Adjuvant Atezolizumab Holds Its Own in NSCLC

The latest update from the phase III IMpower010 trial suggests that adjuvant atezolizumab (Tecentriq; Genentech) may improve not only disease-free survival (DFS) but also overall survival (OS) in a subset of patients with non–small cell lung cancer (NSCLC).

Last year, study investigators showed that, following surgery and adjuvant chemotherapy, receiving atezolizumab for a year reduced disease progression risk by 34% in patients with tumor PD-L1 levels of at least 1% compared with best supportive care (Lancet 2021;398:1344–57). The benefit was even greater—57%—for those with PD-L1 expression of 50% or higher. Based on these results, various agencies greenlighted adjuvant atezolizumab as a treatment option for stage II/IIIA NSCLC, albeit with different PD-L1 positivity thresholds: at least 50% in Europe and at least 1% in the United States, China, and Japan.

During the International Association for the Study of Lung Cancer's 2022 World Conference on Lung Cancer in Vienna, Austria, August 6–9, data from the first interim OS analysis of IMpower010 were highlighted. Enriqueta Felip, MD, PhD, of Vall d'Hebron Institute of Oncology in Barcelona, Spain, reported that among 476 patients with PD-L1 expression of at least 1%, adjuvant atezolizumab decreased the risk of death by 29% compared with best supportive care. OS rates at 60 months were 76.8% and 67.5%, respectively; median OS was not reached in either arm.

“We're seeing a trend toward OS improvement” with atezolizumab, Felip said, “and this seems to be true across different subgroups” based on history of tobacco use, chemotherapy regimen, and surgery type.

Although prior findings indicated a DFS benefit with atezolizumab in two other groups—all patients with stage II/IIIA NSCLC and the intention-to-treat (ITT) population—“we didn't observe OS signals here,” Felip said. She cautioned, however, that analyses are ongoing, and, in the ITT cohort, “one issue is the inclusion of patients with stage IB disease, who have a better prognosis.”

Zeroing in on 209 patients with tumor PD-L1 expression levels of 50% or higher and no EGFR or ALK mutations, Felip noted that atezolizumab decreased the risk of death by 58% and seems to have lowered the risk of brain metastases. This is “clinically meaningful improvement,” she said, and notably, “almost exactly the same as the DFS benefit we previously reported” for this subgroup.

Discussant Benjamin Besse, MD, of Institut Gustave Roussy in Villejuif, France, observed that IMpower010's “survival curves are separating more and more” with longer follow-up—“a very good sign.” Genentech is assessing a subcutaneous formulation of atezolizumab and recently reported noninferior pharmacokinetics with this delivery method versus intravenous infusion, which he called “very important” for IMpower010's patients, given the prescribed yearlong treatment.

To Besse, “we have enough evidence to use adjuvant immunotherapy in stage II/IIIA” NSCLC. But “we shouldn't ask too much of subgroup analyses,” he remarked; instead, “just use the data to generate hypotheses.” These could test, for instance, the utility and limitations of PD-L1 status in predicting therapeutic benefit, as well as the nature of relapse. “We still don't know if it's the same disease as the resected primary tumor or something different and whether PD-L1 expression changes,” he said.

Circulating tumor DNA (ctDNA) analyses and “other new tools for the unseen” that are able to pinpoint what CT scans and IHC can't will help illuminate this murky landscape, Besse said. “In prescribing adjuvant therapy, we're really targeting a risk of relapse, not visible metastases,” he added. “So, I think we'll need to customize treatment based on ctDNA testing” of molecular residual disease, because “what's circulating is probably the most aggressive component” of early-stage NSCLC. –Alissa Poh

For more news on cancer research, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.