As reported in the Journal of Clinical Oncology by Joel Neal, MD, PhD, and colleagues, the phase III CONTACT-01 trial has shown no significant improvement in overall survival with atezolizumab plus cabozantinib vs docetaxel after checkpoint inhibitor treatment and chemotherapy in patients with metastatic non–small cell lung cancer (NSCLC).

Joel Neal, MD, PhD

Study Details

The open-label trial included 366 patients with metastatic NSCLC and disease progression after concurrent or sequential anti–PD-L1/PD-1 treatment and platinum-containing chemotherapy. They were enrolled from sites in 15 countries between October 2020 and November 2021. Patients were randomly assigned to receive 21-day cycles of atezolizumab at 1,200 mg on day 1 and cabozantinib at 40 mg once daily (n = 186) or docetaxel at 75 mg/m² on day 1 (n = 180).  Treatment was continued until disease progression or unacceptable toxicity (or to loss of clinical benefit with atezolizumab/cabozantinib). The primary endpoint of the trial was overall survival.

Overall Survival

At clinical cutoff in September 2022, minimum follow-up was 10.9 months. Median overall survival was 10.7 months (95% confidence interval [CI] = 8.8–12.3 months) in the atezolizumab/cabozantinib group and 10.5 months (95% CI = 8.6–13.0 months) in the docetaxel group (hazard ratio [HR] = 0.88, 95% CI = 0.68–1.16, P = .367). Rates at 1 year were 43.3% (95% CI = 36.0%–50.6%) vs 44.1% (95% CI = 36.2%–52.1%). Among patients with available PD-L1 status, median overall survival was 9.5 months vs 9.2 months among 68 vs 70 patients with PD-L1 < 1% (HR = 0.92, 95% CI = 0.61–1.41) and 11.6 months vs 11.1 months among 100 vs 103 patients with PD-L1 ≥ 1% (HR = 0.90, 95% CI = 0.62–1.29).

Median progression-free survival was 4.6 months (95% CI = 4.1–5.6 months) in the atezolizumab/cabozantinib group vs 4.0 months (95% CI = 3.1–4.4 moths) in the docetaxel group (HR = 0.74, 95% CI = 0.59–0.92). Rates at 6 and 12 months were 39.5% vs 23.7% and 14.7% vs 8.4%, respectively. Subsequent anticancer therapy was received by 34.4% of patients in the atezolizumab group, most commonly chemotherapy (31.2%), and by 37.8% of patients in the docetaxel group, most commonly chemotherapy (30.6%).

Adverse Events

The most common treatment-related adverse events of any grade were diarrhea (40.5%), decreased appetite (24.9%), and palmar-plantar erythrodysesthesia syndrome (21.6%) in the atezolizumab/cabozantinib group, and alopecia (22.2%) and asthenia (21.6%) in the docetaxel group. Grade 3 or 4 treatment-related adverse events occurred in 39.5% vs 34.7% of patients. Serious adverse events occurred in 38.4% of the atezolizumab/cabozantinib group, most commonly pneumonia (5.4%), and in 34.7% of the docetaxel group, most commonly pneumonia (6.0%) and febrile neutropenia (4.8%). Adverse events led to discontinuation of treatment in 17.3% vs 14.4% of patients. Treatment-related adverse events led to death in four patients (2.2%) in the atezolizumab/cabozantinib group (due to pneumonitis in two and pulmonary hemorrhage and pneumopericardium in one each) and in one patient in the docetaxel group (due to sepsis). The investigators concluded, “Atezolizumab plus cabozantinib after disease progression following anti–PD-L1/PD-1 immunotherapy and platinum-containing chemotherapy for metastatic NSCLC did not improve overall survival compared with docetaxel. Safety was consistent with known profiles of these agents.”

Dr. Neal, of the Stanford Cancer Institute, Stanford University, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by F. Hoffmann-La Roche Ltd. For full disclosures of the study authors, visit ascopubs.org.