Roche's Atezolizumab Fails to Meet Primary PFS Endpoint in China Phase III Trial for First-Line Non-Squamous NSCLC

The abstract disclosed on the official website of the 2023 World Conference on Lung Cancer (WCLC) showed that Roche's Phase III clinical trial IMpower151 conducted in China did not meet the primary endpoint of PFS.

Previously, in the IMpower150 study, compared with bevacizumab combined with carboplatin and paclitaxel, atezolizumab (PD-L1) and bevacizumab (VEGF) combined with carboplatin and paclitaxel significantly improved PFS and OS in patients with metastatic non-squamous NSCLC (nsqNSCLC) without EGFR/ALK alterations. Based on this study, the FDA approved atezolizumab combined with bevacizumab and chemotherapy as a first-line treatment for metastatic nsqNSCLC in December 2018.

The IMpower151 study was conducted based on the IMpower150 study and carried out in China. It aims to evaluate the efficacy and safety of atezolizumab, bevacizumab, carboplatin + paclitaxel, or pemetrexed (ABCP) compared with BCP as first-line treatment for metastatic nsqNSCLC.

Patients with metastatic nsqNSCLC who have not received chemotherapy were randomly assigned 1:1 to receive Atezolizumab/placebo (1200mg) plus Bevacizumab (15mg/kg), Carboplatin (AUC 6), and Paclitaxel (175mg/m²) or Pemetrexed (500mg/m²) IV Q3W for 4 cycles, followed by maintenance therapy with Atezolizumab/placebo + Bevacizumab and Pemetrexed until unacceptable toxicity or lack of clinical benefit.

Stratification factors were EGFR/ALK genotype (mutant and wild-type, with a maximum of 50% wild-type) and PD-L1 expression (tumor cells SP263 <50% vs ≥50%). The primary endpoint was investigator (INV)-PFS (ITT population). Secondary endpoints included INV-PFS in the EGFR/ALK+ population, INV-PFS in the PD-L1 subgroup, independent review facility (IRF)-PFS, OS, ORR, and DOR.

As of February 2, 2023, the median follow-up time was 14 months. Of the 305 randomly assigned patients (ITT population), 297 (97.4%) used pemetrexed; 239 experienced PFS events.IMpower151 Did Not Meet the Primary Endpoint of INV-PFS in Metastatic nsqNSCLC，ABCP vs BCP: Median INV-PFS was 9.5 months vs 7.1 months(Stratified HR, 0.84; 95% CI: 0.65, 1.09; P=0.1838). INV-PFS was consistent with IRF-PFS.PFS in the EGFR/ALK+ subgroup was similar between the two groups., while a numerical difference was observed in the wild-type subgroup (10.4 months vs 7.0 months). No PD-L1-dependent PFS difference.

The biggest difference between the IMpower150 and IMpower151 studies is that 87% (1,045 patients) of the participants in the former did not have EGFR or ALK tumor mutations, while in the IMpower151 study, the proportion of EGFR/ALK wild-type participants did not exceed 50%. The author believes this should be the reason for the differing results of the two studies.

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