IMpower150 shows positive benefit-risk profile with ABCP in nonsquamous NSCLC

The four-drug atezolizumab, bevacizumab, carboplatin and paclitaxel (ABCP) regimen is tolerable and manageable compared with the three-drug atezolizumab, carboplatin and paclitaxel (ACP) regimen and bevacizumab, carboplatin and paclitaxel (BCP) regimen for first-line treatment of nonsquamous non-small-cell lung cancer (NSCLC), according to safety and patient-reported outcome (PRO) data of the IMpower150 trial.

“Results of this analysis informs on the tolerability of atezolizumab administered in combination with bevacizumab and chemotherapy as first-line treatment in nonsquamous NSCLC,” said the researchers. [J Clin Oncol 2020;38:2530-2542]

Among the safety-evaluable intention-to-treat (ITT) population (n=1,187) of the phase III trial, 400, 393 and 394 patients with metastatic nonsquamous NSCLC were randomized to receive ACP, ABCP or BCP every 3 weeks for 4–6 cycles (ie, induction phase). This was followed by maintenance therapy with atezolizumab, bevacizumab, or both, given to 305, 270 and 312 patients in the ACP, ABCP and BCP arms, respectively.

The treatment duration for atezolizumab, bevacizumab, carboplatin and paclitaxel was 6.4–8.3 months, 5.1–6.7 months, 2.1–2.2 months and 2.1–2.2 months, respectively, while the median duration of follow-up in the ACP, ABCP and BCP groups was 19.6 months, 19.6 months and 19.7 months, respectively.

Safety analyses showed higher rates of adverse events (AEs) during the induction vs maintenance phase across all treatment groups (ACP, 95.5 percent vs 85.2 percent) (ABCP, 96.7 percent vs 92.6 percent) (BCP, 98.7 percent vs 81.1 percent).

Grade 1/2 AEs accounted for the majority of the most common AEs (ie, ≥20 percent overall incidence) reported across all treatment arms. Alopecia (46.8 percent) and nausea (33.3 percent) in the ABCP arm, and alopecia (44.0 percent) and anaemia (33.5 percent) in the ACP arm were the most common AEs during the induction phase. In the maintenance phase, hypertension was the most commonly reported AE, occurring in 18.9 percent vs 12.2 percent vs 0.7 percent of patients in the ABCP vs BCP vs ACP arm.

Similarly, the incidence of serious AEs (SAEs) was higher during the induction vs maintenance phase across all treatment arms (ACP, 28.3 percent vs 20.0 percent) (ABCP, 28.5 percent vs 26.3 percent) (BCP, 26.4 percent vs 13.0 percent).

The overall incidence of AEs leading to discontinuation of any study treatment was 13.3 percent, 33.8 percent and 24.9 percent in ACP arm, ABCP arm and BCP arm, respectively. Pneumonitis was the most common SAE that led to atezolizumab discontinuation (≥1 percent of patients) in both the induction and maintenance phases in the ACP and ABCP arms.

Rash, hypothyroidism and hepatitis laboratory abnormalities were the most common immune-related adverse events (irAEs) (ie, ≥1 percent overall incidence) reported across all treatment arms. ACP- and ABCP-associated irAEs developed within the first 3–4 months of treatment, persisted for approximately 2 months, and were managed by corticosteroids.

PRO questionnaires, namely European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 and EORTIC-Lung Cancer 13 (EORTIC QLQ-LC13), were completed by >88 percent of patients at baseline and ≥70 percent of patients through cycle 18 of treatment across all arms.

Patient-reported disease burden was comparable in all arms at baseline, with a trend of improvement in physical functioning observed during the maintenance phase.

Patients in all treatment arms reported no clinically meaningful worsening in mean health-related quality of life (HRQoL), physical functioning, or symptom severity (apart from peripheral neuropathy). A trend of improvement of lung cancer-related symptoms from baseline through cycle 13.