Current recommendations for first-line therapy for patients with metastatic non–small cell lung cancer (NSCLC) includes checkpoint inhibitor monotherapy, dual checkpoint inhibition, or in combination with chemotherapy. In a recently published study, researchers compared outcomes with combination chemo-immunotherapy versus dual checkpoint inhibition as first-line treatment for patients with metastatic NSCLC.
According to a study published in the Journal of Thoracic Oncology, adding chemotherapy to first-line durvalumab plus tremelimumab did not enhance overall survival (OS) in patients with stage IV NSCLC. The researchers conducted an open-label, randomized clinical trial that enrolled 301 patients at 44 sites in Canada and Australia. Patients with treatment-naive, metastatic NSCLC without sensitizing epidermal growth factor receptor (EGFR) or anaplastic large-cell lymphoma kinase (ALK) alterations were randomized (1:1) to receive treatment with durvalumab plus tremelimumab with or without platinum doublet chemotherapy.
The primary endpoint was OS. Secondary endpoints were progression-free survival (PFS), overall response rate (ORR), and safety. The patients had a median age of 64 years (range, 27 to 87 years), 53.8% were men, 70.4% had stage IVB disease, and 81.7% had nonsquamous NSCLC.
Patients were randomly assigned to treatment with durvalumab, tremelimumab, and chemotherapy (151 patients), or durvalumab-tremelimumab only (150 patients). Baseline characteristics were usually well balanced between the arms. The average duration of treatment was 7.4 months in the chemotherapy arm and 3.3 months in the durvalumab-tremelimumab arm, and the median follow-up was 16.6 months.
The ORR was significantly greater in the chemotherapy arm than in the durvalumab-tremelimumab arm—42.4% and 29.3%, respectively (odds ratio, 1.69; 95% CI, 1.04-2.76). However, the median duration of partial response was comparable between the arms—8.2 months and 7.7 months, respectively. The results indicated that the average PFS was significantly longer in the chemotherapy arm than in the durvalumab-tremelimumab arm—7.7 months and 3.2 months, respectively (hazard ratio [HR], 0.67, 95% CI, 0.52-0.88; P = .003).
The researchers also indicated that there was no significant difference in OS between the arms. The average OS was 16.6 months in the chemotherapy arm and 14.1 months in the durvalumab-tremelimumab arm (HR, 0.88; 90% CI, 0.67-1.16; P = .46). The 1-year OS rate was 59% and 55%, respectively. The rate of grade 3 or higher adverse events (AEs) was reported as 82% in the chemotherapy arm, 70% in the durvalumab-tremelimumab arm, and the rate of treatment discontinuation due to AEs was 23% and 14%, respectively. The researchers indicated that there were five treatment-related deaths in the chemotherapy arm and three in the durvalumab-tremelimumab arm
The authors concluded that the addition of chemotherapy to durvalumab plus tremelimumab in the first-line treatment of stage IV NSCLC did not improve survival compared with durvalumab plus tremelimumab alone. They also noted that further study is necessary to identify patients that benefit from initial immunotherapy alone versus combination chemotherapy plus immunotherapy as first-line treatment.
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