access are well‐documented. Yet, little is known regarding racial variations in the confluence of multiple health care access (HCA) experiences among cancer patients. We identified cancer patient subgroups with similar, co‐occurring HCA experiences, and evaluated racial differences in HCA subgroup membership. STUDY DESIGN: We used data from the University of North Carolina Health Registry/Cancer Survivorship Cohort. Participants completed a baseline questionnaire assessing demographics, health history, health‐related quality of life, and health care experiences. HCA was assessed along five domains (ie, doctor interpersonal manner, doctor communication, financial burden, time spent with doctor, and accessibility/convenience) using the RAND Patient Satisfaction Questionnaire. We used latent profile analysis to identify subgroups of patients with similar HCA experiences. Modified Poisson regressions were estimated to assess racial differences in HCA subgroup membership, adjusting for patient clinical and demographic characteristics. POPULATION STUDIED: Black and white breast, gastrointestinal, genitourinary, and head/neck cancer patients aged 18 or older and enrolled in the University of North Carolina Health Registry/Cancer Survivorship Cohort during 2010 to 2016. PRINCIPAL FINDINGS: Our analysis included 393 black (14.8%) and 2265 white (85.2%) participants. The latent profile analysis resulted in an optimal solution of 5 HCA profiles/subgroups, ranging from Low HCA to High HCA. Members of profile 1 (6.0% of sample) reported “Low” HCA along all HCA domains. Profile 2 (10.8%) consisted of individuals reporting low scores on every HCA domain except “financial burden,” where scores were moderate. Profile 3 (49.9%) members exhibited moderate scores on each HCA domain, while members of profile 4 (11.7%%) reported moderate HCA scores on most HCA domains, with the exception of low scores on “financial burden.” Profile 5 (21.7%) was comprised of patients reporting “High” HCA along every HCA domain. In unadjusted chi‐square comparisons, black patients were more likely to be in the “Low” HCA group (Profile 1) than whites (11.11% vs 5.3%, P

Background Regorafenib, a multikinase inhibitor that inhibits angiogenesis, growth, and proliferation, prolongs survival as monotherapy in patients with refractory colorectal cancer. This international, double-blind, placebo-controlled, multicenter trial assessed the efficacy of regorafenib with folinic acid, fluorouracil, and irinotecan (FOLFIRI) as a second-line treatment for metastatic colorectal cancer. Methods Patients with metastatic colorectal cancer who progressed on first-line oxaliplatin and fluoropyrimidine enrolled at 45 sites in the United States and Ireland. Patients, stratified by prior bevacizumab use, were randomized 2:1 to regorafenib or placebo. The treatment consisted of FOLFIRI on days 1 and 2 and days 15 and 16 with 160 mg of regorafenib or placebo on days 4 to 10 and days 18 to 24 of every 28-day cycle. Crossover was not allowed. The primary endpoint was progression-free survival (PFS). Under the assumption of a 75% event rate, 180 patients were required for 135 events to achieve 90% power to detect a hazard ratio (HR) of 0.65 with a 1-sided α value of .1. Results One hundred eighty-one patients were randomized (120 to regorafenib-FOLFIRI and 61 to placebo-FOLFIRI) with a median age of 62 years. Among these, 117 (65%) received prior bevacizumab or aflibercept. PFS was longer with regorafenib-FOLFIRI than placebo-FOLFIRI (median, 6.1 vs 5.3 months; HR, 0.73; 95% confidence interval [CI], 0.53-1.01; log-rank P = .056). The median overall survival was not longer (HR, 1.01; 95% CI, 0.71-1.44). The response rate was higher with regorafenib-FOLFIRI (34%; 95% CI, 25%-44%) than placebo-FOLFIRI (21%; 95% CI, 11%-33%; P = .07). Grade 3/4 adverse events with a >5% absolute increase from regorafenib included diarrhea, neutropenia, febrile neutropenia, hypophosphatemia, and hypertension. Conclusions The addition of regorafenib to FOLFIRI as second-line therapy for metastatic colorectal cancer only modestly prolonged PFS over FOLFIRI alone. Cancer 2018. © 2018 American Cancer Society.

Objective Computerized tomography (CT) imaging is routine in oncologic care and can be used to measure muscle quantity and composition that may improve prognostic assessment of older patients. This study examines the association of single-slice CT-assessed muscle measurements with a frailty index in older adults with cancer. Materials and Methods Using the Carolina Senior Registry, we identified patients with CT imaging within 60days ± of geriatric assessment (GA). A 36-item Carolina Frailty Index was calculated. Cross-sectional skeletal muscle area (SMA) and Skeletal Muscle Density (SMD) were analyzed from CT scan L3 lumbar segments. SMA and patient height (m 2 ) were used to calculate skeletal muscle index (SMI). Skeletal Muscle Gauge (SMG) was calculated by multiplying SMI×SMD. Results Of the 162 patients, mean age 73, 53% were robust, 27% pre-frail, and 21% frail. Significant differences were found between robust and frail patients for SMD (29.4 vs 24.1 HU, p p =0.003), but not SMI (41.9 vs 39.5cm 2 /m 2 , p =0.29). After controlling for age and gender, for every 5 unit decrease in SMD, the prevalence ratio of frailty increased by 20% (PR=1.20 [1.09, 1.32]) while the prevalence of frailty did not differ based on SMI. Conclusions Muscle mass (measured as SMI) was poorly associated with a GA-based frailty index. Muscle density, which reflects muscle lipid content, was more associated with frailty. Although frailty and loss of muscle mass are both age-related conditions that are predictive of adverse outcomes, our results suggest they are separate entities.

