Background: Atezo (anti–PD-L1) + bev (anti-VEGF) + chemo prolonged PFS vs bev + chemo in patients (pts) with 1L nonsquamous mNSCLC in the randomized, Phase III IMpower150 study. PRO data, including symptom burden, functioning and health-related quality of life (HRQoL), were evaluated to assess overall clinical benefit in each treatment (Tx) arm. Methods: Pts received atezo 1200 mg + carboplatin (C) AUC 6 + paclitaxel (P) 200 mg/m² (Arm A) or atezo + bev 15 mg/kg + C + P (Arm B) vs bev + C + P (Arm C) IV q3w for 4 or 6 cycles per investigator decision, then maintenance atezo, atezo + bev, or bev, respectively. PRO data were collected using the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Prespecified analyses included the mean change from baseline in symptoms, functioning and HRQoL and time to deterioration (TTD) in lung cancer symptoms. Clinically meaningful change was defined as a ≥10-point change in score from baseline. Results: PRO completion rates were high (≥70% through cycle 23 for all arms). Mean changes from baseline indicated that a clinically meaningful worsening (≥10-point change) was not observed in any arm through cycle 13 (≈25% of pts remain in Arm C); HRQoL and physical functioning scores minimally decreased (Arm A: −2.83 and −3.39; Arm B: −1.8 and −3.98; Arm C: −1.92 and −2.6) with concurrent numerical worsening in Tx-related symptom scores (e.g., fatigue, constipation, nausea/vomiting). Following chemo completion, scores returned to baseline or numerically improved. HRQoL, physical functioning and Tx-related symptoms were comparable between Arms B and C. No difference was observed between arms in the TTD in lung cancer symptoms assessed. All arms reported numerical improvement in multiple lung cancer symptoms while on Tx. Conclusions: These data suggest that prolonged PFS in Arm B was achieved without compromising HRQoL or physical functioning despite higher Tx-related AEs than Arm C. PRO data reflected a minimal Tx burden across arms, further reduced following chemo discontinuation. Overall, PRO data support the positive benefit:risk of the clinical data with atezo + bev + chemo in 1L nonsquamous mNSCLC. Clinical trial information: NCT02366143