As reported in the Journal of Clinical Oncology by Tony Mok, MD, FRCPC, FASCO, and colleagues, final results of the primarily Asian phase III CheckMate 722 trial showed no progression-free survival benefit with the addition of nivolumab to chemotherapy in patients with EGFR-mutant metastatic non–small cell lung cancer (NSCLC) after disease progression on EGFR tyrosine kinase inhibitors.

Tony Mok, MD, FRCPC, FASCO

Study Details

In the open-label trial, 294 patients from sites in nine countries were randomly assigned between March 2017 and June 2020 to receive nivolumab (360 mg) plus platinum-doublet chemotherapy consisting of pemetrexed (500 mg/m²) plus cisplatin (75 mg/m²) or carboplatin (area under the curve = 5 or 6) once every 3 weeks for four cycles (n = 144) or platinum-doublet chemotherapy once every 3 weeks for four cycles (n = 150). Among patients without disease progression after four cycles, those in the nivolumab/chemotherapy group continued to receive nivolumab and pemetrexed every 3 weeks until disease progression, unacceptable toxicity, or for up to 2 years; those in the chemotherapy group received maintenance pemetrexed every 3 weeks until disease progression or unacceptable toxicity. Patients had to have disease progression after first- or second-generation EGFR tyrosine kinase inhibitor therapy (without EGFR T790M mutation) or osimertinib (with or without T790M mutation). Overall, 94.4% of patients in the nivolumab group and 92.7% in the control group were Asian. The primary endpoint was progression-free survival.

Progression-Free Survival

At final analysis, with a median follow-up of 38.1 months, median progression-free survival was 5.6 months (95% confidence interval [CI] = 4.5–6.8 months) in the nivolumab group vs 5.4 months (95% CI = 4.4–5.6 months) in the control group (hazard ratio [HR] = 0.75, 95% CI = 0.56–1.00, P = .0528); rates at 9 and 12 months were 25.9% vs 19.8% and 21.2% vs 15.9%, respectively.

Post hoc analyses of progression-free survival showed trends favoring nivolumab/chemotherapy in subgroups of patients with tumors harboring sensitizing EGFR mutations (HR = 0.72, 95% CI = 0.54–0.97), those who had received one line of previous EGFR tyrosine kinase inhibition (HR = 0.72, 95% CI = 0.54–0.97), and those with both criteria (HR = 0.64, 95% CI = 0.47–0.88).

Median overall survival was 19.4 months (95% CI = 16.1–21.0 months) in the nivolumab group vs 15.9 months (95% CI = 14.0–18.8 months) in the control group (HR = 0.82, 95% CI = 0.61–1.10), with 18-month rates of 54% vs 46%. Objective response rates were 31.3% vs 26.7%; median duration of response was 6.7 months vs 5.6 months.

Adverse Events

Grade 3 or 4 treatment-related adverse events occurred in 44.7% of patients in the nivolumab group vs 29.4% of the control group; the most common in both groups were anemia (15.6% vs 9.1%) and decreased neutrophils (11.3% vs 11.2%). Serious treatment-related adverse events occurred in 19.1% vs 9.1% of patents. Treatment-related adverse events led to discontinuation of treatment in 14.9% vs 7.7%. Treatment-related death occurred in two patients in each group, due to pneumonitis and interstitial lung disease in the nivolumab group and pneumonia and interstitial lung disease in the control group.

The investigators concluded, “Nivolumab plus chemotherapy did not significantly improve progression-free survival vs chemotherapy in patients with EGFR-mutated metastatic NSCLC previously treated with EGFR tyrosine kinase inhibitors. No new safety signals were identified.”

Dr. Mok, of the State Laboratory of Translational Oncology, The Chinese University of Hong Kong, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Bristol Myers Squibb in collaboration with ONO Pharmaceutical Company Ltd. For full disclosures of the study authors, visit ascopubs.org.