42 Background: As value-based payment models for cancer care expand, the need for measures which reliably assess the quality of care provided increases. This is especially true for models like the Oncology Care Model (OCM) that rely on quality rankings to determine potential shared savings. Under models like these, unreliable measures may result in arbitrary application of value-based payments. The goal of this project is to evaluate the extent to which measures used within the OCM are reliable indicators of provider performance. Methods: Data for this project came from North Carolina Medicare claims from 2015-2017. Episodes were attributed to physician practices at the tax identification number (TIN) level, lasted 6 months, and were divided into two performance years beginning 1/1/2016 and 7/1/2016. TINs with fewer than 20 attributed patients were excluded. Three claims-based OCM measures were used in this evaluation: 1) proportion of episodes with all-cause hospital admissions; 2) proportion of episodes with all-cause emergency department (ED) visits or observation stays; and 3) proportion of patients that died who were admitted to hospice for 3 days or more. Risk adjustment followed the method described by measure specifications from the OCM. Reliability was calculated as the ratio of between practice variation (e.g. signal) to the sum of between practice variation and within practice variation (e.g. noise). Variance estimates were derived from hierarchical logistic regression models used for risk adjustment. Results: For the hospitalization and ED visit measures, episode counts for years 1 and 2 were 30,746 and 28,430 and TIN counts were 86 and 84, respectively. Hospice use measures had fewer episodes (2,677 and 2,428) and TINs (36 and 33). Across all measures, median reliability scores failed to achieve the recommended 0.7 threshold and only hospice had a median reliability score above 0.5 (Table). Conclusions: These findings suggest claims-based measures included in the OCM may produce imprecise estimates of provider performance and are vulnerable to random variation. Consideration should be given to developing alternative measures which may be more reliable estimates of provider performance and to increasing minimum denominator requirements for existing measures.[Table: see text]

139 Background: Adjustment for social determinants of health (SDOH) when assessing provider care quality remains limited. The Oncology Care Model (OCM), for example, includes low-income status/dual eligibility (LIS/DE) as a part of the risk adjustment model for some quality measures, but does not account for any social risk variables in the hospice measure. No measures within the OCM account for additional social risk factors beyond LIS/DE such as patients’ race, rurality, and social deprivation. Additional SDOH adjustment could increase the accuracy of provider quality rankings and better align performance-based payments with true provider quality. Methods: North Carolina Medicare claims from 2015-2017 comprised the data for this study. The year 2015 was used to establish baseline covariates. Episodes were attributed to physician practices’ Tax Identification Number (TIN), lasted 6 months, and were divided into performance years beginning 1/1/2016 and 7/1/2016. Three measures were used: 1) all-cause hospital admissions; 2) all-cause emergency department visits or observation stays; and 3) admission to hospice for 3 days or more among patients who died. SDOH included patient-level race as well as county-level rurality and social deprivation, measured using the social deprivation index (SDI). TIN-level scores with and without expanded SDOH variables were divided into quintiles and compared descriptively as well as using weighted kappa statistics. Results: No SDOH were significantly associated with the hospitalization outcome (P = 0.118-0.944). For the ED measure, Black patients and rural patients were significantly more likely to have an ED visit or observation stay during an episode than white patients and urban patients (P < 0.0001). For the hospice measure, greater SDI values were associated with less hospice use (P < 0.05). Accordingly, including SDOH variables for ED visit/observation stay and hospice measures had a greater impact on TIN rankings than for the hospitalization measure (Table). Conclusions: Because quintile rankings in determine potential shared savings under models like the OCM, differences in rankings due to additional SDOH variables could have a meaningful impact on TIN-level revenue. Additional work is needed to expand the scope of patient-level SDOH variables used for risk adjustment and to explore differences across TINs which contribute to SDOH-sensitive changes in rankings.[Table: see text]

The only US Food and Drug Administration (FDA)-approved first-line systemic therapy for hepatocellular carcinoma (HCC) is sorafenib; however, resistance or intolerance to sorafenib is unfortunately common. In this review, we briefly describe systemic therapies that can be considered for patients with HCC who show resistance or intolerance to sorafenib. For all patients with HCC who need systemic therapy, we strongly advocate for participation in clinical trials. Cytotoxic chemotherapy plays a minor role in the treatment of advanced HCC, with some data supporting the use of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) and GEMOX (gemcitabine-oxaliplatin). Multi-target kinase inhibitors such as lenvantinib and regorafenib have recently met their primary endpoints as first- and second-line therapy, respectively, with regorafenib now representing the only FDA-approved drug for second-line treatment of HCC. Other targeted therapies remain under investigation, but results so far have not significantly changed clinical practice. Immunotherapy is an interesting area of research in the treatment of HCC with preclinical and early clinical data demonstrating exciting results; thus numerous investigational studies are currently focusing on immunotherapy in the treatment of HCC. While systemic treatment options in HCC remain a challenge for providers, in this review, we summarize the current literature and highlight areas of progress with respect to the treatment of patients with HCC and resistance or intolerance to sorafenib.

Outcomes for metastatic colorectal cancer have improved progressively with the incorporation of new drugs into standard treatment regimens. Most recently, targeted therapies against VEGF and EGFR have improved upon the prior standard for first-line therapy with FOLFOX or FOLFIRI. As attempts to combine anti-VEGF and anti-EGFR drugs have been unsuccessful, it is necessary to choose between them when beginning first-line therapy. This review summarizes the existing literature to best inform this decision. To date, three head-to-head trials have compared anti-EGFR and anti-VEGF therapy in RAS wild-type patients: PEAK, FIRE-3, and CALGB/SWOG 80405. PEAK and FIRE-3 suggested a survival advantage for anti-EGFR therapy over anti-VEGF therapy, though CALGB/SWOG 80405 did not. Results have emerged recently to suggest that tumors arising from the right colon are resistant to anti-EGFR therapy, and that any advantage of anti-EGFR therapy over anti-VEGF therapy may be limited to left-sided tumors.

Introduction: Hepatocellular carcinoma (HCC) is a poor-prognosis cancer with a high symptom burden. Multidisciplinary HCC care is complex and unique in cancer medicine. We sought to determine whether the distinct process affects hospice use and how hospice affects end-of-life acute care utilization. Patients and Methods: Patients dying after HCC diagnosed from 2004 to 2011 were identified within SEER-Medicare. Hospice use and associated factors were described using logistic regression. Coarse exact and propensity score matching created groups of hospice and nonhospice comparators balanced on clinical characteristics. Health care use from first hospice claim to death and the matched duration in the nonhospice group were compared. Results: Of 7,992 decedent patients with HCC, 63% used hospice before death, with a median duration of 18 days (interquartile range, 5-51 days). Initial treatment with surgery and ablation (odds ratio [OR], 0.63; 95% CI, 0.53 to 0.74) or chemoembolization/radioembolization (OR, 0.71; 95% CI, 0.62 to 0.80) was associated with decreased odds of subsequent hospice use compared with untreated patients. Hospice use was more likely in those consulting hematology/oncology (OR, 1.33; 95% CI, 1.13 to 1.56) but not in those consulting gastroenterology (OR, 0.79; 95% CI, 0.65 to 0.95). Hospice patients had lower rates of hospitalization (7.9% v 47.8%; risk ratio [RR], 0.16; 95% CI, 0.14 to 0.19), intensive care unit stay (2.8% v 25.3%; RR, 0.11; 95% CI, 0.09 to 0.14), and in-hospital death (3.5% v 58.4%; RR, 0.06; 95% CI, 0.05 to 0.07). Conclusion: Processes of care influence which patients with HCC are referred to hospice. Hospice use has a marked effect on acute care use at the end of life in patients with HCC. Efforts to incorporate cancer-focused palliative care might improve the quality of end-of-life care in HCC.

