Search

Background: Programmed cell-death 1 antibodies (PD-1 Ab) improve overall survival (OS) for patients with advanced melanoma in trials; however, safety data in patients ≥75 years are lacking. The prognostic significance of and risk factors for PD-1 Ab discontinuation due immune related adverse events (irAE) are also uncertain., Methods: Patients with advanced melanoma receiving frontline PD-1 Ab at British Columbia Cancer outside of clinical trials between 10/2015-10/2019 were retrospectively analyzed. The incidence and subtypes of irAE were compared between age subgroups <75 and ≥ 75 years. Univariable logistic regression identified variables associated with treatment discontinuation within four months of PD-1 Ab initiation. Cox proportional hazard regression models were used to determine factors significantly associated with OS., Results: 302 patients were identified, of whom 126 (41.7%) were ≥ 75 years. During all follow-up, 15.9% of patients experienced irAE grade 3/4 and 27.2% of the cohort stopped PD-1 Ab due to immune toxicity. irAE incidence, hospitalization, and need for steroids by the four-month landmark were similar amongst age groups. Advanced age was not associated with risk of PD-1 Ab discontinuation from irAE on logistic regression. For the entire cohort, pre-treatment factors associated with shorter OS on multivariable analysis were ECOG performance status ≥1, M1d stage, lactate dehydrogenase >224, and neutrophil/ lymphocyte ratio ≥ 5. On four-month landmark multivariable analysis, treatment discontinuation due to irAE was significantly associated with worse OS., Conclusion: Patients aged ≥75 years experienced similar irAE rates and treatment discontinuation for immune toxicity compared to younger patients. As PD-1 Ab discontinuation due to irAE was associated with shorter OS, efforts to treat irAE early are warranted to potentially avoid therapy cessation., Competing Interests: Declaration of Competing Interest Dr. Doran Ksienski has received honoraria for continuing medical education (CME) events from Bristol Myers Squibb, SunPharma, and Merck and an educational grant from AstraZeneca. Dr. Angela Chan has collected honoraria for CME events from Bristol Myers Squibb, Merck, AstraZeneca, Novartis, SunPharma, Pfizer, and Roche. Dr. Pauline Truong receives writing and royalty fees from UpToDate, Wolster Kluwer Health Publishing. For the remaining authors none were declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: Induction ipilimumab and nivolumab followed by maintenance nivolumab improve overall survival compared with ipilimumab alone in patients with advanced melanoma, but immune-related adverse events (irAE) occur commonly. The need for induction discontinuation because of irAE and the relationship between irAE and survival in non-trials patients are unclear., Materials and Methods: Patients with unresectable stage III-IV melanoma receiving first-line combination immunotherapy at one of six centres between December 2017 and February 2020 outside of trials were identified retrospectively. Landmark 12-week Kaplan-Meier analyses and log-rank tests were used to evaluate associations between discontinuation of induction therapy on overall survival and time to treatment failure (TTF). Multivariable analysis of factors influencing overall survival and TTF was undertaken., Results: Among 95 patients, the median age was 62 years, 38.9% had Eastern Cooperative Oncology Group performance status ≥1 and 22.1% had brain metastases. The median follow-up for the whole cohort was 19.8 months by the reverse Kaplan-Meier method. Any grade and grade 3-4 irAE were noted in 78.9% and 44.2% of the cohort, respectively. 44.2% of patients completed induction immunotherapy, whereas 41.1% did not due to irAE. Twelve-week landmark overall survival and TTF were similar in patients who completed induction versus those who did not due to irAE. On multivariable analysis, any grade irAE (versus none) was associated with longer overall survival (hazard ratio = 0.35, 95% confidence interval 0.15-0.82, P = 0.02) and TTF (hazard ratio = 0.38, 95% confidence interval = 0.17-0.81, P = 0.01). Grade 3-4 irAE correlated with longer TTF (hazard ratio = 0.45, 95% confidence interval = 0.20-1.01, P = 0.05)., Conclusion: In this population-based cohort, discontinuation of induction immunotherapy as a result of irAE did not adversely affect overall survival or TTF. irAE observed during ipilimumab and nivolumab induction were associated with improved survival outcomes., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objectives: To explore the association of age with development of immune related adverse events (irAE) and survival in patients with advanced nonsmall cell lung cancer (aNSCLC) receiving programmed cell death 1 antibodies (PD-1 Ab) outside of clinical trials., Methods: A multicenter retrospective study of PD-1 Ab prescription for patients with aNSCLC between 06/2015-11/2018 at BC Cancer. Multivariable (MVA) logistic regression identified baseline variables associated with irAE manifested within 3 months of PD-1 Ab initiation. Overall survival (OS) analyzed in a propensity-score matched cohort and survival outcomes compared between age groups by stratified log-rank. Six-week landmark analysis was performed and OS compared between patients with interrupted versus continuous treatment by log-rank., Results: Of 527 patients, 