When the press release for KEYNOTE-091 came out in mid-January, it was only logical to compare the outcomes for patients with those of the 2021 IMpower010 trial — both trials were looking at adjuvant immunotherapy following surgery for early-stage non–small cell lung cancer (NSCLC).
The KEYNOTE-091 trial announced an improvement in disease-free survival for patients with resected stage IB-IIIA NSCLC after receiving a year of adjuvant pembrolizumab.
The IMpower010 trial reported similarly promising results: A year of adjuvant atezolizumab led to significant improvement in disease-free survival in the same patient population. This finding prompted the recent FDA approval of adjuvant atezolizumab in this setting.
While we await the formal publication of KEYNOTE-091, one distinction in the design of these two studies is the positioning of adjuvant chemotherapy — an established standard of care for patients with resected stage IB-IIIA NSCLC that is associated with a modest but consistent survival benefit. Specifically, the IMpower010 trial randomly assigned patients only after they had received adjuvant chemotherapy, while KEYNOTE-091 did not require it, an approach that may be framed as reflecting “real-world practice.”
KEYNOTE-091 is not the only recent clinical trial to forgo adjuvant cisplatin-based chemotherapy in its design. Take the randomized trial of gefitinib vs adjuvant chemotherapy in EGFR mutation–positive Chinese patients with resected stage IB-IIIA NSCLC. The trial omitted adjuvant chemotherapy in the investigational arm, even though chemotherapy has been shown to confer a significant improvement in overall survival — a benefit we have not yet seen from adjuvant EGFR inhibitors. The same logic applies to the 2020 ADAURA trial of adjuvant Osimertinib.
This shift away from adjuvant chemotherapy in clinical trials reflects real-world practice. Studies show considerable geographic variation in the use of adjuvant chemotherapy across the United States, with carboplatin-based doublets often selected instead of cisplatin-based regimens.
However, these practices do not reflect evidence-based guidelines. The clinical practice guidelines from the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology have unequivocally directed eligible patients with resected stage IB-IIIA NSCLC to first pursue cisplatin-based chemotherapy on the basis of a decade’s worth of trials demonstrating a consistent benefit. And comparator arms in studies like the Intergroup-run ECOG 1505 trial use cisplatin-based doublet chemotherapy for four cycles, not best supportive care.