Background Pharmacist-led medication reconciliation (PMR) ensures adequate recording and use of medications by patients. PMR may be important for cancer patients initiating new therapies, as they have a high burden of medication use and are more susceptible to inadvertent medication discrepancies. To describe medication changes (additions, discontinuations, and modifications) made to the electronic health record during a PMR among cancer patients initiating chemotherapy. Methods From October 2011 to March 2012, 397 cancer patients initiating chemotherapy underwent a PMR at the University of North Carolina Cancer Hospital. Self-reported medications and those in the patients’ electronic health record were reviewed. Log-binomial regression models were used to estimate adjusted prevalence ratios and 95% confidence intervals for the associations between patient characteristics and medication changes made to the electronic health record. Results Mean age at time of the PMR was 58. Median number of medications taken prior to the PMR was 10 and median time to PMR completion was 11 min. Vitamins and herbal supplements accounted for the largest proportion of medication additions (38%) and modifications (20%). Antimicrobials accounted for the largest share of discontinuations (15%). After adjustment for all other covariates, patients aged 60–69 years were more likely to have additions than those aged 50 and under (aPR = 1.47, 95%CI: 1.10–1.97). Patients 70 years and over were more likely to have modifications (aPR = 1.74, 95%CI: 1.07–2.82). Conclusion Our results show that most cancer patients had a medication change in the electronic health record. A brief oncology PMR can accurately capture and improve medication safety by preventing prescribing and administration errors.

Background Academic physicians, such as those affiliated with National Cancer Institute (NCI)–designated Comprehensive Cancer Centers, may have different practice patterns regarding the use of high-cost cancer drugs than nonacademic physicians. Materials and Methods For this cohort study, we linked cancer registry, administrative, and demographic data for patients with newly diagnosed cancer in North Carolina from 2004 to 2011. We selected cancer types with multiple U.S. Food and Drug Administration–approved, National Comprehensive Cancer Network–recommended treatment options and large differences in reimbursement between higher-priced and lower-priced options (stage IV colorectal, stage IV lung, and stage II–IV head-and-neck cancers). We assessed whether provider's practice setting—NCI-designated Comprehensive Cancer Center (“NCI”) versus other location (“non-NCI”)—was associated with use of higher-cost treatment options. We used inverse probability of exposure weighting to control for patient characteristics. Results Of 800 eligible patients, 79.6% were treated in non-NCI settings. Patients treated in non-NCI settings were more likely to receive high-cost treatment than patients treated in NCI settings (36.0% vs. 23.2%), with an unadjusted prevalence difference of 12.7% (95% confidence interval [CI], 5.1%–20.0%). After controlling for potential confounding factors, non-NCI patients remained more likely to receive high-cost treatment, although the strength of association was attenuated (adjusted prevalence difference, 9.6%; 95% CI −0.1%–18.7%). Exploratory analyses suggested potential heterogeneity across cancer type and insurance status. Conclusion Use of higher-cost cancer treatments may be more common in non-NCI than NCI settings. This may reflect differential implementation of clinical evidence, local practice variation, or possibly a response to the reimbursement incentives presented by chemotherapy billing.

Background Multiple claims-based proxy measures of poor function have been developed to address confounding in observational studies of drug effects in older adults. We evaluated agreement between these measures and their associations with treatment receipt and mortality in a cohort of older colon cancer patients. Methods Medicare beneficiaries age 66+ diagnosed with stage II-III colon cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare database (2004-2011). Poor function was operationalized by: (1) summing the total poor function indicators for each model; and (2) estimating predicted probabilities of poor function at diagnosis. Agreement was evaluated using Fleiss' κ and Spearman's correlation. Associations between proxy measures and: (1) laparoscopic versus open surgery; (2) chemotherapy versus none; (3) 5-fluorouracil (5FU)+oxaliplatin (FOLFOX) versus 5FU monotherapy; and (4) 1-year mortality were estimated using log-binomial regression, controlling for age, sex, stage, and comorbidity. Survival estimates were stratified by functional group, age, and comorbidity. Results Among 29,687 eligible colon cancer patients, 67% were 75+ years and 45% had stage III disease. Concordance across the poor function indicator counts was moderate (κ: 0.64) and correlation of predicted probability measures varied (ρ: 0.21-0.74). Worse function was associated with lower chemotherapy and FOLFOX receipt, and higher 1-year mortality. Within age and comorbidity strata, poor function remained associated with mortality. Conclusions While agreement varied across the claims-based proxy measures, each demonstrated anticipated associations with treatment receipt and mortality independent of comorbidity. Claims-based comparative effectiveness studies in older populations should consider applying one of these models to improve confounding control.

