“Platinum-ineligible patients are typically excluded from clinical trials, yet they represent the majority of patients that we diagnose and treat—patients with poor performance status and comorbidities,” said invited discussant Natasha Leighl, MD, of the Princess Margaret Cancer Centre, Toronto. “The IPSOS trial was an extraordinary study, based on real-world practice. There was a doubling of 2-year overall survival, a near doubling of response rate, and a doubling of median duration of response [with atezolizumab],” she continued.

Natasha Leighl, MD

There were some minor imbalances in the trial, with more PD-L1–negative and more elderly patients with a performance status of 0 or 1 in the atezolizumab arm. “A total of 27% were young patients with a poor performance status; 16% were older with a good performance status; only about 8% had a performance status of 3, and 30% were at least 80 years old,” Dr. Leighl pointed out.

“The study is incredibly generalizable but is it reproducible? Atezolizumab performed spot on, and the chemotherapy arm did better than expected, even with a 19% crossover rate. This is the first ever trial of atezolizumab monotherapy in this population. There was no difference according to PD-L1 status, which makes me wonder what is going on,” she added. “Atezolizumab, compared to chemotherapy, caused minimal harm and no deterioration in quality of life. Patients in the atezolizumab arm had fewer treatment-related adverse events and fewer toxic deaths. While the budget impact could be major if we treat all these patients with first-line atezolizumab, the IPSOS trial results score 5 out of 5 using the ESMO clinical benefit scale,” she stated.

“This study should be easy to generalize to our practice, but there are lingering questions. With crossing of the survival curves, there may be different populations with differing outcomes in IPSOS…. Could some performance status 3 patients in IPSOS have been harmed by using initial chemotherapy rather than supportive care, the current standard for this group? This is also the first study of atezolizumab in lung cancer where no difference was [found] according to PD-L1 status, which makes me wonder what is going on in this diverse population and how we identify those who benefit most,” she added. “Overall, the IPSOS trial expands our knowledge of immunotherapy benefit in a larger real world population usually excluded from trials, with an important signal of long term benefit,” she concluded. 

DISCLOSURE: Dr. Leighl has received grants for clinical research from Amgen, Array BioPharma, AstraZeneca, EMD Serono, Guardant Health, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, and Roche.