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209 Background: Metastatic colorectal (CRC), pancreatic (PANC), and gastroesophageal cancers are the leading causes of GI cancer–related mortality (5-y survival: 15%, 3%, and 5%-6%, respectively) (ACS 2022). HLA LOH is a recurrent mechanism of immune escape observed in 15%-20% of GI cancers (Hecht R., ASCO GI 2022). The Tmod platform is a logic-gated chimeric antigen receptor (CAR) T-cell modular system, comprising a carcinoembryonic antigen (CEA)- or mesothelin (MSLN)-targeting CAR activator and a separate HLA-A*02-targeting blocker receptor. Both in vitro/in vivo, Tmod CAR T therapy kills cells with HLA-A*02 LOH (tumor) without harming cells with retained HLA-A*02 expression (normal). However, HLA-A*02 LOH can only be therapeutically exploited if patients are identifiable through a feasible and timely clinical workflow. Methods: We established a biobanking protocol (BASECAMP-1, NCT04981119) to determine whether HLA-A*02 LOH patients can be prospectively identified. Patients with CRC, PANC, or non-small cell lung cancer (NSCLC), and a high risk for incurable relapse, were screened first using a standard HLA assay. Heterozygous HLA-A*02 positive tumor samples were then assessed for LOH using a bioinformatic algorithm applied via the Tempus xT platform. Results: As of Sep 1, 2022, 83 patients were consented at 4 institutions. HLA status was obtained from 70 patients and 28 were identified as HLA-A*02:01 heterozygous (40%; expected frequency based on USA NMDP data, 27.6%). LOH results were available for 16 patients; 4 LOH-positive patients were identified (25%, 2 PANC, 2 NSCLC). The LOH assay sensitivity declines below a tumor purity of 40% (Hecht R., ASCO GI 2022). Six patients had a tumor purity of 20% (all with PANC, a tumor known for high stromal content), limiting possible LOH detection. The impact of tumor purity on LOH sensitivity was highlighted in a patient with a low initial sample tumor purity (30%) that resulted in a 41% probability of HLA-A*02:01 LOH (below positive threshold). A second sample with a higher tumor purity (70%), obtained from formalin-fixed, paraffin-embedded sections, resulted in a 92% probability of HLA-A*02:01 LOH (positive). Conclusions: BASECAMP-1 prospective identification of HLA-A*02 LOH is feasible in the real-world setting. The frequencies of the HLA-A*02 allele and of HLA-A*02 LOH in this cohort mirrored expected population frequencies. LOH results can be obtained within a clinically feasible workflow and timeframe, although samples with a < 40% tumor purity have a reduced sensitivity for LOH detection, an issue recurrently observed in patients with PANC. The BASECAMP-1 strategy enables prospective identification of appropriate patients for future therapeutic clinical trials using Tmod CEA and MSLN logic-gated CAR T cells. Clinical trial information: NCT04981119 .

TPS657 Background: Poorly differentiated neuroendocrine carcinoma (NEC) is an aggressive malignancy comprising both pulmonary and extrapulmonary primary sites. NEC includes both small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), as well as other neuroendocrine carcinomas arising from any primary organ. A substantial portion (~40%) of NEC arises from gastrointestinal primary sites. The optimal systemic therapy beyond first line platinum and etoposide is not established. There is a critical need to improve upon the median survival in the second line, as most patients do not survive more than 6 months. The efficacy of single agent immune checkpoint inhibitors (ICIs) in NEC has been disappointing. One possible explanation for this is that the tumor microenvironment in NEC is non-inflamed. VSV-IFNβ-NIS is a vesicular stomatitis virus (VSV)-based oncolytic virus being tested in multiple early phase clinical trials. Preliminary studies of immune responses in patients receiving VSV-IFNβ-NIS therapy suggest some patients develop T cell responses to viral antigens and known tumor antigens. We hypothesize that VSV-IFNβ-NIS therapy may convert a non-inflamed or immune-excluded phenotype in NEC to a highly inflamed phenotype that sensitizes the tumor to ICIs. Methods: This is a phase 1-2 safety run-in study designed to determine the safety of VSV-IFNβ-NIS in combination with a single agent ICI, pembrolizumab, followed by dose expansion in patients with refractory non-small cell lung cancer (NSCLC) or NEC. The safety run-in portion of this study has been completed, and we are presently testing the recommended phase 2 dose (RP2D) of VSV-IFNβ-NIS in an expansion cohort of patients with SCLC or NEC of any primary site. Patients must have previously progressed on at least one line of systemic therapy. Prior treatment with checkpoint inhibitors is permitted. Patients are treated one time with the RP2D of 1.0x10^11 TCID50 VSV-IFNβ-NIS on day 1, followed by pembrolizumab on day 8 and then pembrolizumab every 21 days until progression, up to 2 years. The primary objective is to estimate the response rate by RECIST 1.1. Secondary objectives include estimation of disease-control rate, duration or response, progression-free survival, overall survival, and safety signals. The NEC expansion cohort will seek to enroll 10 patients. If at least one objective response is observed, and safety is confirmed, the regimen will be considered for future study. Clinical trial information: NCT03647163 .

