Atezolizumab plus Chemotherapy New First-Line Regimen for Small-Cell Lung Cancer

TOP - February 2019, Vol 12, No 1 - Lung Cancer
Toronto, Canada—Although many new treatments, including targeted therapies and immunotherapies, have recently become available for patients with non–small-cell lung cancer, those with small-cell lung cancer have not seen new treatment options in the past 2 decades. But this is about to change.

First, in August 2018, the FDA approved the immunotherapy nivolumab (Opdivo) for patients with metastatic small-cell lung cancer.

Then, results of a new study showed that atezolizumab (Tecentriq) combined with carboplatin (Paraplatin) plus etoposide (Etopophos) may be a new standard of care for the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC).

The results of the phase 3 IMpower133 clinical trial were presented at the 2018 International Association for the Study of Lung Cancer World Conference on Lung Cancer.

Atezolizumab plus carboplatin and etoposide improved overall survival (OS) and progression-free survival (PFS). At a median follow-up of 13.9 months, the median OS was 12.3 months in the atezolizumab group versus 10.3 months for the placebo arm, which is a 30% reduction in the likelihood of death (P = .007). The median PFS was 5.2 months in the atezolizumab group and 4.3 months in the placebo group (P = .02).

“IMpower133 is the first trial in more than 20 years to show a clinically meaningful improvement in overall survival compared with the current standard of care in first-line ES-SCLC,” stated the senior investigator of this study, Stephen V. Liu, MD, Assistant Professor, Division of Hematology and Oncology, Georgetown University, Washington, DC.

“These findings suggest that atezoliz­umab plus carboplatin and etoposide represents a new first-line treatment for ES-SCLC,” he added.

Clinical Benefit versus Financial Toxicity

Conference Co-President Natasha B. Leighl, MD, MSc, FRCPC, Lung Site Group, Princess Margaret Cancer Centre, Toronto, Canada, acknowledged that an improvement in survival in ES-SCLC is an achievement, but she was more cautious about whether this approach would be widely adopt­ed, mainly because of a modest 2-month gain in survival weighed against the considerable cost of treatment with immunotherapy.

“Is the benefit of atezolizumab during induction or in maintenance? Is a 2-month gain in survival clinically significant? We could say that immunotherapy has lots of financial toxicity, maybe grade 3 or 4. So is this small clinical benefit worth the cost of treatment?” she asked listeners.

“The economic hurdle will depend on regulators. But this is the first positive randomized controlled trial in SCLC, with a 30% survival improvement,” Dr Leighl said. “We still need new treatments for ES-SCLC.”

Phase 3 IMpower133 Study

The randomized, placebo-controlled, double-blind phase 3 IM­power133 study enrolled 403 patients with untreated, measurable ES-SCLC at 106 sites in 21 countries.

The study participants were randomized 1:1 to receive 4 cycles of carboplatin plus etoposide with either 1200 mg of atezolizumab on day 1 of each cycle or placebo, followed by maintenance therapy with atezolizumab or placebo according to previous randomization until disease progression or toxicity. The continuation of treatment was allowed after progression if there was evidence of clinical benefit. Tissue samples were requested, but not mandated, for all patients.

“Atezolizumab did not interfere with the ability to give 4 cycles of standard chemotherapy,” Dr Liu said.

Atezolizumab had a consistent benefit over placebo in all subgroups, including sex, age (aged <65 years), Eastern Cooperative Oncology Group score (0 vs 1), the presence of liver metastases, and the level of tumor mutational burden.

Although the objective response rates were similar in the 2 arms (>60%), approximately 3 times as many patients in the atezolizumab arm had an ongoing response (ie, approximately 15% vs 4% for placebo). The tumor mutational burden correlated with the response to atezolizumab.

The safety profile of the combination of all 3 drugs was similar to what was previously reported with each of the drugs individually, and there were no new safety findings. The frequency of adverse events, including hematologic events, was similar in both arms, except that immune-related adverse events were more common in patients who received atezolizumab (39.9% vs 24.5% for placebo).

Related Items
Antibody–Drug Conjugate Shows Promising Activity in Patients with Advanced or Metastatic EGFR Mutation–Positive NSCLC
Patricia Stewart
TOP - January 2022 Vol 15, No 1 – Online Only published on January 20, 2022 in Lung Cancer
Amivantamab plus Lazertinib Combo Improves Response in Osimertinib-Resistant EGFR-Positive NSCLC
Patricia Stewart
TOP - November 2021 Vol 14, No 7 published on November 10, 2021 in Lung Cancer
Sotorasib Shows Encouraging Activity in Patients with NSCLC and KRAS p.G12C Mutation
Patricia Stewart
TOP - September 2021 Vol 14, No 5 published on September 7, 2021 in Lung Cancer
Neoadjuvant Nivolumab plus Chemotherapy Significantly Improves Pathologic Complete Response in Patients with Resectable NSCLC
Patricia Stewart
TOP - September 2021 Vol 14, No 5 published on September 7, 2021 in Lung Cancer
Educating NSCLC Patients on Adverse Event Management
Kammi Fox-Kay, MSN, RN, AOCNS, ONN-CG(T), Cathy Simmons, RN, BSN, ONN-CG(T), Lauren Welch, MSN, NP-C, AOCNP
Videos published on July 8, 2021 in Interview with the Innovators, Lung Cancer, Adverse Events
Addressing Lung Cancer Screening Disparities in LGBT Populations
William Ackerman
TOP - May 2021 Vol 14, No 3 published on May 14, 2021 in Lung Cancer
Analysis Identifies EGFR as Most Common Mutation in Women with Lung Cancer and No Smoking History
William Ackerman
TOP - May 2021 Vol 14, No 3 published on May 14, 2021 in Lung Cancer
Cemiplimab Potential New Treatment Option for Patients with Advanced NSCLC and PD-L1 ≥50%
Patricia Stewart
TOP - January 2021 Vol 14, No 1 published on February 9, 2021 in Lung Cancer
“Astonishing Results” Seen with First-Line Lorlatinib for the Treatment of ALK-Positive NSCLC
Patricia Stewart
TOP - January 2021 Vol 14, No 1 published on February 9, 2021 in Lung Cancer
Patients with BRAF V600E–Mutant NSCLC Show Improved Overall Survival with Dabrafenib + Trametinib Combination
2020 Year in Review - Non–Small-Cell Lung Cancer published on January 29, 2021 in Lung Cancer
Last modified: July 22, 2021