Search

Background The coronavirus disease 2019 (COVID‐19) pandemic has significantly impacted health care systems. However, to date, the trend of hospitalizations in the oncology patient population has not been studied, and the frequency of nosocomial spread to patients with cancer is not well understood. The objectives of this study were to evaluate the impact of COVID‐19 on inpatient oncology census and determine the nosocomial rate of COVID‐19 in patients with cancer admitted at a large academic center. Materials and Methods Medical records of patients with cancer diagnosed with COVID‐19 and admitted were reviewed to evaluate the temporal trends in inpatient oncology census during pre–COVID‐19 (January 2019 to February 2020), COVID‐19 (March to May 2020), and post–COVID‐19 surge (June to August 2020) in the region. In addition, nosocomial infection rates of SARS‐CoV‐2 were reviewed. Results Overall, the daily inpatient census was steady in 2019 (median, 103; range, 92–118) and until February 2020 (median, 112; range, 102–114). However, there was a major decline from March to May 2020 (median, 68; range, 57–104), with 45.4% lower admissions during April 2020. As the COVID‐19 surge eased, the daily inpatient census over time returned to the pre–COVID‐19 baseline (median, 103; range, 99–111). One patient (1/231, 0.004%) tested positive for SARS‐CoV‐2 13 days after hospitalization, and it is unclear if it was nosocomial or community spread. Conclusion In this study, inpatient oncology admissions decreased substantially during the COVID‐19 surge but over time returned to the pre–COVID‐19 baseline. With aggressive infection control measures, the rates of nosocomial transmission were exceedingly low and should provide reassurance to those seeking medical care, including inpatient admissions when medically necessary. Implications for Practice The COVID‐19 pandemic has had a major impact on the health care system, and cancer patients are a vulnerable population. This study observes a significant decline in the daily inpatient oncology census from March to May 2020 compared with the same time frame in the previous year and examines the potential reasons for this decline. In addition, nosocomial rates of COVID‐19 were investigated, and rates were found to be very low. These findings suggest that aggressive infection control measures can mitigate the nosocomial infection risk among cancer patients and the inpatient setting is a safe environment, providing reassurance., To understand the overall impact of COVID‐19 on health care delivery in the oncology setting, this study evaluated the inpatient oncology census, in comparison to historical data and infusion volume, at an institution with a high volume of COVID‐19 admissions.

Since its approval in April 2018, osimertinib has been widely adopted as first-line therapy for patients with advanced EGFR-mutant non -small cell lung cancer (NSCLC). Understanding osimertinib resistance mechanisms and currently available treatment options are essential to selecting optimal second line therapy for patients whose disease progresses during front-line osimertinib. Using data compiled from 6 osimertinib-resistance series, we describe here the heterogeneous profile of EGFR-dependent and independent mechanisms of osimertinib treatment failure. We identified MET alterations (7%-24%), EGFR C797X (0%-29%), SCLC transformation (2%-15%), and oncogene fusions (1%-10%) as the most common mechanisms of resistance. This review provides an evidence-based, algorithmic approach to the evaluation and management of post-osimertinib progression as well as a compendium of active, enrolling clinical trials for this population.

