FDA Grants Priority Review to Adjuvant Atezolizumab for PD-L1+ Early-Stage NSCLC

The FDA has granted priority review to a supplemental biologics license application (sBLA) for atezolizumab (Tecentriq) as an adjuvant treatment after surgery and platinum-based chemotherapy in patients with non–small cell lung cancer (NSCLC) whose tumors have a PD-L1 expression of 1% or higher per an FDA-approved test.¹

The application is supported by findings from the phase 3 IMpower010 trial (NCT02486718) which showed that when atezolizumab was administered after surgery and platinum-based chemotherapy, it resulted in a 34% reduction in the risk of disease recurrence or death vs best supportive care (BSC; HR, 0.66; 95% CI, 0.50-0.88; P = .004) in patients with stage II to IIIA disease and a PD-L1 tumor expression of 1% or higher.²

At a median follow-up of 32.8 months (range, 0.1-57.5), the median disease-free survival (DFS) had not yet been reached (95% CI, 36.1–not evaluable [NE]) with atezolizumab vs 35.3 months (95% CI, 29.0-NE) with BSC.

Follow-up for the trial will continue with planned analyses of DFS in the intent-to-treat (ITT) population, which includes patients with stage IB disease. Analyses are also planned regarding overall survival (OS).

The regulatory agency is reviewing the sBLA under the Real-Time Oncology Review pilot programme, and the FDA is anticipated to decide by December 1, 2021.

“New treatment options are urgently needed in early-stage NSCLC to help the nearly 50% of people who currently experience a recurrence following surgery,” Levi Garraway, MD, PhD, chief medical officer, and head of Global Product Development at Roche, stated in a press release. “[Atezolizumab] is the first cancer immunotherapy to show a clinically meaningful benefit in the adjuvant lung cancer setting, and we’re working closely with the FDA to bring this significant advancement to patients as quickly as possible.”

The phase 3 trial enrolled patients with completely resected stage IB to IIIA NSCLC, an ECOG performance status of 0 to 1, who have undergone lobectomy/pneumonectomy, and who had tumor tissue available for PD-L1 analysis.

A total of 1280 patients received cisplatin plus pemetrexed, gemcitabine, docetaxel, or vinorelbine for 1 to 4 cycles and then 1005 patients were randomized 1:1 to receive either atezolizumab at 1200 mg every 21 days or BSC. Patients were stratified based on sex (male vs female), disease stage (IB vs II vs IIIA), PD-L1 tumor expression status (TC2/3 and any IC vs TC0/1 and IC2/3 vs TC0/1 and IC0/1).

The primary end points of the research were investigator-assessed DFS tested hierarchically in patients with a PD-L1 tumor cell expression of 1% or higher, all randomized patients with stage II to IIIA disease, and the ITT population of those with stage IB to IIIA disease. Important secondary end points comprised OS in the ITT population, DFS in those with PD-L1 tumor cell expression of 50% or higher and stage II to IIIA disease, as well as 3- and 5-year DFS rates in all 3 patient populations.

The median age of study participants was 62 years (range, 26-84), with 38.0% of patients 65 years of age or older. Additionally, 66.9% of patients were male, 73.4% were White, and 55.3% had an ECOG performance status of 0. Moreover, 65.6% of patients had non-squamous histology, 12.2% had stage IB disease, and 54.6% had a PD-L1 tumor cell expression of 1% or higher.

Additional data presented during the 2021 ASCO Annual Meeting showed that at a median follow-up of 32.2 months (range, 0.57-5), the median DFS in the all-randomized stage II to IIIA population in the investigative and control arms was 42.3 months (95% CI, 36.0–NE) vs 35.3 months (95% CI, 30.4-46.4), respectively (HR, 0.79; 95% CI, 0.64-0.96; P = .02).

At a median follow-up of 32.2 months (range, 0.58-8), the median DFS with atezolizumab in the ITT population (n = 507) was not evaluable (95% CI, 36.1–NE) vs 37.2 months (95% CI, 31.6–NE) with BSC (HR, 0.81; 95% CI, 0.67-0.99; P = .04). However, the DFS in this population did not cross the significance boundary at the interim analysis.

The OS data were immature at the time of the preplanned DFS interim analysis, and the OS in the ITT population had not been formally tested. However, a trend toward an OS improvement with atezolizumab was observed in the population of patients with stage II to IIIA with a PD-L1 tumor cell expression of 1% or higher (HR, 0.77; 95% CI, 0.51-1.17).

The safety profile of atezolizumab proved to be consistent with what has previously been reported with its single-agent use across indications and lines of therapy.

Any-cause adverse effects (AEs) were experienced by 92.7% of those who received atezolizumab (n = 495) and 70.7% of those given BSC (n = 495); 67.7% of these effects in the investigative arm were determined to be related to treatment. Moreover, grade 3 or 4 toxicities were observed in 21.8% vs 11.5% of those in the atezolizumab and BSC arms, respectively. Grade 5 effects were reported in 8 patients who received atezolizumab vs 3 patients who were given BSC.

Toxicities led to a dose interruption in 28.7% of patients who were administered atezolizumab, and 18.2% experienced AEs that resulted in treatment discontinuation.

References

1. US FDA grants priority to Roche’s Tecentriq as adjuvant treatment for certain people with early non-small cell lung cancer. News release. Roche. August 3, 2021. Accessed August 3, 2021. https://bit.ly/3jj5TXN
2. Wakelee HA, Altorki NK, 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 (NSCLC). J Clin Oncol. 2021;39(suppl 15):8500. doi:10.1200/JCO.2021.39.15_suppl.8500