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Atezolizumab extends OS for PD-L1-selected patients with non-small cell lung cancer
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BARCELONA, Spain — Atezolizumab significantly prolonged OS compared with platinum-based chemotherapy for patients with newly diagnosed non-small cell lung cancer whose tumors expressed high levels of PD-L1, according to an interim survival analysis from the phase 3 IMpower110 study presented at European Society for Medical Oncology Congress.
Safety outcomes also favored atezolizumab (Tecentriq, Genentech).
“Atezolizumab represents a promising first-line treatment option [for this patient population],” David R. Spigel, MD, chief scientific officer and lung cancer program director at Sarah Cannon Research Institute, said during his presentation.
Checkpoint inhibitors that target PD-1/PD-L1 — either alone or in combination with platinum-based doublet chemotherapy — can be used as first-line therapy for patients with metastatic NSCLC. PD-L1 expression typically informs the selection of the most appropriate agents.
Monotherapy with checkpoint inhibitors remains a viable treatment approach for patients who are not eligible for combination therapy, according to study background.
Spigel and colleagues conducted IMpower110 to evaluate atezolizumab — a monoclonal antibody designed to bind with PD-L1 — as first-line monotherapy for PD-L1-selected patients independent of tumor histology.
The trial included 572 chemotherapy-naive patients with stage IV nonsquamous or squamous NSCLC. All patients had PD-L1 expression of at least 1% on tumor cells (TC) or tumor-infiltrating immune cells (IC); measurable disease; and ECOG performance status of 0 or 1. No patients included in this analysis had ALK or EGFR mutations.
Researchers randomly assigned half of the patients to 1,200 mg IV atezolizumab every 3 weeks. Treatment continued until progressive disease or loss of clinical benefit.
The other half received platinum-based chemotherapy administered in four or six 21-day cycles. Patients with nonsquamous histology received cisplatin 75 mg/m2, or carboplatin area under the curve 6 plus pemetrexed 500 mg/m2 via IV every 3 weeks. Patients with squamous histology received cisplatin 75 mg/m2 plus gemcitabine 1,250 mg/m2, or carboplatin area under the curve 5 plus gemcitabine 1,000 mg/m2 via IV every 3 weeks.
Chemotherapy continued until progressive disease.
Investigators stratified patients by sex, ECOG performance status, histology and tumor PD-L1 status.
OS tested hierarchically served as the primary endpoint.
The primary efficacy populations included 554 patients classified as TC1/2/3 or IC1/2/3 (PD-L1 expression of 1% or greater by TC or IC); 328 patients classified as TC2/3 or IC2/3 (PD-L1 expression of 5% or greater by TC or IC); and 205 patients classified as TC3 or IC3 (PD-L1 expression of 50% or greater by TC, or 10% or greater by IC).
Median follow-up was 15.7 months.
Results showed atezolizumab significantly improved median OS in the TC3 or IC3 group (20.2 months vs. 13.1 months; HR = 0.59; 95% CI, 0.4-0.89). This benefit persisted in all key subgroups.
Atezolizumab conferred an OS benefit in the TC2/3 or IC2/3 group (18.2 months vs. 14.9 months; HR = 0.72; 95% CI, 0.52-0.99), but it did not cross the prespecified testing boundary. Consequently, the TC1/2/3 or IC1/2/3 group was not formally tested.
A higher percentage of patients assigned chemotherapy received subsequent cancer therapies (49.5% vs. 29.6%).
Atezolizumab’s safety profile appeared consistent with prior observations, and no new safety signals were identified.
The safety analysis included 286 patients assigned atezolizumab and 263 patients assigned chemotherapy. Patients assigned chemotherapy were more likely to experience any treatment-related adverse events (85.2% vs. 60.5%), grade 3/grade 4 treatment-related adverse events (44.1% vs. 12.9%), grade 5 treatment-related serious adverse events (0.4% vs. 0%), and adverse events that led to treatment withdrawal (16.3% vs. 6.3%).
“IMpower110 will continue to the OS final analysis,” Spigel said. “Importantly, additional biomarker analyses will be presented at a future congress, including ongoing work with other assays to measure PD-1 expression ... as well as tumor mutation burden data.”– by Mark Leiser
Reference: Spigel D, et al. Abstract LBA78. Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct. 1, 2019; Barcelona, Spain.
Disclosures: F. Hoffmann-La Roche funded this study. Spigel reports research funding to his institution from, consultant/advisory roles with payments to his institution from, or travel, accommodations or expenses from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech/Roche, Novartis, Pfizer, Takeda and several other pharmaceutical companies. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Naiyer A. Rizvi, MD, PhD
It’s definitely gratifying to see these data be so clearly positive.
TC3/IC3 really is a distinct population in NSCLC. About 9% of patients have TC3 and 6% have IC3, with only a 1% overlap. In this patient population from IMpower110, we see a very strong HR and a very clear separation of curves with durable benefit with atezolizumab treatment. PFS similarly has a very clear separation of the curves.
The TC2/IC2 group represents are larger proportion of patients, with about 13% having that level of tumor cell expression, 13% having that level of immune cell expression, and about a 10% overlap. With that lower threshold, again we see a very nice HR and an OS of 14.9 months, suggesting some clear benefit for this patient population, as well.
I think atezolizumab for IC3/TC3 patients is a new standard of care for first-line NSCLC, in addition to pembrolizumab (Keytruda, Merck). I think there are some questions that probably will be answered at future congresses. These include what the results look like with the 22C3 assay. I’m also really interested what the TC3 and IC3 populations look like separately. Some previously published data of trials from the second-line setting show the IC3 group may have lower response and shorter PFS than the TC3 patients. Is this really a distinct population? Is this a population that is separate from what we identify with the 22C3 assay, so there could be an additional 6% or 7% of patients who are amenable to first-line therapy with atezolizumab? That will be an interesting question to look at.
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