Upfront chemoradiation with omission of surgery (CR-only) is increasingly being used to treat rectal cancer. When CR-only is used with curative intent, intense surveillance is recommended. We hypothesized that in practice, few patients treated with CR-only receive intensive post-treatment surveillance.Using Surveillance, Epidemiology, and End Results (SEER)-Medicare, all nonmetastatic rectal cancer patients (≥66 years old) diagnosed from 2004 to 2012, who received upfront chemoradiation, were included. Patients who received CR-only were compared with patients receiving neoadjuvant therapy plus proctectomy. In the 24 months after treatment, markers of surveillance, including carcinoembryonic antigen testing (CEA), endoscopy, and imaging, were compared between groups.A total of 2,482 individuals met the inclusion criteria: 21% (n = 514) had CR-only and 79% had conventional treatment (ie chemoradiation plus proctectomy). Only 2.5% and 3.4% of those in the CR-only and conventional treatment groups, respectively, were in complete compliance with National Comprehensive Cancer Network surveillance guidelines during the first 2 years post-treatment (p0.01). The CR-only group was less likely than the conventional treatment group to receive: CEA (adjusted risk ratio [aRR] 0.57; 95% CI 0.50 to 0.65), endoscopy (aRR 0.76; 95% CI 0.66 to 0.87), and office visits (aRR 0.88; 95% CI 0.84 to 0.92), respectively. However, there were similar rates of cross-sectional imaging between groups (aRR 1.31; 95% CI 0.93 to 1.85).Adherence to guideline-recommended surveillance was poor for all Medicare patients with rectal cancer. Despite recommendations for closer follow-up, patients treated with CR-only were less likely to receive surveillance than those treated with conventional treatment. Efforts should be made to increase adherence to surveillance guidelines for all rectal cancer patients treated with curative intent, but particularly for those with higher risk of recurrence, such as those treated with CR-only.

e18706 Background: Real-world patients often differ from trial participants in prognostic factors such as age, sex, and cancer substage. New methods combine covariate data from real-world patients (the “target population”) with outcome and covariate data from a trial to estimate treatment effects in the target population that take these differences into account. With some assumptions, these methods can also estimate outcomes under treatment regimens not studied in the trial such as “what if we only gave six cycles of chemotherapy?” or “what if patients all perfectly followed a protocol?” Methods: Data from the MOSAIC trial of 5-fluorouracil (5FU) vs oxaliplatin + 5FU (FOLFOX) were combined with covariate data from a target population of stage III colon cancer patients in the US Oncology Network meeting trial eligibility criteria. We used weighting and G-computation to estimate five-year mortality and treatment-related paresthesia risk in the target population for four regimens: treatment with up to 12 cycles of 5FU, if providers used their discretion on dose reductions and delays (5FU-MD); up to 12 cycles of FOLFOX with similar physician discretion (FOLFOX-MD); up to 6 cycles of FOLFOX, with providers perfectly following a strict and specific protocol of dose reductions and delays (6-cycle FOLFOX-P, “P” for “per protocol”); and up to 12 cycles of FOLFOX, following the same strict protocol (12-cycle FOLFOX-P). Results: Tablepresents five-year all-cause mortality and paresthesia risk under each regimen in the stage III target population estimated from the models built in trial participants. Paresthesia risk increased with cumulative oxaliplatin dose. Estimated 5-year mortality was lowest with 12-cycle FOLFOX-P. Conclusions: In a target population of US Oncology Network patients with stage III colon cancer, strict protocols of 12 cycles of FOLFOX were predicted to improve survival compared to strict 6-cycle FOLFOX regimens or less strict 12-cycle FOLFOX and 5FU regimens at the cost of substantial increases in side effects. While estimates of risk differences in 5-year mortality were imprecise, combining trial and real-world data and then using weights and G-computation allowed estimation of benefits and harms of multiple regimens in a clinically relevant patient population.[Table: see text]

TPS3618 Background: The superiority of inhibition of programmed cell death-1 (PD-1) pathway in dMMR/MSI-H over chemotherapy with either anti-vascular endothelial growth factor receptor (VEGFr) or anti- epithelial growth factor receptor (EGFr) antibodies in mCRC has been demonstrated in a phase III trial (N Engl J Med 2020; 383:2207). However, more patients had progressive disease as the best response in the anti-PD1 monotherapy arm (29.4% vs. 12.3%) with mean progression-free survival (PFS) of 13.7 months. Preclinical models have demonstrated synergistic interactions between FOLFOX, anti-VEGF, and anti-PD-1. We hypothesize that the dMMR/MSI-H mCRC patients may be more effectively treated by the combination of PD-1 pathway blockade and mFOLFOX6/bevacizumab (bev) rather than with anti-PD-L1 therapy (atezo) alone. Methods: Initially a three-arm study, the mFOLFOX6/bev arm was closed to new enrollment on 6-4-20 due to emerging data; the redesigned COMMIT trial was reactivated on 1/29/2021 as a prospective phase III open-label trial that randomizes (1:1) mCRC dMMR/MSI-H pts (N=211) to either atezo monotherapy or mFOLFOX6/bev+atezo combination. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Primary endpoint is PFS as assessed by site investigator. Secondary endpoints include overall survival (OS), objective response rate (RECIST v1.1), safety profile, disease control rate, duration of response, and centrally-reviewed PFS. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2) or MSI-H by local CLIA-certified PCR or NGS panel; and measurable disease per RECIST. Clinical trial: NCT02997228. Support: U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.

1521 Background: Patterns of chemotherapy delivery are likely to differ between trial and real-world populations. Typical measures used to compare these patterns are calculated at treatment completion, potentially missing key differences in the timing and trajectory of delays and dose reductions. We used a new measure, longitudinal cumulative dose (LCD), to compare treatment delivery over time in trial and real-world populations. Methods: We compared chemotherapy delivery in patients with stage II-III colon cancer enrolled in the MOSAIC trial of 5-fluorouracil (5FU) vs oxaliplatin + 5FU (FOLFOX4) to patients treated from 2008-2019 in the US Oncology Network with FOLFOX4, FOLFOX6, or mFOLFOX6. For each patient, we computed oxaliplatin LCD as the cumulative oxaliplatin dose received at a given timepoint (t) divided by the final standard oxaliplatin dose. We then estimated the median and 25th and 75th percentiles for oxaliplatin LCD within each regimen at day 68 (before the standard timing of the 7th dose), 168 (two weeks after the standard end of treatment), and 250. Results: The table shows the number of patients receiving each treatment regimen and the median and interquartile range for oxaliplatin LCD at each time. Higher LCDs in the trial show delivery closer to standard treatment, meaning fewer delays, dose reductions, and discontinuations. Differences between the medians, 25th percentiles, and 75th percentiles of LCD in each regimen were small at day 68 but grew considerably by days 168 and 250. Conclusions: Divergence from the standard dosing schedule was larger in real-world versus trial settings and varied by oxaliplatin regimen. LCD, as a longitudinal measure, showed that differences in delivery between trial and real-world populations grew substantially over time (even after 168 days and the standard end of treatment) possibly as real-world patients experienced more side effects and barriers to treatment than trial participants. These discrepancies in LCD may cause poorer outcomes in real-world settings than expected based on randomized trials.[Table: see text]

