Adjuvant immunotherapy with atezolizumab after standard chemotherapy improved disease-free survival and time to locoregional and distant relapse compared with best supportive care in prespecified subgroups of patients with stage II to IIIA non–small cell lung cancer (NSCLC), according to an exploratory analysis of the phase III IMpower010 trial presented during the European Society for Medical Oncology (ESMO) Congress 2021.¹ Specifically, atezolizumab improved disease-free survival and relapse at any site in patients whose tumors expressed PD-L1, including those with EGFR and ALK aberrations, with the greatest benefit in PD-L1–high expressors (ie, ≥ 50%).

These results reinforce the significant disease-free survival benefit gained with adjuvant atezolizumab in this population seen in an interim analysis of the same trial published earlier this year.² The earlier analysis showed a significant disease-free survival benefit withadjuvant atezolizumab vs best supportive care following adjuvant platinum-based therapy in patients whose tumors expressed PD-L1 ≥ 1% (34% improvement) as well as in all randomly assigned patients with stage II to IIIA disease (21% improvement). The improvement in disease-free survival was not statistically significant in the intention-to-treat population, but disease-free survival and overall survival will continue to be analyzed.

A post hoc descriptive analysis of IMpower010 showed that the median time to relapse was 17.6 months with atezolizumab vs 10.9 months with best supportive care, suggesting that the immunotherapy delayed the time to relapse.

“The greatest magnitude of disease-free survival benefit was observed in those patients with PD-L1 in at least 50% of tumor cells.”

— Enriqueta Felip, MD

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“The greatest magnitude of disease-free survival benefit was observed in those patients with PD-L1 in at least 50% of tumor cells. At this disease-free survival interim analysis, similar patterns of relapse were seen between the study arms, and the time to relapse appeared to favor atezolizumab vs best supportive care in this group of patients with stage II to IIIA, PD-L1–positive tumors,” said lead author Enriqueta Felip, MD, Head of the Thoracic and Head and Neck Cancer Unit of Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona.

Based on the IMpower010 data, the U.S. Food and Drug Administration (FDA) granted priority review to atezolizumab as an adjuvant treatment following surgery plus platinum-based chemotherapy in patients with NSCLC whose tumors express PD-L1 ≥ 1%. Atezolizumab is already FDA-approved in the metastatic NSCLC setting. Taken together, evidence to date suggests that atezolizumab will likely be approved as adjuvant therapy in earlier-stage disease.

**Atezolizumab (Tecentriq) is now approved for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non–small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test. See related FDA update here. 

Study Background

Following treatment with curative intent, up to 60% of patients with stage I to III NSCLC will experience relapse, and new strategies are needed for this population. Recently, the ADAURA trial found that adjuvant therapy with osimertinib improved survival in patients with stage II to IIIA disease and EGFR expression.³

“Impower010 is the first phase III study to demonstrate disease-free survival improvement with immunotherapy in the adjuvant NSCLC setting after complete resection and platinum-based chemotherapy,” Dr. Felip stated.

Study Details

The IMpower010 trial enrolled 1,280 patients with fully resected stage IB to IIIA NSCLC treated with one to four cycles of platinum-based chemotherapy. Of those patients, 1,105 were randomly assigned to receive either atezolizumab at 1,200 mg every 3 weeks for 1 year or best supportive care.

All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, underwent lobectomy or pneumonectomy, and provided tumor tissue samples for PD-L1 analysis. The median age of patients was 62, and 38% were 65 or older. Two-thirds were male, 73.4% were white, and 55.3% had an ECOG performance score of 0. Two-thirds had nonsquamous histology, 12% had stage IB disease, and 54% had PD-L1 expression ≥ 1%.

In the primary analysis, at a median follow-up of 32.2 months, the median disease-free survival in all randomly assigned patients with stage II to IIIA disease was 42.3 months for atezolizumab vs 35.3 months for best supportive care (P = .02). In the intent-to-treat population, median disease-free survival was not reached with atezolizumab vs 37.2 months for best supportive care (P = .04).

Grade 3 or 4 treatment-related adverse events were reported in 53 patients (11%), and grade 5 events were seen in 4 patients (1%) of 495 patients randomly assigned to atezolizumab.

Overall survival data are immature, and those results are eagerly awaited, Dr. Felip noted.

Exploratory Findings

During the ESMO Congress 2021, Dr. Felip presented data from an exploratory analysis of the time to relapse and subsequent treatment in these patient populations. Disease-free survival was hierarchically tested in the following three populations: those with stage II to IIIA NSCLC and PD-L1 > 1%; all-randomized stage II to IIIA population; intent-to-treat population (all randomly assigned patients including those with stage IB).