9135 Background: Bronchial carcinoid (BC) is often categorized into multifocal (MBC) or solitary (SBC). MBC, excluding tumorlet and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, is considered a relatively uncommon subgroup of BC, with much of the MBC literature stemming from case reports/small series. Our study analyzes MBC among a large cohort of 569 patients with BC and argues for change to the current clinical understanding of MBC. We suggest using the term bronchial neuroendocrine tumor (bNET) to more accurately represent its cells of origin and move away from “carcinoid” (historically meaning “carcinoma-like”) and the outdated associated connotation that carcinoids all have a similar, benign clinical and biological behavior. Methods: Using the Mayo Clinic Epidemiology and Genetics of Lung Cancer Database with Institutional Review Board approval, we retrospectively reviewed 569 patients with bNET (204 males, 365 females) presenting to Mayo Clinic Rochester between 1/1997-12/2012. We used univariate and multivariate Cox regression analyses to evaluate factors affecting overall survival. Results: 80 patients (of 569, 14.1%) were diagnosed with multifocal (MbNET) and 489 with solitary (SbNET). Two-sided Fisher’s exact tests found that older age, female gender, never having smoked cigarettes, and tumorlets were associated with MbNET diagnosis. Family lung cancer history, histopathologic grading (pathology: typical vs. atypical), Ki67, and presence of syndromes (carcinoid, Cushing, and MEN1 syndromes) were similar between MbNET and SbNET groups. Most MbNET cases were stage III-IV at the time of diagnosis, while the majority of SbNET cases were stage I. 5-year OS (83%) and 5-year PFS (75%) of MbNET patients were higher than those of their SbNET counterparts (74% and 68%, respectively). Metastasis status was an independent prognostic factor of poor OS in SbNET (P

TPS2676 Background: Solid tumors comprise > 90% of cancers. Metastatic colorectal cancer, non-small cell lung cancer, and pancreatic cancer are among the leading causes of cancer-related mortality (5-year overall survival: 14%, 6%, and 3%, respectively) (ACS. 2021). Chimeric antigen receptor (CAR) T-cell therapy has demonstrated clinical efficacy in hematologic malignancies (Neelapu S. et al. N Engl J Med. 2017). Translating engineered T-cell therapies to solid tumors has proven to be challenging due to a lack of tumor-specific targets that can discriminate cancer cells from normal cells. Previous studies using carcinoembryonic antigen (CEA) T-cell receptors and mesothelin (MSLN) CARs resulted in dose-limiting on-target, off-tumor toxicities (Parkhurst M, et al. Mol Ther. 2011; Tanyi J. Cellicon Valley '21). To create a therapeutic safety window, Tmod CAR T-cell therapy utilizes dual-signaling receptors to create a robust NOT logic gate capable of killing tumor cells, while leaving healthy cells intact (Hamburger A, et al. Mol Immunol. 2020). The 2 receptors in Tmod CAR T-cell therapy comprise an activator that recognizes an antigen on the surface of tumor cells that may also be present on normal cells, such as CEA and MSLN, and a blocker that recognizes a second surface antigen from an allele lost only in tumor cells. The frequency of HLA LOH among advanced GI solid tumor cancers in the Tempus real-world dataset is 16.3% with a range of 15.6%-20.8% between colorectal, pancreatic, and gastroesophageal tumors (Hecht R. et al. ASCO-GI 2022. Abstract #190). As such, HLA LOH offers a definitive tumor versus normal discriminator target for CAR T-cell therapy. Different activator/blocker combinations can be engineered with the Tmod platform technology and may be applied to T cells and natural killer cells in autologous and allogeneic settings. BASECAMP-1 is a currently enrolling observational study with key objectives of 1) To identify patients with somatic HLA LOH eligible for Tmod CAR T-cell therapy, and 2) To obtain leukapheresis and feasibility for the future EVEREST Tmod CAR T-cell trial. Methods: BASECAMP-1 (NCT04981119) patient eligibility has 2 parts: 1) Patients will be initially screened to identify germline HLA-A*02 heterozygosity by central NGS. If HLA-A*02 heterozygosity is confirmed, primary archival tumor tissue will be analyzed for somatic mutations by xT-Onco NGS testing. 2) If the tumor demonstrates HLA-A*02 LOH and the patient is eligible after screening, the patient will undergo leukapheresis. Banked T cells will be available for the autologous EVEREST Tmod CAR T-cell therapy interventional study to reduce waiting time at relapse. Clinical trial information: NCT04981119.