40.6% were age ≤ 64 years, 40.6% were 65-74 years, and 18.8% were ≥ 75 years. In MVA, ECOG performance status 2/3 (p = .034), squamous histology (p = .031), and nivolumab therapy (vs. pembrolizumab, p = .012) were associated with increased odds of irAE by 3 months of treatment. Across age groups no difference existed in any grade irAE (p = .98), hospitalization (p = 1.0), or corticosteroids use (p = .51). The propensity score-matched survival analysis comprised 77 patients from each age group; all covariates were balanced. OS did not differ significantly by age in the matched cohort (p = .17). Treatment interruption due to irAE at 6 weeks was more common in patient ≥75 years (vs. <75, p = .055) and correlated with lower OS (p = .002)., Conclusion: In this cohort of patients with aNSCLC treated in routine clinical practice with PD-1 Ab, immune-toxicity and observed survival were similar amongst age groups., Competing Interests: Declaration of Competing Interest Dr. Doran Ksienski- honoraria for continuing medical education events from Merck Canada and Bristol Myers Squibb Canada. Unrestricted education grant received from AstraZeneca Canada. Dr. Zia Poonja- honoraria for continuing medical education events from Merck Canada, Bristol Myers Squibb Canada, and AstraZeneca Canada. Dr. Angela Chan- Honoria for continuing medical education events from Merck Canada, Bristol Myers Squibb Canada, AstraZeneca Canada, Genomic Health, Sanofi-Aventis Canada, EMD Serono, Genomic Health, Novartis, Pfizer, Roche, Takeda., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Although PD-1 antibodies (PD1 Ab) are the standard of care for advanced non-small-cell lung cancer (ansclc), most patients will progress. We compared survival outcomes for patients with ansclc who received systemic therapy (st) after progression and for those who did not. Additionally, clinical characteristics that predicted receipt of st after PD1 Ab failure were evaluated., Methods: All patients with ansclc in British Columbia initiated on nivolumab or pembrolizumab between June 2015 and November 2017, with subsequent progression, were identified. Eligibility criteria for additional st included an Eastern Cooperative Oncology Group (ecog) performance status (ps) of 3 or less and survival for more than 30 days from the last PD1 Ab treatment. Post-progression survival (pps) was assessed by landmark analysis. Baseline characteristics associated with pps were identified by multivariable analysis., Results: Of 94 patients meeting the eligibility criteria, 33 received st after progression. In 75.6%, a PD1 Ab was received as first- or second-line treatment. The most common sts were erlotinib (36.4%) and docetaxel (27.3%). No statistically significant difference in median pps was observed between patients who did and did not receive st within 30 days of their last PD1 Ab treatment (6.9 months vs. 3.6 months, log-rank p = 0.15.) In multivariable analysis, factors associated with increased pps included an ecog ps of 0 or 1 compared with 2 or 3 [hazard ratio (hr): 0.42; 95% confidence interval (ci): 0.24 to 0.73; p = 0.002] and any response compared with no response to PD1 Ab (hr: 0.54; 95% ci: 0.33 to 0.90; p = 0.02)., Conclusions: In this cohort, only 35.1% of patients eligible for post-PD1 Ab therapy received st. Post-progression survival was not significantly affected by receipt of post-progression therapy. Prospective trials are needed to clarify the benefit of post-PD1 Ab treatments., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none., (2020 Multimed Inc.)

Introduction: The programmed death 1 antibodies (PD-1 Ab) nivolumab and pembrolizumab improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). We evaluated the correlation between immune-related adverse events (irAE) and treatment interruption due to irAE on clinical efficacy of PD-1 Ab in advanced NSCLC., Patients and Methods: Advanced NSCLC patients treated with PD-1 Ab between June 2015 to November 2017 at BC Cancer were identified. Demographic, tumor, treatment details, and frequency and grade (Common Terminology Criteria for Adverse Events, version 4.0) of irAE were abstracted from chart review. Kaplan-Meier curves of OS from initiation of PD-1 Ab were generated. Multivariable analysis with 6- and 12-week landmark analysis was performed by Cox proportional hazard regression models., Results: In a cohort of 271 patients, irAEs were observed in 116 patients (42.8%). Nivolumab recipients developing colitis had lower OS compared to those who did not at the 6-week landmark (P = .010) and 12-week landmark (P = .072). For the entire cohort, 56 patients (20.7%) needed treatment interruption because of an irAE. Treatment interruption correlated with lower OS at the 6-week landmark (P = .005) and 12-week landmark (P = .008). Six-week landmark multivariable analysis identified Charlson Comorbidity Index score of 3 or higher, Eastern Cooperative Oncology Group Performance Status of 2 or higher, presence of liver metastases, and irAE greater than grade 2 versus no irAE to be associated with decreased OS (each P < .05)., Conclusion: Treatment interruption due to irAE was associated with a lower median OS compared to continuous PD-1 Ab therapy. Shorter OS seen with severe irAE might reflect the need for improved physician education in irAE treatment algorithms., (Copyright © 2018 Elsevier Inc. All rights reserved.)