7 Background: Panitumumab is a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR) and is a standard therapy in KRAS/NRAS/BRAF WT mCRC. Preclinical data shows that anti-EGFR therapy causes a tumor-specific adaptive immune response and immunogenic apoptosis, with functional adaptive immunity required to mediate efficacy. However, resistance to anti-EGFR antibody therapy inevitably develops and is associated with increased expression of CTLA-4 and PD-L1. We hypothesized that addition of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) to panitumumab will increase response rate in patients with KRAS/NRAS/BRAF WT MSS mCRC. Methods: LCCC1632 was a multicenter, single-arm, Simon’s two stage phase II clinical trial with a pre-specified safety run-in of panitumumab, ipilimumab, and nivolumab in KRAS/NRAS/BRAF WT, MSS mCRC (NCT03442569). Eligible patients must have received 1-2 prior lines of therapy and no prior anti-EGFR or immune checkpoint inhibitor therapy. Subjects received ipilimumab 1 mg/kg IV q6wk, nivolumab 240 mg IV q2wk, and panitumumab 6 mg/kg IV q2wk until progression, toxicity, or patient withdrawal. The primary endpoint was response rate at 12 weeks per RECIST 1.1, and key secondary endpoints included progression-free survival and duration of response. Results: A total of 56 subjects were enrolled 3/2018-6/2020. This included the 6-subject safety run-in, with 0/6 dose-limiting toxicities in first 12 weeks. The first stage of the Simon’s two-stage clinical trial (n=32) had sufficient response rate to merit full enrollment. There were 7 unevaluable subjects for the primary endpoint of 12-week response rate. Among 49 evaluable subjects, 12-week response rate was 35% (95% CI 21-48; n=17 responses). Twenty subjects had at least an unconfirmed response at any time. Median PFS was 5.7 months (95% CI 5.5-7.9). There was one treatment-related grade 5 adverse event of myocarditis. The most common treatment-related grade 3-4 AEs included lipase increased (9%), amylase increased (7%), ALT increased (5%), AST increased (5%), diarrhea (5%), hypophosphatemia (5%), and maculopapular rash (5%). Conclusions: The combination of panitumumab, ipilimumab, and nivolumab demonstrated evidence of activity and met its prespecified primary endpoint of 12-wk response rate criteria to merit further study. The PFS in this single-arm study compares favorably to expected PFS for anti-EGFR monotherapy in RAS wild-type patients, and results suggest activity of immune checkpoint inhibitors combined with anti-EGFR therapy in MSS mCRC. Clinical trial information: NCT03442569.

TPS232 Background: Despite the superiority in progression-free survival (PFS) of inhibition of programmed cell death-1 (PD-1) pathway in dMMR/MSI-H as compared to chemotherapy with either anti-vascular endothelial growth factor receptor (VEGFr) or anti-epithelial growth factor receptor (EGFr) antibodies in mCRC, more pts had progressive disease as the best response in the anti-PD1 monotherapy arm (29.4% vs. 12.3%) with mean PFS of 13.7 months ( N Engl J Med 2020; 383:2207). We hypothesize that the dMMR/MSI-H mCRC pts may be more effectively treated by the combination of PD-1 pathway blockade and mFOLFOX6/bevacizumab (bev) rather than with anti-PD-1 therapy (atezo) alone. Preclinical work demonstrated synergistic effects between anti-PD-1/anti-VEGF and between oxaliplatin/anti-PD-1 in murine CRC models and phase II data showed activity of anti-PD-1/anti-VEGF in chemotherapy refractory colon cancer. Additionally, in other solid tumor malignancies, anti-PD1 plus anti-VEGFr (i.e., HCC and RCC) as well as anti-PD1 plus chemotherapy (i.e., gastric and esophageal cancers) combinations are standard first-line treatments. Methods: The redesigned COMMIT study was reactivated on 1/29/2021 as a two-arm prospective phase III open-label trial randomizing (1:1) mCRC dMMR/MSI-H (211 pts) to atezo monotherapy versus mFOLFOX6/bev+atezo combination. Assuming our control arm, atezo monotherapy, 48% PFS at 24 months, as assessed by site investigator, we have 80% power to detect a hazard ratio of 0.6 (equivalent to 64.4% PFS at 24 months) with alpha 0.025 one-sided. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Secondary endpoints include OS, objective response rate, safety profile, disease control rate, duration of response, and centrally-reviewed PFS. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2) or MSI-H by local CLIA-certified PCR or NGS panel; and measurable disease per RECIST. Enrollment actively continues to the target accrual of 211 patients randomized between the two immunotherapy arms. Support: U10CA180868, -180822, -180888, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.

Context Many advanced patients with cancer have unrealistic prognostic expectations. Objectives We tested whether offering life expectancy (LE) statistics within palliative chemotherapy (PC) education promotes realistic expectations. Methods In this multicenter trial, patients with advanced colorectal and pancreatic cancers initiating first or second line PC were randomized to usual care versus a PC educational tool with optional LE information. Surveys at two weeks and three months assessed patients' review of the LE module and their reactions; at three months, patients estimated their LE and reported occurrence of prognosis and end-of-life (EOL) discussions. Wilcoxon tests and proportional odds models evaluated between-arm differences in LE self-estimates, and how realistic those estimates were (based on cancer type and line of treatment). Results From 2015 to 2017, 92 patients were randomized to the intervention and 94 to usual care. At baseline most patients (80.9%) wanted “a lot” or “as much information as possible” about the impact of chemotherapy on LE. Among patients randomized to the intervention, 52.0% reviewed the LE module by two weeks and 66.7% by three months—of whom 88.2% reported the information was important, 31.4% reported it was upsetting, and 3.9% regretted reviewing it. Overall, patients' LE self-estimates were very optimistic; 71.4% of patients with colorectal cancer estimated greater than five years; 50% pancreatic patients estimated greater than two years. The intervention had no effect on the length or realism of patients' LE self-estimates, or on the occurrence of prognostic or EOL discussions. Conclusions Offering LE information within a PC educational intervention had no effect on patients' prognostic expectations.