TPS8604 Background: Chemoimmunotherapy followed by durvalumab maintenance yields a median overall survival of 12.9 months in patients with extensive stage Small Cell Lung Cancer (ES SCLC), which is an improvement over chemotherapy alone. However, 90% of these patients will have progressive disease. While topotecan and lurbinectedin have established modest activity in the second line, it is unknown whether continuing immunotherapy in this setting confers additional benefit. In preclinical studies lurbinectedin, a DNA minor groove binder, used with immune checkpoint inhibitors has synergistic effects. Methods: This phase 2 trial is enrolling patients with ES SCLC who have progressed on platinum based chemoimmunotherapy, to three treatment groups. Group 1 includes patients with platinum sensitive SCLC who will receive durvalumab (1500 mg given as an intravenous [IV] infusion once every 3 weeks) and topotecan (1.25 mg/m2/day IV for 5 consecutive days every 3 weeks). In Groups 2A and 2B, patients with platinum sensitive and platinum resistant disease respectively, receive durvalumab and lurbinectedin (3.2 mg/m2 IV on Day 1 of every 21-day cycle). Patients with platinum sensitive disease are assigned to Groups 1 or 2A based on the preferences of the treating physician and the patient. Patients with treated/stable CNS metastases are eligible. The primary endpoint is the proportion of patients who are alive at 6 months (6OS) for Group 1 and the proportion of patients who are alive and progression-free at 6 months (6PFS) in Groups 2A and 2B. Secondary endpoints include safety, adverse event profile, response rate, PFS, and OS. The sample size is based on a 2-stage Simon Optimal Design. For Treatment Group 1, with 22 eligible patients there is 80% power to detect a true 6-month OS rate (6OS) of 75%, with 10% alpha under the null hypothesis that the true 6OS is at most 50%. For Treatment Group 2A, with 20 eligible patients this design has 80% power to detect a true 6-month PFS rate (6PFS) of 65%, with 10% alpha under the null hypothesis that the true 6PFS is at most 40%. For Treatment Group 2B, with 22 eligible patients this design has 80% power to detect a true 6-month PFS rate (6PFS) of 40%, with 10% alpha under the null hypothesis that the true 6PFS is at most 19%. To account for possible drop-outs, accrual targets will be 24, 22, and 24 patients to Groups 1, 2A, and 2B respectively. For the safety analyses, 6 patients will be enrolled at the starting dose level for each treatment group (1, 2) and then briefly closed to accrual to assess adverse events. If we observe 2+ DLTs in these 6 treated patients during Cycle 1 within a treatment group (1 vs. 2), we will declare the combination treatment too toxic and lower the starting dose of chemotherapy for the next 6 patients. The study was open for all 3 groups as of January 2022 and has accrued 2 patients. Clinical trial information: NCT04607954.

190 Background: Metastatic colorectal (CRC), pancreatic (PANC), and gastroesophageal (GE) cancers are the leading causes of GI cancer–related mortality (5-yr survival rate, 14%, 3% and ̃5-6%, respectively). T-cell immunotherapy targeting GI-associated tumor antigens has been attempted, but efficacy has been constrained by on-target off-tumor toxicity, limiting the therapeutic window. The Tmod (TM) platform is an AND-NOT logic-gated CAR T modular system, versions of which have a CEA- or MSLN-targeting CAR activator and a separate HLA-A*02-targeting blocker receptor to protect normal cells. Tmod CAR T exploits HLA LOH, common in GI malignancies (10-33% in primary solid tumors [TCGA]) and can kill tumor cells without harming healthy cells in vitro and in vivo. However, the prevalence of HLA LOH across GI tumors is unknown in the real-world setting. We utilized the Tempus xT oncology NGS database of patients with multiple GI tumors. From a standard-of-care NGS assay, GI cancer patients can be readily identified for HLA LOH and future treatment with Tmod CAR T therapy. Methods: The occurrence of HLA LOH in GI tumors of 1439 patients was assessed using paired germline and somatic DNA sequencing using a research assay [6]. CRC, PANC and GE patients with ≥ stage 3 were then extracted, and rates of HLA LOH were identified (ie, whether loss occurred across high-frequency HLA-A alleles). In addition, mutations in KRAS and BRAF, as well as MSI status were stratified to determine any association with HLA-A LOH. Results: HLA-A LOH was detected in 830 (17.3%) of all solid tumor records, and a similar proportion when all GI cancer records were analyzed (17.0%). For GI subtypes, these values ranged from 13.5% to 23.1% (Table). No high-frequency HLA-A allele (A*01, A*02, A*03, A*11) was more likely to be lost. Clinical biomarkers ( KRAS, BRAF and MSI status) were not associated with HLA-LOH. Conclusions: The frequency of HLA LOH among advanced solid tumor cancers in this dataset is 17.3%, with a range of 13.5-23% between CRC, PANC and GE. The HLA LOH frequency observed in these GI tumors is consistent with that in primary tumors from TCGA, which also used germline-matched and tumor samples. Clinical biomarkers were not associated with HLA LOH. Tempus NGS was able to identify HLA LOH, which can be used for Tmod CAR T therapy to an enhanced therapeutic window. Identification of these patients in BASECAMP-1 (NCT04981119) will enable novel Tmod CAR T therapy. [Table: see text]

