FDA Approves Companion Diagnostic for Adjuvant Atezolizumab in Stage II to IIIA NSCLC

FDA

The FDA has approved the VENTANA PD-L1 (SP263) assay to assist in identifying which adult 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 are eligible to receive adjuvant atezolizumab (Tecentriq) following surgery and platinum-based chemotherapy.¹

Adjuvant atezolizumab was approved for use in this indication on October 15, 2021, based on findings from the phase 3 IMpower010 trial (NCT02486718).² Results indicated 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 disease who received atezolizumab (n = 248) vs 35.3 months (95% CI, 29.0–NE) in those who received best supportive care (BSC; n = 228; HR, 066; 95% CI, 0.50-0.88; P = .004).³

In a prespecified secondary subgroup analysis of patients with stage II to IIIA disease who had a PD-L1 tumor 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 expression ranging 1% to 49% (n = 247), the HR for DFS was 0.87 (95% CI, 0.60-1.26).⁴

VENTANA PD-L1 was used as part of the trial to identify patients whose tumors have PD-L1 expression.

“Early detection of lung cancer can change the treatment pathway for patients and give them more treatment options,” Thomas Schinecker, chief executive officer at Roche Diagnostics, stated in a press release. “We are proud to offer a companion diagnostic PD-L1 test that identifies [patients with] lung cancer who may qualify for [atezolizumab] therapy. With the FDA approval of this companion diagnostic test, clinicians now have an effective tool for offering better patient care through targeted immunotherapy treatment.”

Patients with completely resected stage IB to IIIA NSCLC who had an ECOG performance status of 0 to 1 were enrolled to IMpower010. To be eligible for enrollment, patients needed to have a lobectomy/pneumonectomy and tumor tissue available for PD-L1 analysis.

In total, 1280 participants received cisplatin plus pemetrexed, gemcitabine, docetaxel, or vinorelbine for 1 to 4 cycles. Then, 1005 patients were randomized 1:1 to receive either atezolizumab at 1200 mg every 21 days for 16 cycles or BSC. Patients on the control arm were not allowed to cross over to the investigative arm.

Stratification factors included sex (male vs female), stage (IB vs II vs IIIA), histology, and PD-L1 expression status (TC2/3 and IC vs TC0/1 and IC2/3 vs TC0/1 and IC0/1.

The primary end points of the trial were DFS per investigator assessment, 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. Key secondary end points comprised overall survival (OS) in the ITT population, DFS in patients with stage II to IIIA disease who have a PD-L1 expression of 50% higher, as well as 3- and 5-year DFS in all populations.

Among the patients who underwent randomization, the median age was 62 years (range, 26-84), with 38.0% of patients aged 65 years or older. Most patients were male (66.9%), White (73.4%), had an ECOG performance status of 0 (55.3%) and nonsquamous histology (65.6%). Regarding disease stage, 41.1% had stage IIIA disease, 29.4% had stage IIA disease, 17.3% had stage IIB disease, and 12.2% had stage IB disease.

Moreover, 52.4% had tumors that harbored EGFR mutations and 57.1% had ALK rearrangements. Of the patients enrolled, 54.6% had a PD-L1 tumor expression of 1% or higher per the VENTANA assay.

Additional findings presented during the 2021 ASCO Annual Meeting demonstrated that the median DFS with the immunotherapy (n = 442) was 42.3 months (95% CI, 36.0–NE) compared with 35.3 months (95% CI, 30.4-46.4) with BSC (n = 440) in the all-randomized patients with stage II to IIIA disease (HR, 0.79; 95% CI, 0.64-0.96; P = .02).

The median DFS with atezolizumab (n = 507) in the ITT population was not evaluable (95% CI, 36.1–NE) vs 37.2 months (95% CI, 31.6–NE) with BSC (n = 498; HR, 0.81; 95% CI, 0.67-0.99; P = .04). The DFS in this population was not found to cross the significance boundary at the time of the interim DFS analysis.

The HR for OS was 0.77 (95% CI, 0.51-1.17) at the time of the interim analysis, in patients with stage II to IIIA disease and a PD-L1 expression of 1% or higher; the HRs in the all-randomized population with stage II to IIIA disease and the ITT population were 0.99 (95% CI, 0.72-1.33) and 1.07 (95% CI, 0.80-1.42), respectively.

Regarding safety, the most common toxicities experienced by those who received the immunotherapy included increased aspartate aminotransferase, blood creatinine, and alanine aminotransferase. Patients also reported hyperkalemia, rash, cough, hypothyroidism, pyrexia, fatigue/asthenia, musculoskeletal pain, peripheral neuropathy, arthralgia, and pruritus.

References

1. Roche’s VENTANA PD-L1 (SP263) assay receives FDA approval as a companion diagnostic to identify certain non-small cell lung cancer patients eligible for Tecentriq (atezolizumab). News release. Roche. October 22, 2021. Accessed October 22, 2021. https://bit.ly/3C8sv5o
2. FDA approves atezolizumab as adjuvant treatment for non-small cell lung cancer. News release. October 15, 2021. Accessed October 22, 2021. https://bit.ly/3lHUgvQ
3. 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
4. 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