Introduction : Patients with EGFR-mutant lung cancer who have had disease progression on osimertinib commonly receive platinum doublet chemotherapy, but whether adding immunotherapy or bevacizumab provides additional benefit is unknown. Methods : This was a retrospective analysis at 2 university-affiliated institutions. Patients with EGFR-mutant lung cancer who had progression on osimertinib and received next-line therapy with platinum doublet chemotherapy (chemo), platinum doublet chemotherapy plus immunotherapy (chemo-IO), or platinum doublet chemotherapy plus bevacizumab (chemo-bev), were identified; patients who continued osimertinib with these regimens were included. Efficacy outcomes including duration on treatment (DOT) and overall survival (OS) from the start of chemotherapy were assessed. Associations of treatment regimen with outcomes were evaluated using adjusted Cox regression models, using pairwise comparisons between groups. Results : 104 patients were included: 57 received chemo, 12 received chemo-IO, and 35 received chemo-bev. In adjusted models, patients who received chemo-IO had worse OS than did those who received chemo (hazard ratio (HR) 2.66, 95% CI 1.25-5.65; p=0.011) or those who received chemo-bev (HR 2.37, 95% CI 1.09-5.65; p=0.030). A statistically significant difference in OS could not be detected in patients who received chemo-bev versus those who received chemo (HR 1.50, 95% CI 0.84-2.69; p=0.17). Conclusions : In this retrospective study, giving immunotherapy with platinum doublet chemotherapy after progression on osimertinib was associated with a worse OS compared with platinum doublet chemotherapy alone. Platinum doublet chemotherapy without immunotherapy (with consideration of continuation of osimertinib, in selected cases) is a reasonable choice in this setting, while we await results of clinical trials examining optimal next-line chemotherapy-based regimens in EGFR-mutant lung cancer. Micro Abstract : Optimal treatment of EGFR-mutated lung cancer after progression on osimertinib is unknown. We retrospectively evaluated outcomes in patients who received platinum doublet chemotherapy alone or in combination with immunotherapy or bevacizumab. We found that the addition of immunotherapy to chemotherapy was associated with worse survival; statistically significant differences in survival could not be detected with the addition of bevacizumab to chemotherapy.

Corresponding Author

Background Early reports suggested increased mortality from COVID‐19 in patients with cancer but lacked rigorous comparisons to patients without cancer. We investigated whether a current cancer diagnosis or cancer history is an independent risk factor for death in hospitalized patients with COVID‐19. Patients and Methods We identified patients with a history of cancer admitted to two large hospitals between March 13, 2020, and May 10, 2020, with laboratory‐confirmed COVID‐19 and matched them 1:2 to patients without a history of cancer. Results Men made up 56.2% of the population, with a median age of 69 years (range, 30–96). The median time since cancer diagnosis was 35.6 months (range, 0.39–435); 80% had a solid tumor, and 20% had a hematologic malignancy. Among patients with cancer, 27.8% died or entered hospice versus 25.6% among patients without cancer. In multivariable analyses, the odds of death/hospice were similar (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.65–1.82). The odds of intubation (OR, 0.46; 95% CI, 0.28–0.78), shock (OR, 0.54; 95% CI, 0.32–0.91), and intensive care unit admission (OR, 0.51; 95% CI, 0.32–0.81) were lower for patients with a history of cancer versus controls. Patients with active cancer or who had received cancer‐directed therapy in the past 6 months had similar odds of death/hospice compared with cancer survivors (univariable OR, 1.31; 95% CI, 0.66–2.60; multivariable OR, 1.47; 95% CI, 0.69–3.16). Conclusions Patients with a history of cancer hospitalized for COVID‐19 had similar mortality to matched hospitalized patients with COVID‐19 without cancer, and a lower risk of complications. In this population, patients with active cancer or recent cancer treatment had a similar risk for adverse outcomes compared with survivors of cancer. Implications for Practice This study investigated whether a current cancer diagnosis or cancer history is an independent risk factor for death or hospice admission in hospitalized patients with COVID‐19. Active cancer, systemic cancer therapy, and a cancer history are not independent risk factors for death from COVID‐19 among hospitalized patients, and hospitalized patients without cancer are more likely to have severe COVID‐19. These findings provide reassurance to survivors of cancer and patients with cancer as to their relative risk of severe COVID‐19, may encourage oncologists to provide standard anticancer therapy in patients at risk of COVID‐19, and guide triage in future waves of infection., This article focuses on whether a current cancer diagnosis or cancer history is an independent risk factor for death or hospice admission in hospitalized patients with COVID‐19.

