Abstract
In the phase III IMpower-010 trial, patients with non–small cell lung cancer whose disease returned after surgery and adjuvant chemotherapy received a year of adjuvant therapy with the immune checkpoint inhibitor atezolizumab. Use of this drug was associated with a 34% reduction in the risk of disease progression compared with best supportive care among patients whose tumors expressed PD-L1. The benefit was even greater in patients with PD-L1 expression of at least 50%.
Add immunotherapy to the ranks of therapeutic strategies that increase disease-free survival (DFS) in certain patients with stage IB to IIIA non–small cell lung cancer (NSCLC) that has advanced following surgery and adjuvant chemotherapy.
In the randomized phase III IMpower-010 trial, a year of adjuvant therapy with the immune checkpoint inhibitor atezolizumab (Tecentriq; Genentech) was associated with a 34% reduction in the risk of disease progression compared with best supportive care among patients whose tumors expressed PD-L1 on at least 1% of cells.
“The greatest magnitude of disease-free survival benefit was observed in those patients with PD-L1 in at least 50% of tumor cells,” said Enriqueta Felip, MD, PhD, from the Vall D'Hebron Institute of Oncology in Barcelona, Spain, who presented this finding at the European Society for Medical Oncology (ESMO) Congress 2021, held September 16–21. In that group, atezolizumab was associated with a 57% reduction in the risk of disease progression.
Outcomes from the trial in patients 65 and older were first reported at the 2021 American Society of Clinical Oncology Annual Meeting, and the first interim DFS analysis, the trial's primary endpoint, was reported at the International Association for the Study of Lung Cancer 2021 World Conference on Lung Cancer (WCLC) a few days before—and published concurrently with—ESMO (Lancet 2021 Sept 20 [Epub ahead of print]).
Investigators have noted that more than half of all patients with operable NSCLC subsequently treated with adjuvant chemotherapy will experience a relapse. Various strategies to improve DFS following recurrence include adjuvant chemotherapy with cisplatin plus either vinorelbine, pemetrexed, or bevacizumab, but none of these combinations has shown more than a small improvement in DFS over observation in the overall population.
In the ADAURA trial, patients with operable NSCLC with EGFR mutations who received 3 years of adjuvant therapy with the EGFR inhibitor osimertinib (Tagrisso; AstraZeneca) reduced their risk for disease recurrence or death by more than 90% compared with placebo. However, only about one third of patients harbor EGFR mutations.
Now, in the IMpower-010 trial, patients with completely resected stage IB–IIIA NSCLC were randomly assigned to either atezolizumab every 21 days for 16 cycles (507 patients), or best supportive care, generally observation and regular scans for disease recurrence (498 patients).
The study assessed DFS in three groups: patients with stage II–IIIA disease with PD-L1 expression of at least 1%, all patients with stage II–IIIA disease, and the intention-to-treat (ITT) population which included patients with stage IB NSCLC. After a median follow-up of 32.2 months, patients with PD-L1 expression of at least 1% who received atezolizumab had a 34% reduction in the risk of disease progression, compared with those who received best supportive care. Among all stage II–IIIA patients and in the ITT population, the risk reductions were 21% and 19%, respectively. Overall survival (OS) data were not mature at the time of cutoff in January 2021.
In the ITT population, Felip reported that locoregional-only relapses occurred in 37.8% of patients on atezolizumab and 36.9% of patients on best supportive care. Distant-only relapses occurred in 42.9% and 40.4%, respectively. Patients tolerated atezolizumab well, and no new safety concerns were identified.
ESMO discussant Benjamin Besse, MD, of the Gustave Roussy Cancer Center in Villejuif, France, commented that “what we already knew before this presentation [based on the WCLC] was that the trial is positive in stage II–IIIA in all comers, but [now] in a subset analysis, no benefit in the PD-L1–negative tumors in the patients—almost half of the [trial] population.”
Patients who had had pneumonectomy and those with EGFR-mutated or ALK-positive tumors didn't benefit either. It's not yet known whether patients with stage IB disease will have a clinical benefit from adjuvant immunotherapy, Besse said.
“My take is that if approved, I would prescribe adjuvant atezo,” Besse commented, but added the caveat “until I see the OS curves,” suggesting that he will reserve final judgment about whether to continue prescribing it until OS data are mature. –Neil Osterweil
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