Formal discussant of the ­KEYNOTE-189 and KEYNOTE-407 trials, Mary O’Brien, MD, Head of the Lung Unit, Royal Marsden Hospital, NHS Foundation Trust, London, found that both studies showed consistent gains in overall and progression-free survival with pembrolizumab/chemotherapy, but she expressed some concerns. In both trials (and in other immunotherapy trials she cited), a waning phenomenon was evident from years 3 to 4 of about 8% and from years 4 to 5 of about 3% to 4%.

“The early separation of curves does not seem to hold up,” Dr. O’Brien told listeners. “At 5 years, in both KEYNOTE 189 and KEYNOTE-407, we see a 10% gain in overall survival for pembrolizumab/chemotherapy,” she noted. “The data from KEYNOTE-407 are the best squamous data we have to date and include the highest response rates seen for squamous metastatic non–small cell lung cancer.”

Mary O’Brien, MD

On the other hand, Dr. O’Brien noted that single-agent immunotherapy is “holding up” in terms of survival for patients whose tumors express PD-L1 (≥ 50%). “This is equivalent to combination immunotherapy plus chemotherapy,” she stated, calling into question the need for chemotherapy.

“A total of 2 years of treatment [with pembrolizumab/chemotherapy] is a good standard. Around 10% who complete 35 cycles [of immunotherapy/chemotherapy] are potentially cured,” she added.

Turning to toxicities with the combination, Dr. O’Brien commented: “We need more granularity on the toxicities.” 

DISCLOSURE: Dr. O’Brien reported financial relationships with AstraZeneca, Merck, Iteos, Puma, Sanofi, Pharmamar, and Sanofi.