Background For cancer patients, coronavirus disease 19 (COVID‐19) infection can lead to delays in cancer therapy both due to the infection itself and due to the need to minimize exposure to other patients and to staff. Clearance guidelines have been proposed, but expected time to clearance has not been established. Methods We identified all patients at a tertiary care hospital cancer center between 25 March 2020 and 6 June 2020 with a positive nasopharyngeal reverse transcriptase polymerase chain reaction (RT‐PCR) test for the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a cancer‐related visit within 3 years, and at least one follow‐up assay. We determined the time to clearance using American Society of Clinical Oncology (ASCO), the UK National Institute for Health and Care Excellence (UK‐NICE), and Centers for Disease Control and Prevention (CDC) criteria. A matched non‐cancer comparison cohort was also identified. Results Thirty‐two cancer patients were identified. Nineteen were cleared by ASCO criteria, with estimated median time to clearance of 50 days. Fourteen patients resumed chemotherapy prior to clearance. Using UK‐NICE criteria, median time to clearance would have been 31 days, and using CDC criteria, it would have been 13 days. The matched non‐cancer cohort had similar clearance time, but with less frequent testing. Conclusion SARS‐CoV‐2 clearance times differ substantially depending on the criteria used and may be prolonged in cancer patients. This could lead to a delay in cancer care, increased use of clearance testing, and extension of infection control precautions., In this single‐institution retrospective cohort study, the median time to SARS‐CoV‐2 clearance among cancer patients was 50 days using the ASCO/CDC criteria of two negative RT‐PCR assays >24 h apart. Using alternative criteria of one negative RT‐PCR assay (UK‐NICE) or CDC clinical criteria (10 days after first positive RT‐PCR and 3 days after last symptoms), median clearance times were 31 and 13 days, respectively.

Introduction Lung cancer is associated with severe coronavirus disease 2019 (COVID-19) infections. Symptom overlap between COVID-19 and lung cancer may complicate diagnostic evaluation. We aimed to investigate the incidence, symptoms, differential diagnosis, and outcomes of COVID-19 in patients with lung cancer. Methods To determine an at-risk population for COVID-19, we retrospectively identified patients with lung cancer receiving longitudinal care within a single institution in the 12 months (April 1, 2019 to March 31, 2020) immediately preceding the COVID-19 pandemic, including an “active therapy population” treated within the last 60 days of this period. Among patients subsequently referred for COVID-19 testing, we compared symptoms, laboratory values, radiographic findings, and outcomes of positive versus negative patients. Results Between April 1, 2019 and March 31, 2020, a total of 696 patients received longitudinal care, including 406 (58%) in the active therapy population. Among 55 patients referred for COVID-19 testing, 24 (44%) were positive for COVID-19, representing a cumulative incidence of 3.4% (longitudinal population) and 1.5% (active therapy population). Compared with patients who were COVID-19 negative, those who were COVID-19 positive were more likely to have a supplemental oxygen requirement (11% versus 54%, p = 0.005) and to have typical COVID-19 pneumonia imaging findings (5 versus 56%, p = 0.001). Otherwise, there were no marked differences in presenting symptoms. Among patients who were COVID-19 negative, alternative etiologies included treatment-related toxicity (26%), atypical pneumonia (22%), and disease progression (22%). A total of 16 patients positive for COVID-19 (67%) required hospitalization, and seven (29%) died from COVID-related complications. Conclusions COVID-19 was infrequent in this lung cancer population, but these patients experienced high rates of morbidity and mortality. Oncologists should maintain a low threshold for COVID-19 testing in patients with lung cancer presenting with acute symptoms.