Patient-centered communication (PCC) is an essential component of patient-centered care and contributes to patient satisfaction, health-related quality of life, and other important patient outcomes. The aim of this study was to develop and test survey questions to assess patients’ experiences with PCC in cancer care. We used a conceptual model developed by the National Cancer Institute as our framework. The survey questions align with the six core functions of PCC defined in the model: Exchanging Information, Managing Uncertainty, Enabling Patient Self-Management, Fostering Healing Relationships, Making Decisions, and Responding to Emotions. The study focused on colorectal cancer patients. We conducted two rounds of cognitive interviewing to evaluate patients’ ability to understand and provide valid answers to the PCC questions. Interviews were conducted in Maryland and North Carolina in 2014. We involved a patient advocacy group, Fight Colorectal Cancer, and a multidisciplinary panel of stakeholders throughout the measurement development process to ensure that the survey questions capture aspects of PCC that are important to patients and meet the needs of potential end users, including researchers, healthcare organizations, and health professionals. Patient and other stakeholder input informed revisions of draft survey questions, including changes to survey instructions, frame of reference for questions, response scales, and language. This study demonstrated the feasibility and value of engaging patients and other stakeholders in a measurement development study. The Patient-Centered Outcomes Research Institute (PCORI) conceptual model of patient-centered outcomes research provides a useful guide for patient engagement in research. Research funders should call for meaningful roles for patients and other stakeholders in health research, including in the development of patient-centered outcomes.

Background: Black patients with cancer report worse symptom burden and management relative to Whites. Use of electronic patient-reported outcomes (ePROs) have been linked to improved cancer-related symptom management, with potential to address inequities in symptom management. Visualization of ePRO symptom data is a critical component of ePRO development; however, engagement of diverse patient and family stakeholders in the visualization of ePRO data has been limited. As part of the Symptom and Healthcare Access Reporting and Evaluation (SHARE) study, we engaged diverse stakeholders in the development of an ePRO tool. Herein, we describe our stakeholder engagement process, as well as feedback and recommendations for optimizing visualization of ePRO data with an equity prioritization lens. Methods: We leveraged a multi-step, mixed-methods, community-engaged research approach to solicit input from diverse patients in active treatment (n= 30 Black; n=49 White) and members of cancer-focused community advisory boards (n=1 Asian; n=8 White). Stakeholders provided feedback on two versions of the ePRO symptom report (Prototype 1[original version] and Prototype 2 [modified version based on initial stakeholder feedback]) through an iterative process. Feedback was obtained via surveys, individual interviews, and group meetings. Results: Compared with White patients, Blacks reported more challenges in using and understanding Prototype 1 of the symptom report. Community advisory board members shared similar concerns regarding ease of use of Prototype 1. In particular, patients and members noted that graphical legends and axes were difficult to interpret, making it difficult to identify which symptoms were worsening or improving. Prototype 2 of the ePRO symptom report incorporated feedback, such as increasing font and graph sizes, combining related symptoms (e.g., nausea and vomiting) into a single graph, and inclusion of color-graded graph schemes corresponding to symptom severity (e.g., green=no symptom; orange=moderate severity), which facilitated ease of use for patients with limited graphical literacy. In comparing Prototype 1 to Prototype 2, community advisory board members reported that Prototype 2 was more visually appealing and easier to use and understand. Conclusions: Overall, feedback from diverse patients and community stakeholder groups resulted in the development of a more usable and patient-centered ePRO symptom summary report. Our work highlights the importance and value of engaging diverse stakeholders in the development of ePRO systems, including the visualization of ePRO data, in order to optimize the in the use of ePRO tools for everyone. Citation Format: Wendi L. Elkins, Neda R. Padilla, Dani Cutts, Mattias Jonsson, Michelle Johnson, Giselle Corbie-Smith, Samuel Cykert, Bryce B. Reeve, Antonia V. Bennett, Donald L. Rosenstein, Hanna Sanoff, Cleo A. Samuel. Engaging diverse patients and families in the visualization of cancer-related patient-reported outcomes [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-042.

INTRODUCTION: Liver cancer–secreted serine protease inhibitor Kazal (LC-SPIK) is a protein that is specifically elevated in cases of hepatocellular carcinoma (HCC). We assessed the performance of LC-SPIK in detecting HCC, including its early stages, in patients with cirrhosis, hepatitis B virus (HBV), and hepatitis C virus (HCV). METHODS: We enrolled 488 patients, including 164 HCC patients (81 early HCC) and 324 controls in a blinded, prospective, case–control study. Serum LC-SPIK levels were determined by an enzyme-linked immunosorbent assay-based assay. The performance of serum LC-SPIK and α-fetoprotein (AFP), including area under the curve (AUC), sensitivity, and specificity, are compared. The performance of LC-SPIK was evaluated in an independent validation cohort with 102 patients. RESULTS: In distinguishing all HCC patients from those with cirrhosis and chronic HBV/HCV, LC-SPIK had an AUC of 0.87, with 80% sensitivity and 90% specificity using a cutoff of 21.5 ng/mL. This is significantly higher than AFP, which had an AUC of 0.70 and 52% sensitivity and 86% specificity using a standard cutoff value of 20.0 ng/mL. For early-stage HCC (Barcelona Clinic Liver Cancer stage 0 and A), LC-SPIK had an AUC of 0.85, with 72% sensitivity and 90% specificity, compared with AFP, which had an AUC of 0.61, with 42% sensitivity and 86% specificity. In addition, LC-SPIK accurately detected the presence of HCC in more than 70% of HCC patients with false-negative AFP results. DISCUSSION: The study provided strong evidence that LC-SPIK detects HCC, including early-stage HCC, with high sensitivity and specificity, and might be useful for surveillance in cirrhotic and chronic HBV/HCV patients, who are at an elevated risk of developing HCC.