e20554 Background: The paradigm for locally advanced non-small cell lung cancer has been markedly altered to include maintenance durvalumab (D) post completion of definitive chemoradiation (CRT) following the publication of the Pacific trial in 2018. The toxicity of this treatment has not been well evaluated in the real-world setting. Methods: We identified 42 patients (pts) with Stage IIB-IIIC NSCLC treated at Mayo Clinic Rochester between 6/1/2018 and 10/1/2020 who received definitive CRT followed by maintenance D. Data were abstracted by retrospective chart review under an IRB approved protocol. Results: Median age was 66 yrs (range 47-90) and 62% were women. Primary lung cancer histology included 19 adenocarcinoma, 20 squamous cell, and 3 adenosquamous. The distribution of stages was: IIB (4/42), IIIA (15/42), IIIB (19/42), IIIC (4/42). Approximately half of patients had PDL1 expression > 25% (20/42). With a median follow up of 12.2 months (calculated from first cycle of D; range 4.2-30.5 months), 14 had completed one year of maintenance D, 16 were receiving ongoing D, and 10 stopped D early with 6/12 discontinuing due to disease progression (4/6 local progression, 2/6 distant progression). Other reasons for discontinuation (5/10) included grade 3 colitis, grade 2 hepatitis, aspergillus lung infection, and flare of autoimmune disorders. One quarter of patients experienced grade 2 radiation pneumonitis (RP; 10/42) with median time to development of RP 78 days from end of CRT and 45 days from start of D. RP was determined by multidisciplinary review of imaging and treatment fields. 17/42 patients developed immune related adverse events (see Table for details). There was minimal overlap between the patients who experienced pneumonitis and immune related toxicity; 2/17 had both pneumonitis and immune related toxicity (hepatitis, thyroiditis). Conclusions: In our early experience with the Pacific regimen, 29% of patients did not complete D due to either toxicity or progression during D administration. Pneumonitis was common (10/42 patients) although there were no grade 3 events. Nearly half of the patients developed an immune-related adverse event. Further analysis is needed to evaluate the real-world toxicity of this treatment as well as oncologic outcomes.[Table: see text]

9093 Background: Treatment addressing non-small cell lung cancer (NSCLC) harboring EGFR or HER2 exon 20 insertion mutations remains an unmet need. These tumors are associated with a high incidence of CNS metastases and unfavorable survival rates. Poziotinib is a potent, irreversible, tyrosine kinase inhibitor (TKI) with a structure that can overcome the steric hindrance of the exon 20 limited binding pocket. Preclinical data suggest poziotinib CNS penetration, and here we show meaningful poziotinib CNS activity in patients with NSCLC harboring exon 20 insertion mutations in an ongoing multi-cohort, multi-center Phase 2 study (ZENITH20; NCT03318939). Methods: ZENITH20 enrolled previously treated and naïve patients with advanced/metastatic NSCLC and EGFR or HER2 exon 20 insertion mutations in several cohorts: Cohort 1 (C1) EGFR previously treated; Cohort 2 (C2) HER2 previously treated and Cohort 3 (C3) EGFR treatment-naïve. All patients with stable CNS metastases at baseline were included. Poziotinib (16 mg) was administered orally QD, with follow-up for up to 24 months. The primary endpoint was Objective Response Rate (ORR) evaluated centrally using RECIST v1.1 by an independent image review committee. Secondary endpoints included Disease Control Rate (DCR), Duration of Response (DOR), Progression-Free Survival (PFS) and safety. Primary efficacy results have been previously released. Intracranial response was determined based on the modified RECIST criteria. Results: A total of 284 patients across 3 cohorts (C1 n=115; and C2 n=90; and C3 n=79) with a median age of 60.5 years were enrolled. The median follow-up was 7.3, 8.3, and 9.2 months for all patients in C1, C2, and C3, respectively. In NSCLC patients that had baseline CNS lesions (N=36), the analysis showed a patient-based ORR of 22.2% (8/36) and a DCR of 88.9% (32/36). One patient in each cohort had a complete intracranial response and stable disease was 80.6% across 3 cohorts and 92.9% in C2. Two patients each in C1 and C3 had progressive disease (PD) and none had CNS progression in C2 (Table). Conclusions: Poziotinib exhibited clinically meaningful CNS activity in patients with EGFR or HER2 exon 20 mutations in ZENITH20 Cohorts 1-3. The majority of the patients had no CNS progression and 3/36 patients had intracranial complete responses. The preliminary data suggest that poziotinib may provide a meaningful treatment alternative for patients with NSCLC that harbor EGFR or HER2 exon 20 mutations and who present with CNS metastases that have poor prognosis. Clinical trial information: NCT03318939. [Table: see text]

e21007 Background: There is a lack of data to guide the management of resectable bronchopulmonary carcinoid tumors (BCTs). Methods: The NCDB database was retrospectively reviewed to analyze the roles of surgery, chemotherapy and radiation. Patients with a diagnosis of clinically staged T1-2/N0-1 typical carcinoid (TC) and atypical carcinoid (AC) between 2004-2012 were included. Kaplan-Meier methods and multivariable analysis were performed. Results: A total of 2148 patients (TC 1874 & AC 274; T1/1648 & T2/500) were identified. The median age was 59 (range 18-89). There was a female (69.7%) and right lung (56.9%) predominance. Fifty-three patients received pneumonectomy, 68 chemotherapy, and 84 radiation therapy. The impact of age, histology (TC vs. AC), medical comorbidities (Charlson/Deyo score 0 vs. ≥1) and type of surgery [sublobar resection (SR) vs. lobectomy vs. lobectomy with mediastinal lymph node dissection (L/MLND)] were subsequently examined. AC, older age, and comorbidities were associated with shorter overall survival (OS) by both univariate and multivariable analysis. Patients who underwent lobectomy had longer OS (119 months) than those with SR (109 months) or L/MLND (115 months). However, this association was not significant by multivariable analysis with age incorporated as either a categorical ( < 60 vs. ≥60) or a continuous variable (Table). In the subgroup analysis of patients with T1, T2, TC and AC respectively, type of surgical resection was not significantly associated with OS by multivariable analysis. Conclusions: Patients with resectable BCTs have excellent OS. Atypical histology, older age, and comorbidities predicted inferior OS. There were insufficient data to support the use of perioperative chemotherapy or radiation therapy. Lobectomy was associated with prolonged OS by univariate analysis but this was not significant in the multivariable model, suggesting that SR is a reasonable approach for patients who cannot tolerate lobectomy. MLND did not seem to provide additional survival benefits. [Table: see text]

