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

Martin Reck, Thomas Wehler, Francisco Orlandi, Naoyuki Nogami, Carlo Barone, Denis Moro-Sibilot, Mikhail Shtivelband, Jose Luis González Larriba, Jeffrey Rothenstein, Martin Früh, Wei Yu, Yu Deng, Shelley Coleman, Geetha Shankar, Hina Patel, Claudia Kelsch, Anthony Lee, Elisabeth Piault, Mark A Socinski, Martin Reck, Thomas Wehler, Francisco Orlandi, Naoyuki Nogami, Carlo Barone, Denis Moro-Sibilot, Mikhail Shtivelband, Jose Luis González Larriba, Jeffrey Rothenstein, Martin Früh, Wei Yu, Yu Deng, Shelley Coleman, Geetha Shankar, Hina Patel, Claudia Kelsch, Anthony Lee, Elisabeth Piault, Mark A Socinski

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.

Trial registration: ClinicalTrials.gov NCT02366143.

Figures

FIG 1.
FIG 1.
Most common adverse events (AEs) overall and by phase of treatment. (A) Incidences of the most common (≥ 20% overall incidence) AEs reported in any treatment arm. Incidences of the most common AEs in the (B) induction and (C) maintenance phases. AEs that occurred during the induction phase had an onset on or after the first study drug treatment and up to 1 day before the date of the first dose of the maintenance therapy. AEs that occurred during the maintenance phase had an onset on or after the first dose of maintenance therapy. Overall AEs represent the sum of AEs with onset during the induction phase, the maintenance phase, and/or the AE reporting period. The AE reporting period includes those patients who discontinued induction therapy, never received maintenance therapy, and had an AE with onset > 30 days after the last dose of study treatment and during the AE reporting period as defined in the protocol. ABCP, atezolizumab plus bevacizumab, carboplatin, and paclitaxel; ACP, atezolizumab, carboplatin, and paclitaxel; BCP, bevacizumab, carboplatin, and paclitaxel.
FIG 2.
FIG 2.
Mean change in baseline score of patient-reported health-related quality of life (HRQOL) and physical functioning overall and by phase of treatment. (A) Mean change in baseline scores for global health status and physical functioning overall and during the (B) induction and (C) maintenance phases. Induction was defined as four or six 21-day cycles of atezolizumab plus bevacizumab, carboplatin, and paclitaxel (ABCP); atezolizumab, carboplatin, and paclitaxel (ACP); or bevacizumab, carboplatin, and paclitaxel (BCP). Maintenance started at cycle 4 or 6, with 21-day cycles of atezolizumab plus bevacizumab (in the ABCP arm), atezolizumab (in the ACP arm), or bevacizumab (in the BCP arm).
FIG 3.
FIG 3.
Mean change in baseline scores of patient-reported symptom severity. Mean change in baseline score through cycle 13 for (A) fatigue, (B) constipation, (C) diarrhea, (D) nausea/vomiting, (E) peripheral neuropathy, (F) sore mouth, (G) coughing, (H) chest pain, and (I) dyspnea. ABCP, atezolizumab plus bevacizumab, carboplatin, and paclitaxel; ACP, atezolizumab, carboplatin, and paclitaxel; BCP, bevacizumab, carboplatin, and paclitaxel.

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