ROS1-rearranged (also known as ROS1 fusion-positive) non-small-cell lung cancer is an uncommon but distinct molecular subgroup seen in approximately 1-2% of cases. Oncogene addiction due to constitutive ROS1 tyrosine kinase activation has allowed development of molecularly targeted therapies with remarkable anti-tumor activity. Both crizotinib and entrectinib, multitargeted tyrosine kinase inhibitors (TKIs) have now received approval by the FDA for treatment of patients with advanced ROS1-rearranged lung cancers; however, the clinical efficacy and safety of these drugs have been derived from expansion cohorts of single-arm phase I or basket clinical trials with relatively small populations of this clinically and molecularly distinct subgroup. Both drugs lead to high objective response rates (approximately 70-80%) and have manageable side effects, although only entrectinib has potent intracranial efficacy. Lorlatinib is an oral brain-penetrant ALK/ROS1 TKI with activity in both TKI-naive and some crizotinib-resistant settings (albeit with limited potency against the crizotinib/entrectinib-resistant ROS1-G2032R mutation). We describe cases of advanced ROS1-rearranged lung cancer receiving crizotinib, entrectinib, and/or lorlatinib in first and later line treatment settings to dissect the current state of evidence supporting management decisions for these patients. The next generation ROS1 TKIs (repotrectinib and DS-6051b), owing to their broad activity against kinase mutations including ROS1-G2032R in preclinical studies, hold promise to transform the current treatment paradigm and permit even further gains with regards to long-term outcomes in this subset of patients.

Purpose/Objective(s) Patients with stage III epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy (CRT) may not benefit from consolidation immune checkpoint inhibitors, and adjuvant EGFR tyrosine kinase inhibitor (TKI) treatment with osimertinib is now approved for stage IB-IIIA. Whether and how to integrate TKI into the treatment of unresectable or borderline resectable stage III disease is unclear. Materials/Methods Patients with stage III (AJCC 7th ed.) EGFR mutant NSCLC amenable to CRT ± surgery were enrolled onto an IRB-approved Phase II trial (clinicaltrials.gov registered) and received induction afatinib 40 mg QD x 2 months, either definitive or neoadjuvant CRT with cisplatin/pemetrexed, surgery if appropriate, and 2 years of adjuvant afatinib provided there was no primary progression during the induction phase. The trial was closed for slow accrual. The primary endpoint of objective response rate after induction TKI and early survival outcomes have been previously reported. This is a secondary analysis of recurrences and updated outcomes. Results Seventeen patients completed induction TKI and CRT ± surgery between 2012 and 2020. There were 74% females. Median age was 56 years (range, 34-75 years). Neoadjuvant and definitive median radiation doses were 54 Gy (range, 45-66 Gy) and 66.6 Gy (range, 63-72 Gy). Ten patients with biopsy confirmed N2 (n = 9) or N3 (n = 1) disease underwent surgery which showed a mediastinal sterilization rate of 60%. Adjuvant TKI was initiated in 14 patients including 1 case of off-protocol erlotinib. Three patients aborted TKI, 7 completed 2 years of TKI, 2 remained on TKI at last follow-up while 2 switched to other treatments after recurrence. Notably, of the 7 patients completing 2 years of TKI, 6 recurred after a median interval of only 3 months (range, 1-55 months) from the completion date. In total there were 11 recurrences. The dominant pattern of recurrence was distant with just 1 isolated local failure in a patient treated with definitive CRT. Five of 11 recurrences were CNS-only, all of which occurred after completion of adjuvant TKI at a median interval of 4 months. Four of these patients had intracranial disease control at last follow-up. No grade 3+ radiation treatment related toxic events were observed. With a median follow-up of 43.3 months for patients alive, median progression-free survival (PFS) and overall survival (OS) times were 32 months and not reached, respectively. 3-year PFS and OS rates were 31% (95% CI, 6-56%) and 69% (43-94%), respectively. Conclusion This trial highlights the efficacy of aggressive local therapy and the potential promise of TKI treatment for stage III EGFR mutant NSCLC though interpretations are limited by small sample size. One particular risk for patients was CNS-only recurrence suggesting that better CNS directed treatments and CNS surveillance strategies should be studied to increase cure rates in this unique, genotype-defined NSCLC population.

