Atezolizumab After Adjuvant Chemotherapy in Resectable NSCLC

Dr Martin Dietrich comments on the IMpower010 trial of atezolizumab versus best supportive care after adjuvant chemotherapy in patients with resected non–small cell lung cancer.

Mark A. Socinski, MD: Let’s transition to the data we saw from IMpower010. The phase III data that Heather Wakelee recently presented at ASCO [American Society of Clinical Oncology]. Martin, give us your thoughts on the findings in this trial.

Martin Dietrich, MD, PhD: I think this was a surgical ASCO, interesting data in [CheckMate] 816 and IMpower010. With enlarged randomized biomarker space with IO [immunotherapy] looking at over 1000 patients after complete resection and completion of adjuvant chemotherapy of 4 cycles of a cisplatin-based chemotherapy randomized to complete a year of atezolizumab [Tecentriq]. Looking at outcome data across the PD-L1 [programmed death-ligand 1] spectrum, we’ve seen PD-L1 negatives greater than 1% and greater than 50%. There was clearly a staggered benefit similar like we’ve seen and discuss early in the metastatic setting and then the PACIFIC trial as well. This could be a staggered benefit with a hazard ratio of 0.4 for PD-L1 greater than 50% with a hazard ratio of around 0.63, if I’m not mistaken, for greater than 1%. But buried in there is the 1% to 49% that probably turn out to be somewhere between 0.8 to 0.9, and then really no benefit for the PD-L1 negative. So, my take on this is biomarkers here do matter enough. I think this tie into the discussion about what is better, neoadjuvant or adjuvant chemotherapy with the discussions previously. We’re looking at probably a need for a comprehensive biomarker analysis upfront. We probably need PD-L1 levels in the beginning including EGFR, ALK, and other molecular drivers to really map out the optimal treatment plan afterwards. I really think that this is a regimen where I really would like to see the 1 to 49 subset data. Biologically, I’m impressed that even in the absence of macroscopic disease, and we actually still see immunotherapy responses. I would always think that the immune system needs a tumor microenvironment to actually train on a PD-1/PD-L1 access to activate lymphocytes. So, I think that was very reassuring to see, but it will need to be biomarker driven in the same way as we’ve had in the earlier stage disease. There was clearly an increase in benefit as we move into higher stage disease, higher nodule disease. Some of the data in the lower stages that were enrolled here was probably not mature yet. There was a trend for benefit but not necessarily positive. PD-L1 levels greater than 50% without drivers. And probably other options including neoadjuvant or adjuvant chemoimmunotherapy or combination immunotherapy strategies and to drive for those that are less than 50%. So, no new lessons from stage III and stage IV disease, but affirmed in basically in the surgical setting here. Biomarkers really drive the decision making here for optimal therapy. Otherwise, the data looks very impressive.


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