FDA Approves Adjuvant Atezolizumab for Select Stage II to IIIA NSCLC

FDA

The FDA has approved atezolizumab (Tecentriq) for use as an 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% or more of tumor cells, as determined by an FDA-approved test.¹

The regulatory agency also gave the green light to the VENTANA PD-L1 (SP263) Assay, developed by Ventana Medical Systems, Inc., for use as a companion diagnostic device to select patients with NSCLC for adjuvant treatment with atezolizumab.

The decision was supported by data from the phase 3 IMpower010 trial (NCT02486718), which showed that the median disease-free survival (DFS) was not yet reached (95% CI, 36.1–not evaluable [NE]) in patients with stage IB through stage IIIA NSCLC who received treatment on the atezolizumab arm (n = 248) vs 35.3 months (95% CI: 29.0–NE) in those who were on the best supportive care (BSC) arm (n = 228; hazard ratio [HR], 0.66; 95% CI, 0.50-0.88; P = .004).²

Moreover, in a prespecified secondary subgroup analysis of patients with stage II to IIIA NSCLC who had a PD-L1 tumor cell expression of 50% or higher (n = 229), the HR for DFS was 0.43 (95% CI, 0.27-0.68). In an exploratory subgroup analysis of patients who had a PD-L1 tumor cell expression ranging from 1% to 49% (n = 247), the HR for DFS was 0.87 (95% CI, 0.60-1.26).³

"[Atezolizumab] is now the first and only cancer immunotherapy available for adjuvant treatment of NSCLC, introducing a new era where people diagnosed with early lung cancer may have the opportunity to receive immunotherapy to increase their chances for cure,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, stated in a press release.⁴ “Today’s landmark approval gives physicians and patients a new way to treat early lung cancer that has the potential to significantly reduce risk of cancer recurrence, after more than a decade with limited treatment advances in this setting.”

IMpower010 enrolled patients with completely resected stage IB to IIIA NSCLC who had an ECOG performance status of 0 to 1, a lobectomy/pneumonectomy, and 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. Then, 1005 participants were randomized 1:1 to receive either atezolizumab at 1200 mg every 21 days for 16 cycles or BSC. Crossover was not permitted.

Patients were stratified based on sex (male vs female), stage (IB vs II vs IIIA), histology, and 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 trial were investigator-assessed DFS which was tested hierarchically: patients with stage II to IIIA disease and a PD-L1 expression of 1% or higher, all-randomized patients with stage II to IIIA disease, and the intent-to-treat (ITT) population with stage IB to IIIA disease. Secondary end points included overall survival (OS) in the ITT population, DFS in patients with stage II to IIIA disease who have a PD-L1 expression of 50% or higher, as well as 3- and 5-year DFS in all 3 populations.

Among 1005 patients, the median age was 62 years (range, 26-84), and 38.0% of patients were 65 years of age or older. Moreover, most patients were male (66.9%), White (73.4%), and current or previous smokers (77.9%) and had an ECOG performance status of 0 (55.3%) and nonsquamous histology (65.6%). Moreover, 41.1% of patients had stage IIIA disease, 29.4% had stage IIA disease, 17.3% had stage IIB disease, and 12.2% had stage IB disease.

More than half of patients did not have tumors that harbored an EGFR mutation (52.4%) or an ALK rearrangement (57.1%). Notably, 54.6% of patients had a PD-L1 tumor cell expression of 1% or higher by SP263.

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 with atezolizumab (n = 442) was 42.3 months (95% CI, 36.0–NE) vs 35.3 months (95% CI, 30.4-46.4) with BSC (n = 440) in the all-randomized stage II to IIIA population HR, 0.79; 95% CI, 0.64-0.96; P = .02).

In the ITT population, the median DFS in the investigative (n = 507) and control (n = 498) arms was not evaluable (95% CI, 36.1–NE) and 37.2 months (95% CI, 31.6–NE), respectively (HR, 0.81; 95% CI, 0.67-0.99; P = .04). The DFS in this population did not cross the significance boundary at the interim DFS analysis.

Early OS data from the interim analysis showed that the HR was 0.77 (95% CI, 0.51-1.17) in the subset of patients with stage II to IIIA disease and a PD-L1 expression of 1% or higher, 0.99 (95% CI, 0.72-1.33) in the all-randomized population with stage II to IIIA disease, and 1.07 (95% CI, 0.80-1.42) in the ITT population.

The adverse effects that were most frequently reported in patients who received atezolizumab included increased aspartate aminotransferase, blood creatinine, and alanine aminotransferase. Other toxicities included hyperkalemia, rash, cough, hypothyroidism, pyrexia, fatigue/asthenia, musculoskeletal pain, peripheral neuropathy, arthralgia, and pruritus.

References

1. FDA approves atezolizumab as adjuvant treatment for non-small cell lung cancer. News release. October 15, 2021. Accessed October 15, 2021. https://bit.ly/3lHUgvQ
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
3. 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. Ann Oncol. 2021;32(suppl 5):S1319. doi:10.1016/j.annonc.2021.08.2120
4. US FDA approves Roche's Tecentriq as adjuvant treatment for certain people with early non-small cell lung cancer. News release. Roche. October 15, 2021. Accessed October 15, 2021. https://bit.ly/3BMUGXy