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First-line atezolizumab improves PFS for advanced squamous non-small cell lung cancer
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CHICAGO — The addition of frontline atezolizumab to chemotherapy prolonged PFS among patients with advanced squamous non-small cell lung cancer, according to findings of the phase 3 IMpower131 study presented at the ASCO Annual Meeting.
“Squamous NSCLC remains a very difficult to treat disease and there have been limited treatment options presented to us over the past few decades,” Robert M. Jotte, MD, PhD, medical director and co-chair of USON Thoracic Committee of Rocky Mountain Cancer Centers, said during a press briefing. “Between 25% and 30% of NSCLCs have tumors that indeed can be classified as squamous cell carcinoma, with 1-year survival rates less than 15% overall and only 2% among those with advanced-stage disease.”
IMpower131 is an open-label, multicenter randomized study of frontline atezolizumab (Tecentriq, Genentech) plus chemotherapy — carboplatin and paclitaxel (arm A, n = 338) or carboplatin and nab-paclitaxel (arm B; n = 343) — compared with chemotherapy (carboplatin and nab-paclitaxel [arm C; n = 340]) alone among 1,021 patients with squamous NSCLC.
Patients assigned atezolizumab received 1,200-mg doses every 3 weeks until loss of clinical benefit; all patients received chemotherapy for four or six cycles.
Jotte presented outcome data for arms B and C; outcomes for arm A were not yet available at the time of the presentation.
Minimum follow-up was 9.8 months and median follow-up was 17.1 months.
Median PFS was 6.3 months in arm B compared with 5.6 months in arm C, equating to a 29% reduction in risk for progression (HR = 0.71; 95% CI, 0.6-0.85), regardless of PD-L1 expression.
PFS increased twofold among those in arm B, 24.7% of whom achieved 1-year PFS compared with 12% of those assigned chemotherapy alone.
Although benefit occurred across PD-L1 expression levels, patients with high PD-L1 expression demonstrated greater PFS benefit (median PFS for arm B vs. C, 10.1 months vs. 5.5 months; HR = 0.44; 95% CI, 0.27-0.71)
Overall response rate was 49% in arm B and 41% in arm C; among those with PD-L1-high tumors, ORR was 60% for arm B and 33% for arm C.
Median duration of response (7.2 months vs. 5.2 months) and the proportion of patients with ongoing responses (32% vs. 16%) also favored the atezolizumab combination.
The rate for grade 3 to grade 4 adverse events — including rash, colitis and low thyroid hormone — was 68% in the combination arm vs. 57% with chemotherapy alone. However, the safety profile of the combination therapy was manageable and consistent with already known safety risks of the individual therapies, Jotte said.
He further noted that a statistically significant OS benefit was not observed (median OS, 14 months for atezolizumab vs. 13.9 months for chemotherapy alone) at the time of this interim analysis. At 24 months, 31.9% of patients in arm B and 24.1% in arm C achieved OS.
“Results of IMpower131 demonstrate that patients with advanced squamous NSCLC benefit more from initial treatment with atezolizumab plus chemotherapy vs. chemotherapy alone,” Jotte said. “In addition, cancer had not worsened in nearly 25% of patients receiving the combination regimen compared with 12% of those receiving chemotherapy alone. OS continues to be followed with the next interim analysis anticipated later this year.” – by Jennifer Southall
Reference:
Jotte RM, et al. LBA9000. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: The study was funded by F. Hoffmann-La Roche Ltd. Jotte reports honoraria and travel accommodations from, as well as a speakers bureau role with, Bristol-Myers Squibb. Please see the abstract for a list of all other authors’ relevant financial disclosures.
Perspective
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Benjamin C. Creelan, MD
What makes this special is that is shows that the extension of concurrent chemotherapy in combination with immunotherapy could be applied to a new NSCLC population — those with squamous cell disease. Thus, the effect seen in KEYNOTE-169 with pemetrexed was not unique to nonsquamous patients and could be extended into the other subgroups of NSCLC and, by default, also can likely be extended into other disease settings for which platinum-based therapy has traditionally been our gold standard. It is looking like platinum plus PD-1 inhibitors, like pembrolizumab, are going to be our new gold standard across a lot of solid tumor diseases where platinum-based therapy has traditionally been the first-line option.
The cons of this study are that the treatment-associated adverse effects are certainly higher with the combination regimen — they were nearly double. The study also raises some important questions such as, which patients will only require monotherapy and are there patients who do not need a doublet?
Overall, the study raises the overall benchmark of our expectations with first-line treatment for squamous NSCLC. It is great to have all these combination therapy trials that are being reported on.
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