Formal discussant Mary O’Brien, MD, Head of the Lung Unit, the Royal Marsden Hospital, NHS Foundation Trust, London, commented on the POSEIDON trial.

“The POSEIDON trial is the largest data set we have on KRAS-mutated [non–small cell lung cancer], with a positive signal in picking up some patients who would derive the greatest benefit from chemotherapy/immunotherapy. KRAS, KEAP1, and STK11 appear to predict better outcomes for durvalumab/tremelimumab plus chemotherapy vs chemotherapy,” Dr. O’Brien said, but she added this was not found in two other recent trials of different regimens.

Mary O’Brien, MD

With tremelimumab, durvalumab, and chemotherapy, 25.8% of those with STK11 mutations were alive at 3 years; 30% of those with KEAP1 mutations were alive at 3 years; and 40% of those with KRAS mutations were alive at 3 years.

“The survival trends suggest that a limited course of tremelimumab plus durvalumab plus chemotherapy is beneficial in those patients with these harder-to-treat mutations,” she stated.

“I want to stress that the experimental regimen [in POSEIDON] included a short course of the CTLA-4 inhibitor [tremelimumab]. The survival curves and progression-free survival curves don’t separate early, but there is a dropoff of about 5% from 3 to 4 years.

“We need much more granularity on the toxicities. Patient-reported outcomes will help, but I still I think we need new tools, such as biomarkers for organ-specific toxicity,” Dr. O’Brien told the audience. 

DISCLOSURE: Dr. O’Brien reported no conflicts of interest.