Expert Point of View: Michael Boyer, MBBS, PhD
“The OAK subgroup analyses showed the benefit of atezolizumab (Tecentriq) virtually “across the board,” including among patients with programmed cell death ligand 1 (PD-L1)–negative tumors, remarked invited discussant, Michael Boyer, MBBS, PhD, Chief Clinical Officer and Conjoint Chair of Medical Oncology (Thoracic Oncology) at the Chris O’Brien Lifehouse, Sydney, Australia.
However, the antibody used for immunohistochemistry, SP142, performed somewhat differently from the three others in use, as established in the Blueprint study,1 he noted. “There is a group of patients who score effectively zero on the SP142 antibody but with any other antibody would have expression of 5% or 10%. So as we interpret the meaning of those PD-L1–negative findings, we need to bear that in mind,” elaborated Dr. Boyer.
Additionally, patients in the similar phase II POPLAR study with PD-L1–negative tumors identified in the same way did not see better survival with atezolizumab.2 “It’s unclear to me why the [OAK] results differ from the POPLAR data,” Dr. Boyer admitted.
What will happen as we use these drugs first line and take out the group that benefits the very most—those with high PD-L1 expression—remains an open question.— Michael Boyer, MBBS, PhD
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Words of Caution
Some of the findings, such as those for patients with central nervous system (CNS) metastases, were based on small numbers of patients, and confidence intervals were often overlapping. “This just tells us to be cautious when looking at subgroup analyses, particularly multiple subgroup analyses, of randomized trials. They give us ideas for future study designs, but they don’t tell us exactly who will and won’t benefit,” acknowledged Dr. Boyer. Also, “there are some limitations here, because we have looked at a whole series of univariate analyses with things that clearly are related; for example, smoking and epidermal growth factor receptor (EGFR) mutations are not independent of one another.”
Although atezolizumab improved survival at all levels of PD-L1 expression, its efficacy clearly increased with PD-L1 expression, Dr. Boyer pointed out. “That will be important, because it’s likely to drive differences in cost-effectiveness, which are certainly going to be important in my country [Australia] if not in other countries.”
Finally, “what will happen as we use these drugs first line and take out the group that benefits the very most—those with high PD-L1 expression—remains an open question,” he concluded.■
Disclosure: Michael Boyer, MBBS, PhD, has received research support from Genentech/Roche, Pfizer, Eli Lilly, Merck Sharpe and Dohme, AstraZeneca, and Clovis.
1. Hirsch FR, Philip S, Averbuch SD, et al: The Blueprint Project: Harmonizing companion diagnostics across a class of targeted therapies. 2016 AACR Annual Meeting. Presented April 19, 2016.
2. Fehrenbacher L, Spira A, Ballinger M, et al: Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): A multicentre, open-label, phase 2 randomised controlled trial. Lancet 387:1837-1846, 2016.
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