Pembrolizumab with or without chemotherapy among older adults with advanced lung adenocarcinoma: a national, nonrandomized open-label phase 2 trial (Alliance A171901)

BACKGROUND: Older adults remain underrepresented in prospective trials of immunotherapy for advanced lung cancer. To estimate pembrolizumab adverse events (AE), we conducted a multicenter, nonrandomized open-label phase II trial of oncologist-choice first-line pembrolizumab ± chemotherapy for older adults with advanced lung adenocarcinoma. METHODS: Alliance A171901 enrolled patients aged ≥70 years with stage IV or recurrent lung adenocarcinoma starting oncologist-choice of first-line pembrolizumab ± carboplatin and pemetrexed. The primary endpoint was the proportion of patients experiencing a solicited grade ≥3 AE within six months. Secondary endpoints included overall survival (OS), quality of life (QOL), and association of a geriatric assessment toxicity risk score with severe AEs. RESULTS: Among 95 evaluable patients, 43 (45.2%) received pembrolizumab and 52 (54.7%) received pembrolizumab plus chemotherapy. Median age was 77 years; 11.6% had an Eastern Cooperative Oncology Group performance status ≥2. During six months of treatment, 25.6% (95% CI 13.5 to 41.2%) experienced a solicited grade ≥3 AE in the monotherapy group and 42.3% (95% CI 28.7 to 56.8%) in the combination group. Median OS was 16.4 months (95% CI 10.1-not estimable) with monotherapy and 29.9 months (95% CI 16.4-not estimable) with combination therapy. QOL worsened during treatment. The geriatric assessment toxicity risk score was not associated with severe AEs with pembrolizumab ± chemotherapy. CONCLUSIONS: Older adults with advanced lung adenocarcinoma receiving pembrolizumab ± chemotherapy had comparable AE rates to those in prior registration trials that excluded frail patients. These findings can inform shared decision making and support inclusion of older adults in future trials. CLINICAL TRIAL: NCT04533451.