Atezolizumab-bevacizumab confers ‘much higher than usual’ survival rates in NSCLC subset

ByJennifer R. Southall

Fact checked byMindy Valcarcel, MS

The addition of atezolizumab to bevacizumab showed promising efficacy among patients with nonsquamous non-small cell lung cancer with high tumor mutational burden, according to results of a phase 2 trial published in JAMA Oncology.

In addition, the combination of the anti-PD-L1 monoclonal antibody atezolizumab (Tecentriq, Genentech), plus the VEGF inhibitor bevacizumab (Avastin, Genentech) appeared safe, findings showed.

Results of the nonrandomized phase 2 TELMA trial — Data derived from Provencio M, et al. *JAMA Oncol.* 2022;doi:10.1001/jamaoncol.2022.5959.

Background and methods

“We are trying to improve the way we select our patients for immunotherapy, beyond PD-L1 expression status, because even with high PD-L1 expression, patients may experience disease progression,” Mariano Provencio, MD, PhD, researcher in the department of medical oncology at Hospital Universitario Puerta de Hierro-Majadahonda in Madrid, told Healio.

Provencio and colleagues assessed the clinical benefits and safety of atezolizumab plus bevacizumab among patients with advanced NSCLC with high mutational burden who received care across 13 sites in Spain between May 2019 and January 2021.

Mariano Provencio

The multicenter, single-arm, open-label, phase 2 TELMA study included 38 patients (mean age, 63.7 years; 73.7% men; 100% white) assigned 1,200 mg atezolizumab plus 15 mg/kg bevacizumab on day 1 of each 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, patient withdrawal, investigator-decision or death.

One-year PFS, defined as time from enrollment to disease progression or death, served as the primary endpoint. Researchers monitored adverse events according to the NCI Common Terminology Criteria for Adverse Events, version 4.0.

Findings

Results showed a 1-year PFS rate of 51.3% (95% CI, 34.2-66) and a 1-year OS rate of 72% (95% CI, 54.1-83.9) with the combination regimen.

Researchers observed median PFS of 13 months (95% CI, 7.9-18) and median OS was not reached.

In addition, 42.1% of patients achieved an objective response and 78.9% achieved disease control. Researchers observed a median time to treatment response of 2.8 months (interquartile range, 2.8 -3.58) and a median duration of response of 11.7 months, with half of responses ongoing at the time of data cutoff.

Common — mostly grade 1 to grade 2 — adverse events with atezolizumab included fatigue (15.8%) and pruritus (15.8%), compared with hypertension (26.3%) and proteinuria (10.5%) with bevacizumab. Two patients discontinued atezolizumab and three patients discontinued bevacizumab.

Of note, researchers did not observe an association between PD-L1 and treatment response, PFS or OS.

Limitations of the study included its single-arm design, limited patient cohort size and incomplete follow-up period for long-term survival analysis, as well as the decreased number of blood samples available for exploratory analysis, according to the researchers.

Implications

“With intermediate-to-high tumor mutation burden, regardless of PD-L1 expression, and with the addition of an antiangiogenic, we obtained a PFS of 13 months, which is much higher than usual in these cases, as is the OS rate,” Provencio said. “New evidence is developing for antiangiogenic drugs with mono-immunotherapy. We will continue to explore this combination in the early stages.”

The trial did not answer the question of whether bevacizumab added to atezolizumab improves outcomes vs. atezolizumab alone in this patient population, according to an accompanying editorial by Biagio Ricciuti, MD, research fellow in the department of medicine, and Mark M. Awad, MD, PhD, associate professor in the department of medicine, both at Harvard Medical School.

“Therefore, in absence of prospective, randomized clinical studies comparing these treatment strategies, the TELMA regimen should not yet be incorporated into clinical practice for the initial treatment of advanced NSCLC, particularly given the added toxic effects associated with bevacizumab,” they wrote. “Hopefully, future optimization and integration of [tumor mutational burden], PD-L1 and other molecular and immunophenotypic biomarkers will inform rational treatment selection to improve outcomes for patients with advanced NSCLC.”

References :

For more information:

Mariano Provencio, MD, PhD, can be reached at mprovenciop@gmail.com.

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Sources/Disclosures

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Source:

Provencio M, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2022.5959.

Disclosures: Provencio reports grants from Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche and Takeda outside the submitted work; consultant/advisory roles with AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Roche and Takeda; serving on speakers bureaus for AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme and Roche; research funding from Boehringer Ingelheim, Bristol Myers Squibb, Pierre Fabre and Roche; and travel/accommodations/expenses from AstraZeneca, Bristol Myers Squibb and Roche. Please see the study for all other authors’ relevant financial disclosures. Ricciuti reports consultant fees from Regeneron outside the submitted work. Awad reports receiving grants from Amgen, AstraZeneca, Bristol Myers Squibb, Genentech and Eli Lilly; and personal fees outside the submitted work from Ariad, AstraZeneca, Blueprint Medicine, Bristol Myers Squibb, EMD Serono, Genentech, Gritstone bio, Iovance Therapeutics, Maverick Therapeutics, Merck, Mirarti Therapeutics, Nektar, NextCure, Novartis, NovaRx and Syndax.

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