49 Background: COVID-19 in oncologic patients presents a clinical dilemma. To reduce the risk of adverse events as well as the risk of exposing others, many institutions have established protocols to define COVID-19 clearance. However, the optimal criteria for discontinuing infection precautions and/or resuming anticancer therapy in COVID-19 patients is unknown. Methods: We identified patients with a positive COVID-19 PCR at a tertiary care hospital between 3/25/2020 and 6/6/2020, and who also had seen an oncologist for a cancer-related diagnosis within the last 3 years. COVID-19 PCR testing was performed using the Abbott Laboratories m2000 platform in conjunction with either the Aldatu Biosciences PANDAA qDxTM SARS-CoV-2 or Abbott RealTime SARS-CoV-2 assays. At our institution, and per current ASCO guidelines, discontinuation of COVID-19 precautions requires two consecutive negative viral PCR tests > 24 hours apart. Results: During the follow-up period, we identified 32 patients with a positive COVID-19 PCR who were receiving active oncology care. Half of this cohort (16/32) had metastatic disease at the time of COVID-19 diagnosis. 17 patients were on active treatment at time of COVID-19 diagnosis (8 receiving cytotoxic chemotherapy). Among patients who met criteria for COVID-19 PCR clearance, median time to clearance was 37 days (range, 10-58 days). When accounting for censoring at the time of last COVID-19 assay, median time to clearance for all patients was estimated at 50 days. 14 patients resumed anti-cancer treatment prior to COVID-19 clearance (5 received cytotoxic chemotherapy), requiring substantial allocation of staff and resources for safe treatment isolated from other oncology patients. Among the 13 patients who met clearance criteria, 2 subsequently had a positive COVID-19 PCR after resumption of treatment. We explored COVID-19 clearance time under an alternative symptom/time based strategy based on CDC criteria (at least 10 days after first positive PCR and 3 days after last day of symptoms). Under this strategy, median time to COVID-19 clearance would be 14 days. Conclusions: In patients with cancer who develop COVID-19 infection, viral shedding can persist for many weeks after disease onset, but the implications of this shedding on likelihood of infection is unknown. Treatment of COVID-19 positive oncology patients requires substantial planning and resources. Test-based versus symptom/time-based strategies for determining discontinuation of precautions and resumption of treatment should be further investigated to provide safe and effective care.

9586 Background: High-dose osimertinib 160 mg QD (osi160) has activity in osi-naïve, EGFR+ NSCLC pts with CNS or leptomeningeal disease (LMD) per the BLOOM trial, but the role of dose-escalation for CNS progression (PD) and/or LMD that develops while on 80 mg QD (osi80) is unclear. We describe here our multi-institutional experience with osi160. Methods: 105 pts from 8 institutions with advanced EGFR+ NSCLC treated with osi160 were retrospectively reviewed. To assess the CNS efficacy of dose escalation for CNS PD, we focused on pts who escalated from osi80 to osi160 for CNS PD without the addition of chemo and/or RT during dose escalation (cohort A, 24 pts). We also examined osi escalation for CNS PD while receiving chemo and/or RT (cohort B, 34 pts) and those who started on osi160 for CNS PD as the initial osi dose without overlapping therapies (cohort C, 11 pts). Radiographic responses were clinically assessed via chart review of scan reports. Kaplan-Meier analysis was used for time-to-event endpoints. We defined median duration of CNS disease control (MedDurCNSCon) on osi160 as time from the start of osi160 to CNS PD or discontinuation of osi160. Results: Among the 105 pts, 69 (26M, 43F; median age 57) EGFR+ NSCLC pts (29 del19, 31 L858R, 9 other) received osi160 for CNS PD between 10/2013 and 1/2020. Median lines of therapy pre-osi was 1 (range 0-8). While all 69 pts had CNS PD at the start of osi160, 61 (90%) had isolated CNS/LMD PD, without systemic PD. In cohort A, osi160 monotherapy had a MedDurCNSCon of 3.8 mos (95% CI, 1.7 – 5.8). Cohort A pts with isolated LMD (11) had MedDurCNSCon 5.8 mos (95% CI, 1.7 – 9) while those with parenchymal mets only (11) had MedDurCNSCon of 2 mos (95% CI, 1 - 4.9). In cohort B, osi160 in combination with RT (22) and/or chemo (14), had a MedDurCNSCon of 5.1 mos (95% CI, 3.1 – 6.5). In cohort C, osi160 monotherapy had a MedDurCNSCon of 4.2 mos (95% CI, 1.6 – NA). Pts on osi160 had no severe or life-threatening side effects. Conclusions: In this real-world cohort of EGFR+ NSCLC pts with CNS and/or LMD PD on osi80, dose escalation to 160 provided modest benefit with median 3.8 mos added CNS disease control. Dose escalation appeared more effective in pts with LMD versus parenchymal disease (MedDurCNSCon of 5.8 vs 2 mos). Treatment intensification with osi escalation plus RT and/or chemo appeared to confer about 1 month additional CNS disease control (power for comparison limited). Osi naïve pts started at 160 for CNS PD derived similar benefit. While limited by small numbers and retrospective design, this study suggests we need improved strategies to optimally manage CNS PD arising on osi80.

