Atezolizumab Plus Cabozantinib Failed to Improve Survival Among Previously Treated Patients With Metastatic Non-Small Cell Lung Cancer

Final Overall Survival Results From the Phase 3 CONTACT-01 Trial 

Results from the phase 3 CONTACT-01 trial demonstrated that atezolizumab plus cabozantinib did not improve overall survival (OS) or progression-free survival (PFS) compared to docetaxel among patients with metastatic non-small cell lung cancer (NSCLC) who experienced disease progression after treatment with anti-PD-L1/PD-1 immunotherapy and platinum-containing chemotherapy.

“Although checkpoint inhibitors have improved first-line treatment for NSCLC, a therapeutic need remains for patients whose disease does not respond or who experience disease progression after anti–PD-L1/PD-1 immunotherapy,” stated Joel Neal, MD, PhD, Stanford Cancer Institute, Stanford, California, and coauthors.

This multicenter, open-label study enrolled 366 patients with metastatic NSCLC who experienced disease progression after treatment with anti-PD-L1/PD-1 immunotherapy and platinum-containing chemotherapy. Patients were randomized on a 1-to-1 basis to receive either 1200 mg of atezolizumab once every 3 weeks plus 40 mg of cabozantinib once daily (n = 186) or 75 mg/m² of docetaxel once every 3 weeks (n = 180) in 21-day cycles. The primary end point was OS. Secondary end points included PFS and safety. 

At a follow up of 10.9 months, median OS was 10.7 months in the atezolizumab plus cabozantinib arm and 10.5 months in the docetaxel arm (stratified hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.68 to 1.16; P = .3668). Median PFS was 4.6 months in the atezolizumab plus cabozantinib arm and 4 months in the docetaxel arm. Grade ≥3 treatment-related adverse events occurred in 39.5% of patients in the atezolizumab plus cabozantinib arm and 34.7% of patients in the docetaxel arm. Serious adverse events occurred in 38.4% of patients in the atezolizumab plus cabozantinib arm and 34.7% of patients in the docetaxel arm. Grade 5 adverse events occurred in 7.6% and 6% of patients, respectively. 

“This study did not demonstrate activity of a multi-targeted tyrosine kinase inhibitor in combination with immune [checkpoint inhibitor] in unselected patients with progressive disease after immunotherapy,” noted Journal of Clinical Oncology associate editor Thomas E. Stinchombe, MD, Duke Cancer Institute, Durham, North Carolina. 

As Dr Neal et al concluded, “Overall, results do not support the combined use of atezolizumab plus cabozantinib after progression on previous checkpoint inhibitor and platinum-based chemotherapy in metastatic NSCLC.”

Source: 

Neal J, Pavlakis N, Kim SW, et al. CONTACT-01: A randomized phase III trial of atezolizumab + cabozantinib versus docetaxel for metastatic non-small cell lung cancer after a checkpoint inhibitor and chemotherapy. J Clin Oncol. Published online: March 29, 2024. doi:10.1200/JCO.23.02166