211 Background: Cancer patients have many medical and psychosocial needs, which may increase during the coronavirus pandemic and may be difficult to identify or address in the absence of in-person patient visits. We sought to (1) risk stratify hematology/oncology patients using general medicine and cancer-specific methods to identify those at high risk for acute care utilization, (2) measure the correlation between risk-stratification methods, and (3) perform a phone-based needs assessment with intervention for these patients. Methods: Patients were risk-stratified using a general medical health composite score (HCS) embedded in the electronic medical record, and a cancer-specific risk (CSR) stratification based on disease and treatment characteristics. The correlation between HCS and CSR was measured using Spearman’s correlation. A multi-disciplinary team developed a focused needs assessment script with recommended interventions for patients categorized as high-risk by either method. The number of patient needs identified and referrals for services made in the first month of outreach are reported. Results: 1,421 patients were risk stratified, with 15% high-risk using HCS and 21.2% high-risk using CSR. Overall correlation between HCS and CSR was modest (r = 0.39). During the first month of the pilot, 287 patients were called for outreach with 245 contacted (85%). Commonly identified needs were financial difficulties (17%), uncontrolled symptoms (15%), and interest in advance care planning (13%), resulting in referral for supportive services for 33% of patients. Conclusions: There is a high burden of unmet medical and psychosocial needs in hematology/oncology patients during the coronavirus pandemic. A phone-based outreach program results in identification of and intervention for these needs, however additional cancer-specific risk models are needed to improve targeting to high-risk patients. This process can serve as a framework for other institutions wishing to implement similar outreach programs during this pandemic. [Table: see text]

Importance Despite requirements of informed consent, patients with advanced cancer often receive palliative chemotherapy (PC) without understanding that the likelihood of cure is remote. Objective To determine whether a PC educational video and booklet at treatment initiation could improve patients’ understanding of its benefits and risks. Interventions Regimen-specific PC videos and booklets presenting information about logistics, potential benefits, life expectancy (optional), adverse effects, and alternatives. Videos featured authentic patients sharing diverse experiences. After receiving treatment recommendations, research assistants distributed materials to patients for independent review. Design, Setting, and Participants Multicenter randomized clinical trial of patients with advanced colorectal or pancreatic cancer starting first-line or second-line PC in 5 US cancer centers with enrollment from June 2015 to September 2017 and follow-up to December 2019. Main Outcomes and Measures The primary outcome was accurate expectations of chemotherapy benefits at 3 months, defined as responding “not at all likely” to “What is your understanding of how likely the chemotherapy is to cure your cancer?” (from the Cancer Care Outcomes Research and Surveillance study). Secondary outcomes included understanding of adverse effects, decisional conflict (SURE test), regret (Decisional Regret Scale), and distress (Functional Assessment of Cancer Therapy–General emotional well-being subscale). Results Among 186 patients with advanced colorectal or pancreatic cancer who were starting first-line or second-line PC (94 randomized to usual care, 92 to intervention; mean [SD] age, 59.3 [12.6] [range, 28-86] years; 107 [58%] male; 118 [63.4%] colorectal and 68 [36.6%] pancreatic cancer), most patients wanted “a lot” of information or “as much information as possible” about adverse effects (149, 80.1%), likelihood of cure (148, 79.6%), and prognosis (148, 79.6%). Among the intervention arm, 59 (78%) reviewed the booklet and 30 (40%) reviewed the video within 2 weeks. The primary outcome did not differ between intervention and control arms (52.6%; 95% CI, 40.3%-65.0%; vs 55.5%; 95% CI, 45.1%-66.0%). Accurate adverse effect understanding was more common among intervention than control patients (56.0%; 95% CI, 44.3%-67.7%; vs 40.2%; 95% CI, 29.5%-50.9%;P = .05), although this did not meet the threshold for statistical significance. The intervention did not increase distress, despite frank prognostic information. Other secondary outcomes were similar. Conclusions and Relevance Provision of an educational video and booklet did not alter patients’ expectation of cure from PC. Alternative delivery strategies, such as integration with nurse teaching, could be explored in future studies. Trial Registration ClinicalTrials.gov Identifier:NCT02282722

7067 Background: Treatment effects may differ between trials and community settings, in part due to underrepresentation of certain patient subgroups in trials. We used a hybrid approach combining clinical trial and real-world data to compare the effectiveness of adjuvant FOLFOX vs 5FU for stage II-III colon cancer in community oncology practice. Methods: We used Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer (MOSAIC) combined with patients who met trial eligibility criteria within US Oncology from 1/1/2008-5/31/2019. In the combined data, we used logistic regression to estimate the probability of trial enrollment as a function of age, sex, substage, body mass index (BMI), and performance status. We estimated inverse odds of sampling weights and weighted MOSAIC participants to reflect three US Oncology populations: 1) patients meeting trial eligibility, 2) stage III patients, and 3) stage III patients initiating FOLFOX. Within the weighted trial populations, we estimated mortality hazard ratios (HRs) and bootstrapped 95% confidence intervals (CIs) comparing FOLFOX with 5FU. Results: There were 2246 MOSAIC participants and 9335 US Oncology patients. MOSAIC participants were younger, had more stage II cancer, lower BMI, and worse performance status compared with US Oncology patients. After weighting MOSAIC participants to reflect the US Oncology populations, the HRs were attenuated (Table) compared with the original MOSAIC estimate (HR = 0.84; 0.71,1.00). Conclusions: When differences between trial and clinical populations exist and response to therapy varies across subgroups, treatment efficacy can differ from clinical effectiveness. Compared with trial results, we found that effectiveness of FOLFOX versus 5FU was attenuated in community oncology practice. [Table: see text]

3522 Background: Adjuvant chemotherapy regimens take months to complete. Despite this, trials and observational studies evaluate chemotherapy adherence via measures assessed at the end of treatment (e.g. number of patients missing any dose, relative dose intensity [RDI]). This approach misses information that impacts outcomes, like treatment delays. We propose longitudinal cumulative dose (LCD) as a way to integrate the impact of dose reductions, missed doses, and dose delays at each cycle over time. Methods: We obtained data from the 2,246 participants in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer (MOSAIC). We evaluated proportions of patients stopping treatment early and reducing (based on protocol), missing, or delaying a dose in each arm for each chemo agent at each visit. We obtained LCD, the fraction of the final standard dose a participant reached by a given day, for each participant and each chemo agent. We compared LCD medians over time and at the end of a standard regimen (24 weeks) between treatment arms and by age and performance status. We assessed agreement between oxaliplatin LCD and RDI with Fleiss’ kappa (Table). Results: Participants randomized to FOLFOX were more likely than those randomized to 5FU to stop treatment, reduce doses, miss doses, or delay visits; these differences increased over time. Median LCD for oxaliplatin in the FOLFOX arm at 24 weeks was 77%. Graphs of median LCD for 5FU showed a clear difference between arms (FOLFOX arm median LCD: 81%; 5FU arm median LCD, 96%). While 5FU LCD decreased with age in the FOLFOX arm (median LCD in those age

