Using criteria for selection of immunotherapy, only 2 to 3 patients out of 10 would be eligible. To translate this into clinical practice, the pool of patients has to be enlarged to combine immunotherapy with chemotherapy.

— Jean-Charles ­Soria, MD, PhD

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Formal discussant Jean-Charles ­Soria, MD, PhD, of Institut Gustave Roussy, Villejuif, France, and Editor-in-Chief of Annals of Oncology (the official journal of the European Society for Medical Oncology [ESMO]), tried to put these findings into perspective. He pointed out that when applying the inclusion criteria, only about 50% of patients with non–small cell lung cancer (NSCLC) were considered for pembrolizumab and chemotherapy in the front-line setting. This was due to various exclusion criteria, including poor performance status, brain metastases, autoimmune disorders, and tissue availability for PD-L1 (programmed cell death ligand 1) staining.

“The PD-1 [programmed cell death protein 1] antibody is a new standard of care on the basis of KEYNOTE-024 results, but for which patients? Using criteria for selection of immunotherapy, only 1 to 2 patients out of 10 would be eligible. To translate this into clinical practice, the pool of patients has to be enlarged to combine immunotherapy with chemotherapy,” he told listeners.

Dr. Soria noted that the response rates were almost double in patients treated with pembrolizumab ­(Keytruda) plus chemotherapy but said the numbers of patients were too small to draw firm conclusions about PD-L1 expression as a biomarker for selection.

Cautious Optimism

“We know that positive phase II trials do not guarantee positive phase III trials. We need to be cautious in interpreting these results. The study was not adequately powered to draw conclusions. Even if the phase III trials are positive, we still exclude 50% of all patients with NSCLC with current criteria. Perhaps we should be using immunotherapy for performance status 2 patients,” Dr. Soria continued.

“The race is on: pembrolizumab as monotherapy in the front-line setting, the combination of pembrolizumab and chemotherapy, vs other approaches by competitors. The question is who will come in first of the three approaches: selecting patients by PD-L1 expression, combining immunotherapy with CTLA-4 [cytotoxic T-lymphocyte–associated protein 4] agents, or combining immunotherapy with chemotherapy,”

“We can rejoice. We have at least 11 different clinical trials sponsored by 4 different companies in the front-line setting of NSCLC to answer these questions,” shared Dr. Soria.

“When we assess the magnitude of benefit with immunotherapy, we need good health economic analyses. Perhaps fewer cycles than 35 are needed, because the median number in clinical trials is 11 cycles. Patients who get anti–PD-1 and PD-L1 therapy will not need growth factor support (erythropoietin and granulocyte colony-stimulating factor), which currently accounts for 5 to 10 billion Euros [approximately between $7 and $14 billion US] in health-care costs,” Dr. ­Soria reminded the audience. ■

Disclosure: Dr. Soria is a consultant for AstraZeneca, Astex, Clovis, GlaxoSmithKline, Gammamabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, Pharmamar Pierre Fabre, Roche-Genentech, Sanofi, Servier, Symphogen, and Takeda.