Longer Survival Observed With Atezolizumab for High PD-L1 NSCLC

In a phase 3 trial, atezolizumab (Tecentriq) demonstrated a significantly longer overall survival (OS) in patients with non-small cell lung cancer (NSCLC) who had high PD-L1 expression regardless of histologic type compared with platinum-based chemotherapy.¹

“These are exciting results that could be life-changing for many patients,” Roy S. Herbst, MD, PhD, the chief of medical oncology at Yale Cancer Center (YCC) and Smilow Cancer Hospital, associate cancer center director for Translational Research at YCC, and lead author of the study, said in a statement. “Lung cancer is the most common cancer worldwide, with more than 1.5 million patients diagnosed each year. Half of patients [with NSCLC] are diagnosed with metastatic disease and could be a candidate for this drug.”²

The randomized, open-label IMpower110 study (NCT02409342) investigated 572 patients with stage IV non-squamous or squamous NSCLC, of which 205 had EGFR and ALK wild-type tumors with the highest expression of PD-L1. This subgroup experienced a median OS of 20.2 months with atezolizumab versus 13.1 months with chemotherapy (HR, 0.59; 95% CI, 0.40-0.89; P =.01).

For patients with high or intermediate PD-L1 expression, the median OS did not cross the prespecified alpha boundary at 18.2 months with immunotherapy versus 14.9 months with chemotherapy (HR, 0.72; 95% CI, 0.52-0.99; P =.04). Because of this, the OS for patients with any PD-L1 expression was not formally tested but came to 17.5 months for those receiving atezolizumab and 14.1 months for this receiving platinum therapy (HR, 0.83; 95% CI, 0.65-1.07).

Of the 205 patients with high PD-L1 status, 146 (71.2%) had progressed or died by the data cutoff. The median progression-free survival (PFS) was 8.1 months and 5.0 months for the atezolizumab arm and chemotherapy arm, respectively (HR,0.63; 95% CI, 0.45-0.88). Those who expressed high or intermediate PD-L1 had a PFS of 7.2 months with atezolizumab and 5.5 months with chemotherapy.

Patients with high blood-based tumor mutational burden (TMB) had OS and PFS that favored atezolizumab over chemotherapy. There were 389 patients who could be evaluated for blood-based TMB and those who had a score of at least 16 exhibited an OS of 13.9 months in the atezolizumab group and 8.5 months in the chemotherapy group (unstratified HR, 0.75; 95% CI, 0.41-1.35).

“Among these patients with NSCLC, those with high TMB who received atezolizumab showed improved PFS of 7 months versus 4 months for those given chemotherapy,” Herbst said in the press release. “This finding suggests that the biomarker should be explored further.”

There was an investigator-assessed confirmed response rate of 38.3% for patients with high PD-L1 expression who were given atezolizumab and 28.6% for those given platinum therapy. These responses were ongoing in 68.3% of patients in the atezolizumab at the time of the data cutoff.

For patients included in the safety population, which was made up of 549 patients with any level of PD-L1 expression or EGFR and ALK alterations, the were adverse events (AEs) observed in 90.2% receiving atezolizumab and 94.7% receiving chemotherapy. The grade 3/4 AEs occurred in 30.1% of patients in the atezolizumab group and 52.5% in the chemotherapy group. The most common grade 3/4 events were anemia, neutropenia, and thrombocytopenia in 5% or more of patients in either group.

There were 11 patients in per group who experienced a grade 5 AE.

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

Patients on this trial were randomized 1:1 to atezolizumab at 1200 mg intravenously or platinum-based chemotherapy at 4 or 6 cycles every 3 weeks. The chemotherapy could be either cisplatin or carboplatin plus pemetrexed (Alimta) or gemcitabine. Crossover was not allowed on this trial and the primary end point was OS in patients with PD-L1 expression and no EGFR mutations or ALK translocations.

_References:

_{1. Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC. N Engl J Med. 2020;383:1328-1339. 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://bit.ly/2HEWQRI}