e21575 Background: The clinical significance of brain metastases in patients with bronchopulmonary neuroendocrine (NE) tumors is unknown; we therefore conducted a population based analysis to evaluate the implications of brain metastases in these patients. Methods: The NCDB database was queried to identify patients with stage IV bronchopulmonary NE tumors treated between the years of 2004-2012. Patients were split into two groups based on the presence of brain metastases at diagnosis and survival probabilities with multivariate models were performed. Results: A total of 7,725 patients with Stage IV bronchopulmonary NE tumors were identified. The histological subtypes studied in this cohort were NE carcinoma (65.4%), large cell NE carcinoma (30.5%), typical carcinoid (2.8%) and atypical carcinoid (1.3%) . The patients included in this study were mainly white (86.4%) men (56.8%) with a median age of 67 years who had liver (9.5%), bone (6.2%) and brain (5.9%) metastases at diagnosis. The median overall survival (OS) of the cohort was 5.59 (95% CI: 5.4-5.8) months, but when OS was stratified by histological subtype it was significantly better in patients with typical carcinoid (table). In the whole cohort, the median OS did not differ between patients with and without brain metastases (5.55 vs. 5.68; p = 0.24). However, a sensitivity analysis by histology showed that the presence of brain metastases worsen the median OS of patients with typical carcinoid only (15.1 vs 4.6, p = 0.04). An adjusted multivariate analysis restricted to patients with brain metastases showed that administration of systemic chemotherapy (HR:0.5; 95% CI:0.35-0.72, p < 0.001) and resection of distant metastases (HR:0.5; 95% CI:0.29-0.88, p = 0.017) were the two most powerful independent prognostic factors. Conclusions: The presence of brain metastases negatively impact survival of patients with typical carcinoids but not in those with the other histological subtypes included in this study. Staging MRI should be strongly considered at diagnosis in patients with bronchopulmonary NE tumors, due to the sizable proportion of these patients presenting with brain metastases and also due to its prognostic value in a subset of this population. [Table: see text]

7059 Background: Preliminary data suggests that immune-related adverse events (irAEs) are associated with lower all-cause mortality, presumably due to improved anti-tumor responses. Investigations of large cohorts are needed to establish better understanding of that association. Methods: We reviewed the Mayo Clinic database for all patients who received an immune checkpoint inhibitor (ICI). The primary outcome was all-cause mortality. Descriptive and uni-variate analyses were generated. Results: Between March, 2010 and July, 2019, 3,326 patients received an ICI. The most common irAEs were colitis (287, 8.6%), pneumonitis (238, 7.2%) and hepatitis (227, 6.9%). A total of 933 (28.1%) patients developed at least 1 irAE and 176 (5.3%) patients experienced 2 or more irAEs. Survival analysis demonstrated an association between the number of irAEs and all-cause mortality (log-rank, P < 0.0001), a relationship which was maintained for the 3 most common cancer types (lung, melanoma, renal) and for the individual ICI agents. In patients with lung cancer, colitis (P = 0.04) but not pneumonitis (P = 0.83) was associated with improved overall survival. No association between irEA and all-cause mortality was demonstrated in patients with history of stroke (log-rank, P = 0.12), peripheral artery disease (PAD) (log-rank, P = 0.68) and obesity (log-rank, P = 0.18). In an analysis of pre-ICI body-mass index (BMI), an association between irAE and lower overall mortality was shown in patients with BMI < 30 (log-rank, P < 0.001) and not in those with higher BMIs (log-rank, P = 0.09). The presence of stroke, PAD and obesity were associated with higher all-cause mortality in a survival analysis (P < 0.001). The irAE-mortality association was not modulated by the presence hypertension (log-rank, P < 0.0001), diabetes mellitus (log-rank, P < 0.0001), or heart failure (log-rank, P = 0.006). Conclusions: The development of any irAE is associated with higher overall survival. The presence of numerous cardiovascular disease states neutralizes that association, likely a result of competing causes of mortality although interaction with immune or inflammatory pathways is possible. In addition, pneumonitis is not associated with better overall survival in patients with lung cancer presumably due to compromise of already-tenuous respiratory status.