Background: F. nucleatum is an oral anaerobe aberrantly found in up to 43% of CRCs. F. nucleatum presence is associated with additional known prognostic variables, including BRAF mutation and immune infiltration. In nonmetastatic CRC, F. nucleatum is associated with post-chemotherapy recurrence and inferior cancer-specific survival. However, the prognostic value of F. nucleatum in mCRC is not well described. We evaluated the association between F. nucleatum, integrated with other significant prognostic clinicopathologic factors, in a prospective clinical trial cohort of mCRC. Methods: LCCC1029 was a 2:1 randomized phase II trial of 2nd-line chemotherapy with 5-fluorouracil/irinotecan plus either regorafenib or placebo in mCRC. DNA and RNA were extracted from FFPE archival tumor samples, and quantitative PCR to measure F. nucleatum levels was successfully performed on 73 of those samples. We compared PFS and OS using Kaplan-Meier method and log-rank tests, and univariate and multivariate hazard ratios (HR) were estimated using Cox proportional hazards method. Results: Among the 73 mCRC patients with F. nucleatum quantitated, 20 (27%) had a high level and 53 (73%) had undetectable or low levels of F. nucleatum. On univariate analysis, F. nucleatum high level was not associated with PFS (HR 0.78, 95% CI 0.46-1.33; log-rank p=0.36) or OS (HR 0.83, 95% CI 0.46-1.51; log-rank p=0.54). However, the F. nucleatum positive subgroup trended toward higher rates of BRAF mutation (12%, vs 2% in F. nucleatum low/negative), KRAS/NRAS mutation (47% vs 27%), and MSI-High (12% vs 5%). We thus performed multivariate analyses of PFS and OS including F. nucleatum high level, BRAF mutation, KRAS/NRAS mutation, MSI, prior antiangiogenic therapy, and age on the subgroup of 58 patients who had results from all platforms. On multivariate analysis, high F. nucleatum expression trended toward association with improved PFS, with HR 0.57 (0.30-1.10, p=0.095). BRAF mutation, prior antiangiogenic therapy, and F. nucleatum were significantly associated with improved OS, with high F. nucleatum expression having adjusted HR 0.48 (0.23-0.99, p=0.048). Conclusions: Expression of F. nucleatum in the tumor of patients with mCRC was significantly associated with improved OS in mCRC. While results need to be validated, these findings suggest that F. nucleatum is associated with prognosis in a context-dependent fashion and may confer differential prognosis in nonmetastatic versus metastatic CRC patients. Citation Format: Michael S. Lee, Temitope O. Keku, Amber McCoy, Sara R. Selitsky, Joel Parker, Todd Auman, Kelli Hammond, Sushant A. Patil, Ganiraju Manyam, Scott Kopetz, Hanna K. Sanoff, Federico Innocenti. Association of Fusobacterium nucleatum (F. nucleatum) with progression-free survival (PFS) and overall survival (OS) with 2nd-line FOLFIRI +/- regorafenib in metastatic colorectal cancer (mCRC) [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A03.

196 Background: LCCC1029 was a 2:1 randomized phase II trial of 2nd-line FOLFIRI plus either regorafenib or placebo in mCRC. The addition of regorafenib improved PFS (median PFS 6.1 vs 5.3 mo, HR 0.73, 95% CI 0.53-1.01). However, the effect of somatic mutations on regorafenib activity has not been tested. Methods: We performed whole exome sequencing on archival primary tumor tissue and paired normal tissue in 85 patients of LCCC1029. We compared PFS and OS using Kaplan-Meier method and log-rank tests, and hazard ratios (HR) were estimated using Cox proportional hazards method. Results: Among the 85 subjects, 54 (64%) had tumors wild-type (WT) for KRAS and BRAF, 26 (31%) had tumors with KRAS mutations in exons 2-4, and 5 (6%) had tumors with BRAF V600E. The addition of regorafenib to FOLFIRI improved PFS in the KRAS/ BRAF WT subgroup (median PFS 8.0 vs 4.9 mo, HR 0.68, 95% CI 0.48-0.97, log-rank p=0.028), but not in the KRAS mutant subgroup (median PFS 6.8 vs 5.5 mo, HR 0.90, 95% CI 0.61-1.35, log-rank p=0.617) or the BRAF mutant subgroup (log-rank p=0.156). In all of these subgroups, the addition of regorafenib was not associated with significant difference in OS. BRAF V600E was prognostic and associated with significantly worse OS (median OS 8.4 vs 18.0 mo, HR 2.59, 95% CI 1.01-6.66, log-rank p=0.04). Conclusions: The addition of regorafenib to FOLFIRI improves PFS among the subgroup of patients with KRAS and BRAF dual WT CRC, but not among the KRAS mutant subgroup. These results indicate that the addition of anti-angiogenic therapy to second-line chemotherapy backbones may be more effective in KRAS/ BRAF WT tumors in particular. More confirmatory studies are needed to corroborate this finding.

TPS260 Background: Deficient DNA mismatch repair (dMMR) colorectal cancer (CRC) is highly immunogenic. Preclinical data showed synergistic interactions among FOLFOX, anti-VEGF, and programmed cell death-1 (PD-1) pathway blockade. Prior phase I study of mFOLFOX6/ bevacizumab (bev) + atezolizumab (atezo) was well tolerated and enhanced intratumoral infiltration of CD8+ T cells. We hypothesize that the dMMR subset of CRC may be effectively targeted with combination of PD-1 pathway blockade and mFOLFOX6/bev. Methods: This is a prospective randomized phase III open-label trial. Pts (N=347) with mCRC dMMR will be randomized to three trial arms (1:1:1): mFOLFOX6/bev; atezo monotherapy; or mFOLFOX6/bev + atezo. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Primary endpoint is progression-free survival (PFS) assessed by study investigator of mFOLFOX6/bev/atezo and atezo monotherapy compared to mFOLFOX6/bev. Secondary endpoints include OS, objective response rate, safety profile, disease control rate, duration of response, and PFS by retrospective central review. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2); availability of archived tumor tissue for central confirmation of dMMR status; and measurable disease per RECIST. Activated 11-7-17. As of 9-11-19, enrollment continues with 44/347 pts enrolled. Clinical trial: NCT02997228. Support:U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.