COPENHAGEN, Denmark — Atezolizumab significantly extended OS compared with docetaxel in patients receiving second-line or third-line treatment for non–small cell lung cancer, according to results of the primary analysis of the phase 3 OAK study presented at the European Society for Medical Oncology Congress.
Patients benefited from treatment with atezolizumab (Tecentriq, Genentech) regardless of their PD-L1 expression and disease histology.
“The phase 3 OAK study is the first study assessing a PD-L1 antibody in NSCLC, and this is also the largest phase 3 trial in the second line looking at the assessment of checkpoint inhibitors,” Fabrice Barlesi, MD, PhD, head of multidisciplinary oncology and therapeutic innovations department at Aix-Marseille University and Assistance Publique Hôpitaux de Marseille in France, said during a press conference.
The analysis included data from 1,225 patients stratified by PD-L1 status, number of prior chemotherapy regimens (1 vs. 2) and histology. Fifty-five percent of patients met the criteria for PD-L1 positivity, or at least 1% of PD-L1 expression in tumor cells (TC) or tumor-infiltrating immune cells (IC).
Researchers randomly assigned patients 1:1 to receive 1,200 mg IV atezolizumab every 3 weeks or 75 mg/m2 IV docetaxel every 3 weeks.
OS in the intent-to-treat population, as well as in PD-L1–expressing patients, served as the co-primary endpoints. Secondary endpoints included PFS, overall response rate, duration of response and safety.
Researchers conducted the primary efficacy analysis in the first 850 patients (median age, 64 years; 61% men) enrolled. Twenty-five percent of patients had received two prior lines of therapy, 26% had squamous histology, 67% were past smokers and 37% had a performance status of 0.
In the intent-to-treat population, median OS was 13.8 months with atezolizumab compared with 9.6 months with docetaxel (HR = 0.73; 95% CI, 0.62-0.87).
“The curves separated early and remained separated over time,” Barlesi said. “There also was a clinically meaningful improvement in median OS of 4 months for patients receiving the PD-L1 inhibitor.”
Atezolizumab improved OS regardless of PD-L1 expression levels. Patients with any level of expression, or TC 1/2/3 or IC 1/2/3, achieved a median OS of 15.7 months with atezolizumab compared with 10.3 months with docetaxel (HR = 0.74; 95% CI, 0.58-0.93).
The HRs ranged from 0.75 (95% CI, 0.59-0.96) among patients with TC 0 and IC 0 — or no PD-L1 expression — to 0.41 (95% CI, 0.27-0.64) in patients with TC 3 or IC 3, the highest level of expression.
Atezolizumab also conferred longer survival in patients with squamous histology (8.9 months vs. 7.7 months; HR = 0.73; 95% CI, 0.54-0.98) and nonsquamous histology (15.6 months vs. 11.2 months; HR = 0.73; 95% CI, 0,6-0.89).
The ORR was 13.6% with atezolizumab and 13.4% with docetaxel. Median PFS was 2.8 months with atezolizumab and 4 months with docetaxel.
Median duration of treatment was longer with atezolizumab (16.3 months vs. 6.2 months).
Still, fewer patients treated with atezolizumab experienced a treatment-related grade 3 or grade 4 adverse event (15% vs. 43%), treatment-related grade 5 adverse event (0% vs. 0.2%), or an adverse event that led to treatment withdrawal (8% vs. 19%) or dose modification or delay (25% vs. 36%).
“The goal of treatment is to allow the immune system to control and possibly eliminate cancer cells, so atezolizumab might be useful in a very large setting of different cancers,” Barlesi said in a press release. – by Alexandra Todak
Barlesi F, et al. Abstract LBA44_PR. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.
Disclosure: F. Hoffmann-La Roche funded this study. Barlesi reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.