82 Background: Use of immune checkpoint inhibitors (ICI) in metastatic solid malignancies can occasionally result in a complete response (CR). There is limited long-term data regarding outcomes for patients who achieve a CR on ICIs. Methods: We screened the Mayo Clinic electronic medical record using an institutional database query program to identify patients whose records contained keywords such as “pembrolizumab” and “complete response” or “no evidence of disease.” Patients were included if they had measurable metastatic solid tumor disease prior to initiation of ICI and if they had a CR defined by two consecutive imaging studies at least twelve weeks apart. Exclusion criteria included oligometastatic disease treated with locoregional therapy or presence of a second confounding malignancy. Results: One-hundred four patients with a CR on pembrolizumab met criteria. Most (71.1%) patients had melanoma and 63/103 (61.2%) received had received the ICI during the first line of metastatic systemic therapy. Additional characteristics are in Table. At a median follow-up of 35.8 months (6.1-87.7), patients had received ICI for a median of 12.1 months (1.5-46.7). The vast majority of patients who stopped ICI did so electively (for reasons other than disease progression). Of 88 elective discontinuations, only 7 patients had disease recurrence after a median follow-up from start of ICI of 40.5 months. Conclusions: Patients with a metastatic solid malignancy who achieve a CR to pembrolizumab appear to maintain remissions off therapy, with low rates of relapse. Further outcomes will be explored, including analyzing and characterizing a sub-group of “hyper-responders” and patients receiving other ICI agents. [Table: see text]

144 Background: Small cell lung cancer (SCLC) is highly responsive to cytotoxic therapy and can be cured in early stages of disease. In this setting, disparities in patient refusal despite provider recommendations are unknown. Methods: All incident limited stage (LS)-SCLC cases from the National Cancer Database were identified from 2004 to 2014. Logistic regression was used to determine factors associated with treatment refusal. Results: 65,664 patients (pts) were identified with LS-SCLC: 44% male, median age 68 years. 3.4% of pts refused radiation and 3.8% refused chemotherapy. The proportion of chemotherapy refusal increased over the study period: 3% in 2004-2006 compared to 5.4% in 2013-2014 [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.55-2.01]; this was not observed for radiation. In multivariate analysis, women were more likely to refuse radiation (OR 1.18, 95% CI 1.06-1.32) and chemotherapy (OR 1.30, 95% CI 1.19-1.43) than men. Women who accepted treatment had higher overall survival compared to those who refused radiation (19.8 vs 5.2 months) or chemotherapy (17.4 vs 3.9 months) (both p < 0.001). Hispanic, Black, and Asian pts were not more likely to refuse treatment than White pts. Older pts were more likely to refuse radiation (OR 1.09 per year, 95% CI 1.08-1.09) and chemotherapy (OR 1.10 per year, 95% CI 1.09-1.11). Charlson comorbidity index (CCI) of 2 was associated with more frequent treatment refusal compared to CCI of 0 (radiation OR 1.96, 95% CI 1.68-2.30; chemotherapy OR 1.54, 95% CI 1.34-1.76). Medicaid as primary insurance predicted a higher risk of refusal compared to private insurance for radiation (OR 2.36, 95% CI 1.81-3.07) and chemotherapy (OR 2.23, 95% CI 1.78-2.80). Treatment at an academic facility predicted a lower risk of radiation refusal (OR 0.71, 95% CI 0.59-0.84) but not chemotherapy refusal. Conclusions: Female sex, comorbidities, and Medicaid insurance were predictors of treatment refusal in LS-SCLC, suggesting that socioeconomic and sex disparities may affect treatment decisions in this life-threatening disease. Further research to identify reasons for refusal via patient and provider interviews can improve care of vulnerable populations with potentially curable cancer.

e20639 Background: Multiple randomized controlled trials (RCTs) have shown a robust benefit of immunotherapy with immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). We did a meta-analysis to examine the benefit of ICI in various subgroups. Methods: PubMed was searched up to Jan 15, 2019 for RCTs comparing overall survival (OS) between ICI and control (without ICI) arms. Pooled hazard ratio (HR) and 95% confidence interval (CI) was calculated for each subgroup. Interaction tests were done to compare relative benefit between opposed subgroups of interest (eg. men vs women; reported as Pheterogeneity). All analyses were performed with a random effects model in Comprehensive Meta Analysis (v2). Results: Twelve phase 2/3 RCTs involving 7244 patients were included. A significant OS benefit of ICI was found in both squamous and non-squamous histology. Current/former smokers, EGFR wild-type, and KRAS mutant patients had a significant OS benefit from ICI, but never smokers, EGFR mutant, and KRAS wild-type patients did not. An OS benefit of ICI was found in patients with or without baseline brain metastasis, PD-L1 < 1% or ≥1%, men or women, age < 65 or ≥65, and ECOG PS 0 or ≥1. No significant difference of relative benefit from ICI over control was found in patients with different PD-L1 expression, sex, age, or ECOG PS (Table). Conclusions: OS benefit of ICI in NSCLC was associated with a smoking history, wild-type EGFR or KRAS mutation. However, the OS benefit of ICI was seen regardless of histology, PD-L1 expression, sex, age, and ECOG PS. [Table: see text]