Disease-free survival by PD-L1 status showed that in the patients with stage II to IIIA disease (n = 882) with PD-L1 expression of 1% to 49%, including patients with EGFR and ALK aberrations, the benefit of atezolizumab was of lesser magnitude, with a 13% improvement vs best supportive care. In patients with PD-L1 expression ≥ 50%, the disease-free survival hazard ratio was 0.43 (95% CI = 0.27–0.68). Among those with stage II to IIIA NSCLC and PD-L1 expression of 1% to 49%, the disease-free survival hazard ratio was 0.87 (95% CI = 0.60–1.26). In the patient subgroup without EGFR and ALK aberrations (part of a post hoc analysis), the disease-free survival benefit was improved by 18% with atezolizumab vs best supportive care.

“Impower010 is the first phase III study to demonstrate disease-free survival improvement with immunotherapy in the adjuvant NSCLC setting after complete resection and platinum-based chemotherapy.”

— Enriqueta Felip, MD

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“This tells us that patients with PD-L1 of 1% to 49% probably benefit less from immunotherapy as monotherapy than patients whose tumors have high PD-L1 expression. In my opinion, for these patients, it’s an opportunity to consider the regimen and individualize treatment according to other variables, such as risk of recurrence,” Dr. Felip said.

In an exploratory analysis with disease recurrence as the sole event for disease-free survival, disease relapse rates for the PD-L1 ≥ 1% group were 29.4% with atezolizumab and 44.7% with best supportive care. Among all randomly assigned patients with stage II to IIIA NSCLC, the disease relapse rate was 33% for atezolizumab vs 43% for best supportive care. In the intent-to-treat population with stage IB to IIIA disease, disease relapse rates were 30.8% and 40.8%, respectively.

There were no clear differences in relapse patterns related to stage or PD-L1 expression levels. Locoregional-only relapse was reported in 47.9% of atezolizumab-treated patients and 41.2% of best supportive care–treated patients with PD-L1 ≥ 1% stage II to IIIA disease. In the all-randomized stage II to IIIA population, locoregional-only relapse rates were 39.5% vs 38.1%, respectively. In the intent-to-treat population, those relapse rates were 37.8% vs 36.9%, respectively.

In the PD-L1 ≥ 1%, distant-only relapse rates were 38.4% with atezolizumab and 39.2% with best supportive care. Among all randomly assigned patients, distant relapse rates were 42.2% and 40.7%, respectively. In the intent-to-treat stage IB to IIIA group, these rates were 42.9% vs 40.4%, respectively.

“Note that only 29% to 33% of patients in the atezolizumab arm relapsed vs 41% to 44% in the best supportive care arm,” she pointed out.

A post hoc descriptive analysis of the time to relapse showed that among PD-L1–positive patients, the median time to locoregional and distant relapse was 24 months with atezolizumab vs 5.3 months with best supportive care. Central nervous system–only relapse occurred at a median of 18.2 months vs 10.6 months, respectively.

No clear differences in median time to relapse in the two treatment arms were observed in the other two populations (all-randomized stage II to IIIA and intent-to-treat population including those with stage IB disease).

Approximately 65% of patients had additional systemic therapy at recurrence, and the type of systemic therapy in the three study populations and two treatment arms were well balanced. As expected, more immunotherapy was given in the best supportive care arm: about 32% of patients received immunotherapy compared with about 12% of the atezolizumab arm. No differences between the two treatment arms were observed across the three study populations regarding the use of radiation therapy and surgery post relapse. 

DISCLOSURE: Dr. Felip has served in an advisory role or in a speakers bureau for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffman-La Roche, GlaxoSmithKline, Janssen, Medscape, Merck KGaA, Merck Sharp and Dohme, Novartis, Peptomyc, PeerVoice, Pfizer, Regeneron, Sanofi Genzyme, -Syneos Health, Seattle Genetics, Takeda, and Touch Medical; is an independent board member of Grifols; and has received research funding from Fundación Merck Salud, Grant for Oncology Innovation, and Merck Healthcare KGaA.

REFERENCES

1. Felip E, Vallieres E, Zhou C, et al: IMpower010: Sites of relapse and subsequent therapy from a phase 3 study of atezolizumab vs best supportive care after adjuvant chemotherapy in resected stage IB-IIIA NSCLC. ESMO Congress 2021. Abstract LBA9. Presented September 20, 2021.

2. Wakelee HA, Altorki N, Zhou C, et al: IMpower010: Primary results of a phase III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected stage IB-IIIA non-small cell lung cancer. 2021 ASCO Annual Meeting. Abstract 8500.

3. Wu YL,Tsuboi M, He J, et al: Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med 383:1711-1723, 2020.