9570 Background: Osimertinib (osi) is a 3rd generation EGFR tyrosine kinase inhibitor (TKI) approved for first line (1L) treatment of metastatic NSCLC harboring EGFR Exon 19 del and L858R (representing > 80% of EGFR activating mutations) or in NSCLC with EGFRT790M (the most common resistance mutation to 1st or 2nd generation TKI). However, it has not been well-studied in EGFR-mutant NSCLC harboring less common EGFR activating mutations such as G719X, L861Q, S768I, and exon 20 insertion (ins), among others. Methods: We conducted a multi-institution, retrospective study approved on institutional IRB protocols in a series of patients (pts.) with metastatic NSCLC treated with osi who harbored at least one atypical EGFR mutation, excluding those with concurrent L858R, Exon 19 del, or T790M. Kaplan-Meier analyses were generated with SPSS, v25 (IBM Corp., USA). Response was assessed by RECIST 1.1 in evaluable pts. Time on osi was employed as a surrogate endpoint for clinical benefit in this retrospective analysis. Results: Fifty-one NSCLC pts with uncommon EGFR mutations were identified among six US institutions. Pt characteristics: 72.5% women, median age 65 yo (44-83 yo), 82.3% ECOG PS 0-1, 43.1% never smoker, 100% lung adenocarcinoma, 58.8% Caucasian, 25.5% Asian, 3.9% Black, 2.0% Hispanic, and 9.8% Other. The most frequent mutations were L861Q (35.3%, N = 18), G719X (27.5%, N = 14), and Exon 20 ins (15.7%, N = 8). Osi was used in the 1L setting in 39.2% (N = 20). Median time on osi was 7.1 months (mo.) in the overall cohort (95% CI, 5.4 to 8.8 mo.) and 8.9 mo. (95% CI, 7.0 to 10.8 mo.) in pts receiving 1L osi. Patients harboring G719X (N = 4) and L861Q (N = 10) mutations had a median time on 1L osimertinib of 5.8 mo. and 19.3 mo., respectively. One patient’s tumor had an EGFR exon 19 ins and was on 1L osi with a partial response for 16.8 months. Two patients with Exon 20 ins were on 1L osi for 9.3 mo. and 8 mo., respectively. Conclusions: In this largest known clinically annotated dataset of patients with atypical EGFR-mutations treated with osi, activity was noted, though 1L clinical benefit on osi appears lower in this multicenter US cohort than in E19del or L858R. These results are comparable to the recently published prospective phase II trial ( Cho et al, 2019) conducted in Korea. Patients with L861Q and Exon 19 insertion appeared to benefit the most from osi in this time on treatment retrospective analysis. More detailed analysis of this cohort is planned and further prospective studies are warranted to determine clinical benefit of osi amongst diverse atypical EGFR-mutations.