e20077 Background: Small cell lung cancer (SCLC) accounts for about 10% to 15% of lung cancers among women and men. Though heavily associated with smoking, its incidence in women is rapidly increasing despite a decline in cigarette exposure. Given the changing demographics of SCLC and hormonal factors associated with other forms of lung cancer, we studied differences between sexes in SCLC. Methods: Utilizing the National Cancer Database, we identified all incident SCLC cases from 2004 to 2014. Patients were classified as limited stage (LS) or extensive stage (ES). Women were stratified by menopausal status (≥55 years = postmenopausal). Kaplan-Meier method and Cox regression were used for overall survival (OS) and multivariable analysis. Results: 161,978 patients were identified. No significant sociodemographic differences were observed between sexes. The majority of patients were non-Hispanic whites (89.1%), followed by non-Hispanic blacks (7.5%). Men were more likely to be diagnosed with ES disease than women (63% vs. 56%). Both sexes initiated treatment within a similar time frame from diagnosis (chemotherapy, median: 18 days, IQR 8-32). Women had better median OS compared to men in both LS (15.2 vs. 12.7 months, HR: 0.85, 95% CI 0.83-0.86, p < 0.0001) and ES (6.4 vs. 5.7 months, HR: 0.88, 95% CI 0.87-0.90, p < 0.0001). No racial or ethnic disparities in OS were observed, overall and when examined within sex and disease stage groups. Differences between sexes in OS were also observed when comparing patients within the same racial/ethnic group (women having better OS). When divided by menopausal status, postmenopausal women with LS and ES had worse OS than premenopausal women (14.7 vs. 22 months, HR: 1.50, 95% CI 1.44-1.56; 6.1 vs. 9.8 months, HR: 1.41, 95% CI: 1.37-1.46, respectively). We also observed worse OS in older men when divided by age ( < 55 years and ≥55 years). In multivariable analysis, older age, postmenopausal status, and Medicaid as primary insurance were associated with worse OS for both LS and ES. Conclusions: In this large cohort, women with SCLC had better OS compared to men. Post-menopausal women had worse OS compared to pre-menopausal women. Since older men had a similar trend of worse survival compared to younger men, age might exert a more significant influence on survival than hormonal status in SCLC. Further studies with data on sexual hormone levels are necessary to better understand their role in women with SCLC.

e16162Background: Platinum/etoposide doublet is considered standard 1st-line therapy for PD NEC, however evidence to guide treatment beyond 1st-line regimens is lacking. Second-line small cell lung...

10109Background: Early integration of Palliative Care (PC) improves survival in stage IV non-small cell lung cancer (NSCLC). Here we explore patterns in PC utilization in this group. Methods: We qu...

e20543Background: Loss of ATRX, a transcriptional regulator, has been associated with reduced survival in patients with pancreatic neuroendocrine tumors. We aimed to evaluate the prognostic role of...

TPS4139Background: Peri-operative chemotherapy with 5FU, oxaliplatin and docetaxel (FLOT) is a new standard of care in resectable gastro-oesophageal adenocarcinoma (GOA), however with 3y survival r...

9065 Background: BRG is a potent and selective ALK inhibitor with preclinical and clinical activity against wild-type ALK and a broad range of mutants associated with clinical CRZ resistance, including G1202R. Herein we examine the association between BRG efficacy and ALK mutation status using plasma specimens from the initiation of BRG treatment (baseline [BL]) and the end of BRG treatment (EOT) in CRZ-resistant ALK+ NSCLC pts enrolled in the BRG Ph1/2 or pivotal Ph2 (ALTA) trials. Methods: Plasma samples were analyzed using the Resolution Bioscience ctDx Lung Panel v3.0. BRG activity was described using the confirmed objective response rate (cORR) (RECIST v1.1). Data are reported as of May 31, 2016 for the Ph1/2 (NCT01449461) and ALTA (NCT02094573) trials. Results: Of 291 CRZ-resistant ALK+ NSCLC pts enrolled in the Ph1/2 (N = 69) and ALTA (N = 222) trials, evaluable plasma samples were obtained from 67 pts at BL. cORR to BRG in these pts was 49% (33/67). An ALK fusion was detected in plasma in 45% (30/67) of these pts (cORR 57% [17/30]), of whom 33% (10/30) had secondary ALK mutations (cORR 50% [5/10]) and 67% (20/30) did not (cORR 60% [12/20]). Best responses in pts with secondary ALK mutations were: 2 CR (ALK amplification [Amp] copy number [CN] = 10; T1151M); 3 PR (L1196M; E1408V; Amp CN = 6); 4 SD (L1196M; E1419K; F1174C; C1156Y+S1206F+G1269A); 1 PD (T1151R+C1156Y+E1161D+F1174L). Of 67 pts with evaluable plasma at BL, 35 discontinued BRG therapy, of whom 20 had evaluable samples collected at EOT. No new mutations were detected at EOT in 75% (15/20) of pts. Complex mutation patterns were associated with resistance in the remaining 25% (5/20): High-level ALK-Amp (CN = 58); ALK-Amp (CN = 14)+MET-Amp (CN = 6); ALK-S1206F+S1206C+Amp (CN = 6); ALK-G1202R+L1196M+L1198Q; ALK-G1202R+BRAF-V600E+KRAS-G12D. Conclusions: ALK fusions were detected in plasma in < 50% of CRZ-resistant ALK+ NSCLC pts. BRG had substantial activity in ALK fusion–positive pts with a range of CRZ-resistance mutations. Neither primary nor secondary resistance to BRG was associated with any single plasma ALK mutation. The therapeutic implications of complex secondary resistance patterns associated with BRG require further exploration. Clinical trial information: NCT01449461, NCT02094573.

