Merck's pembrolizumab has overtaken Bristol-Myers Squibb (BMS)'s nivolumab for the first-line treatment of non-small-cell lung cancer (NSCLC), shows data presented at the European Society for Medical Oncology (ESMO) meeting last month. But differences in trial design, and numerous ongoing trials of programmed cell death protein 1 (PD1) modulating antibodies paired with other drugs, mean that the fight for first-line settings has only just begun.

Merck tested its pembrolizumab in 305 patients with metastatic NSCLC and 'high' PD1 ligand 1 (PDL1) levels. Patients received either pembrolizumab as a monotherapy, or standard of care platinum-based chemotherapy. Pembrolizumab extended the progression-free survival by 4 months more than standard of care, impressing oncologists when the data were presented at ESMO and concurrently published in the New England Journal of Medicine .

BMS designed a broader trial with a lower PDL1 threshold, testing its nivolumab in 541 patients with advanced NSCLC and positive for PDL1 expression. Patients received either nivolumab as a monotherapy, or standard of care platinum-based chemotherapy. The trial failed on its primary end point, with nivolumab-treated patients averaging 1.7 fewer months of progression-free survival.

Shares in BMS plummeted over the summer when it announced the top-line data of its trial, wiping US$21 billion off the company's market capitalization as investors fretted over the loss of the first-line market. But, although Merck was a clear victor in this race for first-line dominance, its play-it-safe approach — to PDL1 expression and other factors such as lack of brain metastases, targetable mutations and prior steroid use — could limit roll-out of the drug. Merck's stringent patient-selection strategy would exclude approximately 90% of NSCLC patients in clinical practice, said Jean-Charles Soria, an oncologist at South-Paris University in France and a trial discussant at ESMO.

Further trials of PDL1 inhibitors in combination with other drugs, in NSCLC and other cancers, will yet determine the future of the first-line immunotherapy market.