Atezolizumab Appears Effective for Patients with NSCLC with High PD-L1 Expression

Atezolizumab (Tecentriq) treatment resulted in significantly longer overall survival (OS) compared with platinum-based chemotherapy among patients with non-small cell lung cancer (NSCLC) with high PD-L1 expression, regardless of histologic type, according to results from a phase 3 trial published in the New England Journal of Medicine.¹

The findings from this global, open-label, randomized trial supported the FDA approval of atezolizumab for this indication in May.

“These are exciting results that could be life-changing for many patients,” lead author Roy S. Herbst, MD, PhD, chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, as well as associate cancer center director for Translational Research at Yale Cancer Center, said in a press release.² “Lung cancer is the most common cancer worldwide, with more than 1.5 million patients diagnosed each year. Half of patients are diagnosed with metastatic disease and they could be a candidate for this drug.”

The study enrolled patients with metastatic nonsquamous or squamous NSCLC who had not previously received chemotherapy and who had PD-L1 expression on at least 1% of tumor cells or at least 1% of tumor-infiltrating immune cells as assessed by the SP142 immunohistochemical assay. Patients were randomized 1:1 to receive either atezolizumab or chemotherapy.

The primary end point for the study was OS tested hierarchically according to PD-L1 expression status among patients in the intention-to-treat population whose tumors were wild-type with regard to EGFR mutations or ALK translocations. Key secondary end points included investigator assessed progression-free survival (PFS) according to RECIST, version 1.1, the occurrence and duration of a response, as well as overall and investigator assessed PFS according to RECIST, version 1.1, in prespecified subgroups with regard to PD-L1 expression and blood-based tumor mutational burden.

In total, 572 patients were enrolled, with 285 patients assigned to receive atezolizumab and 287 assigned to receive chemotherapy. The population with EGFR and ALK wild-type tumors consisted of 554 patients, with 277 patients randomized to each group. Of note, 18 patients with an EGFR mutation or ALK translocation were enrolled and were excluded from the primary analysis population but were included in the safety population.

As of the data cutoff date of September 10, 2018, the median follow-up times for survival among patients with EGFR and ALK wild-type tumors who had high PD-L1 expression, high or intermediate PD-L1 expression, and any PD-L1 expression were 15.7 months (range, 0-35), 15.2 months (range, 0-35), and 13.4 months (range, 0-35), respectively.

The median treatment duration for atezolizumab was 5.3 months. In the chemotherapy group, the median treatment duration was 2.1 months for cisplatin, 2.3 months for carboplatin, 2.6 months for gemcitabine, and 3.5 months for pemetrexed.

In the subgroup of 205 patients with EGFR and ALK wild-type tumors who had the highest expression of PD-L1, the median OS was longer by 7.1 months in the atezolizumab group than in the chemotherapy group (20.2 months vs. 13.1 months; HR, 0.59; P = .01). However, as of the data cutoff, 146 of these patients (71.2%) with EGFR and ALK wild-type tumors who had high PD-L1 expression had had disease progression or had died. PFS was 8.1 months in the atezolizumab group and 5.0 months in the chemotherapy group (HR, 0.63; 95% CI, 0.45-0.88).

Ultimately, OS and PFS favored atezolizumab in the subgroups with a high blood-based tumor mutational burden.

“Among patients with EGFR and ALK wild-type tumors who received atezolizumab, observed results for overall survival according to level of PD-L1 expression were similar to those seen in the phase 3 KEYNOTE-042 trial comparing pembrolizumab with chemotherapy; in both trials, the patients with high PD-L1 expression had the most benefit,” the study authors noted.

Among all patients who could be evaluated for safety, adverse events (AEs) occurred in 90.2% of the patients in the atezolizumab group and in 94.7% of those in the chemotherapy group. Moreover, grade 3 or 4 AEs occurred in 30.1% and 52.5% of the patients in the respective groups, with the most common (≥5% in either group) being anemia, neutropenia, and thrombocytopenia (all with chemotherapy).

“Also encouraging is that atezolizumab was generally well tolerated,” Herbst said. “Side effects for patients were similar to those seen in other trials of the drug, which has been approved for treatments of several types of cancer.”

Ongoing clinical studies are now analyzing combinations of atezolizumab with other drugs to treat patients with NSCLC. Additionally, the ongoing randomized, phase 3 Blood-First Assay Screening Trial (BFAST; NCT03178552) is prospectively evaluating first-line treatment with atezolizumab monotherapy as compared with platinum-based chemotherapy in patients with advanced or metastatic NSCLC who have a positive blood-based tumor mutational burden score.

References:

1. Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC. New England Journal of Medicine. doi: 10.1056/NEJMoa1917346

2. Yale Trial Validates Immunotherapy Treatment for Non-Small Cell Lung Cancer [news release]. Yale Cancer Center. Published September 30, 2020. Accessed October 1, 2020. https://www.yalecancercenter.org/news-article/27677/