9090 Background: We identified factors associated with better OS for previously treated, PD-L1–expressing advanced NSCLC using data from KEYNOTE-010 (NCT01905657; Herbst et al. Lancet. 2016;387:1540-50), in which pembrolizumab had superior OS over docetaxel. Methods: 1033 patients were randomly assigned 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or docetaxel 75 mg/m2 Q3W. Response was assessed per RECIST v1.1 by independent central review. Multivariate analyses were performed using a Cox proportional hazards regression model on OS in the pembrolizumab arms. A set of variable selection methods was applied to 19 baseline demographic and disease characteristics, including smoking status, and identified 7 factors that contributed to OS. Data cut was September 30, 2016. Results: Adjusted hazard ratios (HRs) for the factors in the pembrolizumab arm from the model are shown in the Table. Updated OS with an additional 6 months of follow-up from this data lock for KEYNOTE-010 will be presented. Conclusions: While the overall result of KEYNOTE-010 revealed improved OS with pembrolizumab compared with docetaxel in previously treated patients with PD-L1–positive advanced NSCLC, exploratory, post hoc multivariate analyses showed that some laboratory and tumor characteristics such as nonsquamous histology, normal baseline lactate dehydrogenase (LDH), PD-L1 TPS ≥50%, and wild-type EGFR mutation status were associated with better OS among patients treated with pembrolizumab. Clinical trial information: NCT01905657. [Table: see text]

8549 Background: Bronchial carcinoid tumors are a rare group of neoplasms that usually have an indolent clinical behavior. Surgical resection is the main treatment modality for patients with early stage disease, however it is unclear if lobectomy with mediastinal lymph node dissection (L) is superior compared to partial lobectomy (PL). Methods: Utilizing the National Cancer Database from 2004-2012, 1551 patients diagnosed with T1N0 or T2N0 typical carcinoid tumors (CT), and 167 atypical carcinoid tumors (ACT), who underwent L or PL (segmental or wedge resection) as initial treatment strategy, and did not receive chemotherapy or radiation were identified. All patients had pathologically confirmed diagnosis, negative surgical margins, and complete follow up data. Overall survival (OS) was analyzed utilizing Kaplan-Meier curves, and log-rank tests were used for statistical comparisons. Cox proportional hazards were performed to control for age, sex, race, grade, year of diagnosis, Charlson/Deyo Score, insurance, income, and facility type. T-test was used to compare post-surgical hospital stay. Results: The entire cohort median age was 61 years (range 18-90), and male to female ratio was 0.43. 75% of patients with CT and 78% of ATC underwent L. The 90 day mortality following surgery was < 1 % in both surgical groups. Patients who underwent L had longer post-operative hospitalization stay (mean 5.3 vs. 4.3 days; p < 0.001). The 5 year survival for patients with CT was 95% in the L versus 93% in the PL group (p = 0.62), and for ACT 89% in the L versus 81% PL group (p = 0.28). In a multivariate analysis increasing age was the only prognostic factor, and was associated with inferior survival. The HR for death comparing PL to L was 1.09 (95% CI: 0.65-1.78; p = 0.71) for CT and 1.25 (95% CI: 0.45-3.23; p = 0.65) for ACT. Conclusions: Patients with localized node-negative CT and ACT have excellent 5 year survival. Performing a lobectomy with mediastinal node dissection may not provide additional benefit compared to partial lobectomy, but this may increase the length of hospital stay.

8533 Background: BNET are a rare and frequently indolent group of neoplasms. Lobectomy is frequently done for patients with non-metastatic disease, and the role of adjuvant chemotherapy for patients with node positive disease (N+) is debated. Methods: Utilizing the National Cancer Database from 2004-2012 we identified 1682 patients with N+ non-metastatic BNET. All patients underwent primary resection, had pathologically confirmed diagnosis, complete follow up data, and were alive > 30 days following surgery. Overall survival (OS) was analyzed utilizing Kaplan-Meier curves, and log-rank tests were used to compare 2 groups of patients that differed based on receiving or not adjuvant chemotherapy. Subgroup analyses were performed based on histologic subtypes. Cox proportional hazards was performed to control for age, sex, race, grade, surgical margins, type of surgery, year of diagnosis, Charlson/Deyo Score, insurance, facility type, and location. Results: 651 patients with typical carcinoid (CT), 239 atypical carcinoid (ACT), 426 large cell neuroendocrine carcinoma (LCNEC), and 366 neuroendocrine carcinoma (NEC) were analyzed. The cohort median age was 61, and the female:male ratio was 1.8 for CT, ACT and NEC, and 1 for LCNEC 90% of patients were White and there were no significant differences amongst histologic subtypes. 6% of patients with CT received ADJ-CT, compared to 40% ACT, 42% NEC, and 70% LCNEC. In a multivariate analysis, only increasing age was associated with worse prognosis across all histologic subtypes, and non-academic facility for CT, and male sex for NEC. ADJ-CT was not associated with OS benefit for patients with ACT (HR 1.1; 95% CI 0.68-1.78; p:0.6), was associated with inferior OS in CT (HR: 3.8 (95% CI 1.9-7.0; p = 0.004) and NEC (HR: 2.15; 95% CI 1.5-3.0; p < 0.001), and may provide benefit for LCNEC (HR: 0.67; 95% CI 0.5-0.9; p = 0.009). Conclusions: Adjuvant chemotherapy was not associated with survival benefit for patients with node positive and non-metastatic BNET except for LCNEC, and may be harmful for patients with CT and NEC.