Marina Chiara Garassino, MD

“TODAY WE HAVE good news, because IMpower 150 is another clear positive trial on the combination of chemotherapy with immunotherapy. This is true in terms of progression-free and overall survival, which are both statistically significant [for atezolizumab (Tecentriq) plus bevacizumab (Avastin) plus a platinum doublet vs bevacizumab plus a platinum doublet],” said formal discussant Marina Chiara Garassino, MD, of the Istituto Nazionale dei Tumori, Milan, Italy. 

Although Dr. Garassino admitted indirect historical comparisons of clinical trials are “dangerous,” she noted that progression-free survival was similar in both IMpower 150 and KEYNOTE-189, which compared pembrolizumab (Keytruda) plus chemotherapy vs chemotherapy in nonsquamous non–small cell lung cancer (NSCLC).“However, looking at overall survival, there is a superior incremental effect of immunotherapy with cisplatin and pemetrexed [Alimta] in KEYNOTE-189 compared with IMpower 150,” she continued. “Both results are from interim analyses, but the data are more mature in IMpower 150.” Dr. Garassino suggested that the combination of cisplatin and pemetrexed has a more immunogenic interaction with checkpoint inhibitor than the chemotherapy used in IMpower 150 and noted that future trials will shed some light on this issue. 

“Indirect comparisons are the only comparisons we can make to draw conclusions for our clinical practice tomorrow. For patients with PD-L1 expression between 1% and 49% and more than 50%, if you want to add chemotherapy, add cisplatin/pemetrexed—but not carboplatin plus taxane plus bevacizumab—based on the present evidence,” she stated. 

Subgroups Benefit Too 

Justin Gainor, MD

“THIS IS AN important trial providing further evidence that combining chemotherapy with a checkpoint inhibitor improves outcomes in NSCLC. It’s unique in showing that epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-mutated subgroups benefited from the combination, because in randomized trials, single checkpoint inhibitor did not benefit these groups over chemotherapy,” said Justin Gainor, MD, Assistant Professor at Massachusetts General Hospital and Harvard Medical School, Boston. “This is the first time we have seen a benefit for chemotherapy plus bevacizumab plus immunotherapy in these subgroups. KEYNOTE-189 excluded these patients.” 

Regarding the respective chemotherapy backbones of KEYNOTE-189 and IMpower 150, Dr. Gainor said the toxicity profiles of the two different regimens differ. “It is more common in the United States to use platinum/pemetrexed than carboplatin/paclitaxel/bevacizumab,” he continued. 

“Putting these data together, clinicians will use pembrolizumab plus platinum plus pemetrexed as the standard, based on KEYNOTE-189. I don’t think that IMpower 150 changes the current platform for newly diagnosed metastatic NSCLC, at least not for me. It does look like the hazard ratio for survival was more impressive in KEYNOTE-189 than in IMpower 150,” he concluded. ■

DISCLOSURE: Dr. Garassino reported no conflicts of interest. Dr. Gainor has served as a compensated consultant or received honoraria from Bristol-Myers Squibb, Genentech, Roche Ariad, Takeda, Pfizer, Merck, Regeneron, Oncorus, Agios, Amgen, Incyte, Array Biopharma, and Loxo Oncology.