TORONTO – Adding the humanized monoclonal programmed death-ligand 1 (PD-L1) antibody atezolizumab to standard first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall and progression-free survival in the phase 1/3 IMpower133 trial.
Sharon Worcester/MDedge News
Dr. Stephen V. Liu
The combination may represent a new standard-of-care regimen for patients with untreated ES-SCLC, which is highly lethal – with 5-year survival of about 1%-3% – and represents about 13% of all lung cancers, Stephen V. Liu, MD, reported at the World Conference on Lung Cancer.
The findings were published simultaneously in the New England Journal of Medicine.
The median overall survival in 201 patients randomized to receive atezolizumab in addition to carboplatin and etoposide was 12.3 months, compared with 10.3 months in 202 patients who received placebo plus carboplatin and etoposide (hazard ratio, 0.7), Dr. Liu of Georgetown University, Washington, and a member of the trial steering committee said at the meeting, sponsored by the International Association for the Study of Lung Cancer.
“That translates to a 30% reduction in the risk of patient death,” he said at a press briefing during the conference. “Patients receiving atezolizumab had a much greater likelihood of being alive at 1 year, with a 1-year survival rate of 51.7% versus 38.2%.”
Median progression-free survival(PFS) also improved with atezolizumab (5.2 months vs. 4.3 months with placebo; HR, 0.77), as did 6-month PFS. At 12 months there was more than a doubling of PFS in the atezolizumab group (5.0% vs. 12.6%), he said.
Participants in the double-blind trial were treatment-naive all-comers with measurable ES-SCLC and good performance status. They received four 21-day cycles of intravenous carboplatin (area under the curve, 5 mg/mL per minute) on day 1 plus intravenous etoposide (100 mg/m2) on days 1-3 with either concurrent 1,200 mg of atezolizumab on day 1 or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or disease progression.
The treatment benefits were seen across many patient subgroups and regardless of tumor mutational burden.
The atezolizumab safety profile was as expected with no new safety signals and did not compromise patients’ ability to complete four treatment cycles, Dr. Liu noted.
The findings are exciting in that they represent the first in decades to show a significant improvement in survival in patients with ES-SCLC, he said. Although most patients have an initial response to standard-of-care chemotherapy, that response isn’t durable. “As much as we expect a response, we also know that it’s transient; we expect a response, we expect relapse. There hasn’t been a change really in the past 20 years, at least, with this regimen that we’ve been using since the 1980s.”
That’s not for lack of trying, he added, noting that more than 40 phase 3 studies have looked at more than 60 different drugs since the 1970s and have “failed to move the needle.”
Immunotherapy, however, has dramatically improved the therapeutic landscape in non–small cell lung cancer, and preclinical data and clinical experience suggest “a possible synergy between checkpoint inhibition and chemotherapy,” which led to this global study, he explained.
“This is the first study in over 20 years to show a significant improvement in survival and progression-free survival in initial treatment of small cell lung cancer. The concurrent administration of atezolizumab with chemotherapy helped people live longer, compared to chemotherapy alone,” Dr. Liu concluded, adding in a press statement that “this is an exciting time in oncology, and we are thrilled to finally see real progress in the SCLC space.”
When questioned about the role of PD-L1 in this population and the possibility of identifying a subgroup in which this treatment may be more cost effective, he noted that tissue samples weren’t required at enrollment in this study, but were collected from some patients, and future analyses will assess those samples to try to determine if there are subsets of patients who derive particular benefit from immunotherapy in this setting.
“But today, in an all-comer population, this combination has improved survival,” he said.
IMpower133 was sponsored by F. Hoffman–La Roche. Dr. Liu is a speaker or advisory board member for Genentech, Pfizer, Takeda, Celgene, Eli Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, and Ignyta, and has received research or grant support from Genentech, Pfizer, Threshold Pharmaceuticals, Clovis Oncology, Corvus Pharmaceuticals, Esanex, Bayer, OncoMed Pharmaceuticals, Ignyta, Merck, Lycera, AstraZeneca, and Molecular Partners.
SOURCE: Liu SV et al. WCLC 2018, Abstract PL02.07.