Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non–Small-Cell Lung Cancer

Abstract

PURPOSE Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non–small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC. METHODS Patients were randomly assigned to receive atezolizumab, carboplatin, and paclitaxel (ACP), ABCP, or BCP. Coprimary end points were overall survival and investigator-assessed progression-free survival. The incidence, nature, and severity of adverse events (AEs) were assessed. PROs, a secondary end point, were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 and EORTC QLQ-Lung Cancer 13. RESULTS Overall, 400 (ACP), 393 (ABCP), and 394 (BCP) patients were safety evaluable (ie, intention-to-treat population that received one or more doses of any study treatment). More patients had grade 3/4 treatment-related AEs during the induction versus maintenance phase (ACP, 40.5% v 8.2%; ABCP, 48.6% v 21.2%; BCP, 44.7% v 11.1%). During induction, the incidence of serious AEs (SAEs) was 28.3%, 28.5%, and 26.4% in the ACP, ABCP, and BCP arms, respectively. During maintenance, SAE incidences were 20.0%, 26.3%, and 13.0%, respectively. Completion rates of the PRO questionnaires were > 88% at baseline and remained ≥ 70% throughout most study visits. Across arms, patients on average reported no clinically meaningful worsening of global health status or physical functioning scores through cycle 13. Patients across arms rated common symptoms with chemotherapy and immunotherapy similarly. CONCLUSION ABCP seems tolerable and manageable versus ACP and BCP in first-line nonsquamous NSCLC. Treatment tolerability differed between induction and maintenance phases across treatment arms. PROs reflect a minimal treatment burden (eg, health-related quality of life, symptoms) with each regimen.

Assessment of the Clinical Trials Safety Profile of PD-1/PD-L1 Inhibitors Among Patients With Cancer: An Updated Systematic Review and Meta-Analysis

“…Fifty-three articles were deemed to meet our preliminary selection criteria , of which 44 articles were selected for the final comprehensive analysis (18-21, 23-30, 32-42, 44-50, 52, 53, 56, 57, 61-70). The results of 6 clinical trials had been reported in multiple platforms: CheckMate 067 (n = 4) (57-60), PACIFIC (n = 3) (54-56), CheckMate 227 (n = 2) (21,22), OAK (n = 2) (31, 32), KeyNote 054 (n = 2) (51,52) and IMpower 150 (n = 2) (42,43). When such duplications were noted, only one was selected for the meta-analysis.…”

“…The clinical trials were further stratified into seven groups according to the treatment regimen as shown in Table 1. The classes are Group A (PD-1/PD-L1 vs Chemotherapy) , Group B (PD-1/PD-L1 + Chemotherapy vs Chemotherapy) (19,(41)(42)(43)(44)(45)(46)(47)(48)(49), Group C (PD-1/PD-L1 vs Placebo) (50-56), Group D (PD-1 vs PD-1+CTLA-4) (21,22,50,(57)(58)(59)(60)(61), Group E (PD-1+CTLA-4 vs CTLA-4) (57-60, 62), Group F (PD-1 vs CTLA-4) (57)(58)(59)(60)63), and Group G (PD-1/PD-L1 vs PD-1/PD-L1 + Chemotherapy) (19,26). The risks for the various types of adverse events within each group were then evaluated.…”

Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer

“…Therapies that block immune checkpoints show longer-lasting responses than traditional chemotherapy and have been approved by the FDA for the treatment of multiple cancer types, such as melanoma, nonsquamous cell carcinoma, OC, etc. (32)(33)(34). However, therapies that block immune checkpoints have low response rates in approximately 10%-30% cancers, which may be related to tumor mutational burden, PD-L1 expression level, IFN signaling and MHC-I loss.…”

First line Immunotherapy for Non-Small Cell Lung Cancer

“…IMpower150 randomized patients with nonsquamous NSCLC to treatment with chemotherapy plus Bevacizumab, chemotherapy plus atezolizumab or chemotherapy plus Bevacizumab and atezolizumab [55,109,110]. The chemotherapy used was Carboplatin, and Paclitaxel.…”

“…No improvement in OS was observed for patients with liver metastasis treated with chemotherapy and atezolizumab compared to patients treated with chemotherapy and Bevacizumab [109]. Recent report about safety and patient-reported outcomes of atezolizumab plus chemotherapy and Bevacizumab shows that this drug combination seems tolerable and with manageable toxicities [110]. For patients with nonsquamous NSCLC, with baseline liver metastases, the combination of chemotherapy, Atezolizumab and Bevacizumab could be an important option to consider in the first line.…”