541P - Integrated analysis of randomized controlled trials IMpower130 and IMpower132 for advanced non-squamous non-small cell lung cancer (NSCLC)

Background

Platinum doublet (PtD) plus atezolizumab (ATZ) therapy is one of the standard therapies for advanced NSCLC. However, limited data have been reported for the elderly and patients (pts) with organ dysfunction. Especially, the data for the population aged ≥ 75 years, as defined by the Japan Lung Cancer Society guidelines for NSCLC, and renal dysfunction are insufficient and required. We focused on these points and conducted a post hoc analysis of efficacy and safety using data from two clinical trials.

Methods

The data from two randomized phase 3 clinical trials of PtD plus ATZ, IMpower130 (IM130: carboplatin and nab-paclitaxel with ATZ) and IMpower132 (IM132: carboplatin or cisplatin and pemetrexed with ATZ) were utilized for the integrated analysis. The efficacy and safety were evaluated in pts who were judged to be eligible based on the research protocol and ethics review committee approval. Kaplan-Meier estimates and hazard ratios for PFS and OS were provided.

Results

The subgroup aged ≥ 75 years included 131 pts: 80 pts in the ATZ group (Group A) and 51 pts in the chemotherapy group (Group C) in the integrated population. The median PFS was 8.4 months and 7.1 months (HR=0.59, 95% CI 0.40–0.88), and the median OS was 28.2 months and 15.9 months (HR=0.65, 95% CI 0.39–1.07). The subgroups with Baseline Creatinine Clearance (CCr) of 45 ≤ CCr < 60 mL/min were 57 pts (Group A: 37 pts, Group C: 20 pts) for IM130 and 53 pts (Group A: 28 pts, Group C: 25 pts) for IM132. The PFS and OS for the subgroups were HR=0.46 (95% CI 0.25–0.86) and HR=0.66 (95% CI 0.32–1.37) in IM130 and were HR=0.60 (95% CI 0.32–1.13) and HR=1.12 (95% CI 0.52–2.43) in IM132. Grade ≥ 3 treatment-related adverse events (TRAEs; Groups A and C) were reported in 70.3% and 62.8% of pts ≥ 75 years in the integrated population. In the 45 ≤ CCr < 60 mL/min subgroup in each study, Grade ≥ 3 TRAEs were 78.0% and 42.9% in IM130, and 57.1% and 72.0% in IM132.

Conclusions

The post hoc analysis showed that the combination therapy of PtD and ATZ demonstrated favorable PFS and OS in pts aged ≥ 75 years in the integrated population with tolerable safety. In addition, the combination of carboplatin and nab-paclitaxel with ATZ in IM130 has shown favorable PFS and OS even in pts with renal dysfunction.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Chugai Pharmaceutical Co., Ltd.

Funding

Chugai Pharmaceutical Co., Ltd.

Disclosure

M. Nishio: Financial Interests, Personal, Speaker, Consultant, Advisor: Ono Pharmaceuticals, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, Lilly, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, Janssen. S. Watanabe: Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Lilly, Pfizer, Novartis Pharma, AstraZeneca, Chugai Pharma, Bristol-Myers, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Nippon Kayaku. H. Udagawa: Financial Interests, Institutional, Funding: Takeda, Boehringer Ingelheim. N. Aragane: Financial Interests, Institutional, Funding: Taiho Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb. H. Saito: Financial Interests, Institutional, Research Grant: Chugai Pharma, AstraZeneca, Ono Pharma, Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma, AstraZeneca, Ono Pharma, Bristol Myers Squibb, Boehringer Ingelheim, Pfizer. All other authors have declared no conflicts of interest.