In a phase 3 trial, carboplatin plus etoposide significantly prolonged progression-free survival (PFS), when compared with topotecan, in patients with advanced or relapsed, sensitive SCLC.
All patients had responded to first-line platinum plus etoposide, but they experienced relapse or progression 90 days or more after completing that treatment, according to study author Nathalie Baize, MD, of Angers University Hospital in France, and colleagues.
For this trial, Dr. Baize and colleagues enrolled 164 patients with advanced or relapsed SCLC. The median age of the 162 evaluable patients was 64 years, about two-thirds were men, and about 60% had an Eastern Cooperative Oncology Group performance status of 1.
The patients were randomized 1:1 to intravenous carboplatin (area under the curve 5 mg/mL per min on day 1) plus intravenous etoposide (100 mg/m² from day 1 to day 3) or to oral topotecan (2.3 mg/m² from day 1 to day 5 for six cycles). Primary prophylactic filgrastim was recommended for all patients in both treatment groups.
Results: Survival and adverse events
The median follow-up was 22.7 months. The median PFS was significantly longer in the combination therapy arm, at 4.7 months versus 2.7 months in the topotecan arm (stratified hazard ratio 0.57, P = .0041).
The median overall survival was similar in both arms, at 7.5 months in the carboplatin-etoposide arm and 7.4 months in the topotecan arm.
Patients in the carboplatin-etoposide arm had a significantly higher objective response rate, at 49% versus 25% in the topotecan arm (P = .0024).
The most common grade 3-4 adverse events (in the topotecan and combination arms, respectively) were neutropenia (22% vs. 14%), thrombocytopenia (36% vs. 31%), and anemia (21% vs. 25%).
Serious adverse events with hospitalization were reported in 37% of patients in the carboplatin-etoposide arm 43% in the topotecan arm. Febrile neutropenia with sepsis led to two treatment-related deaths in the topotecan group but none in the carboplatin-etoposide group.
Reasonable option for some
Based on the results of this trial, Dr. Baize and colleagues concluded that carboplatin-etoposide rechallenge “can be considered a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer.”
However, while this trial was enrolling patients, immunotherapy and chemotherapy combinations became the standard of care in SCLC, Oscar Arrieta, MD, of Instituto Nacional de Cancerología in Mexico City, and colleagues noted in a related editorial.
Therefore, “reasonable doubts emerge regarding the application of this strategy in patients receiving immunotherapy,” Dr. Arrieta and colleagues wrote.
The editorialists urged conduct of a randomized trial to evaluate rechallenge with carboplatin plus etoposide versus lurbinectedin, which was approved earlier this year by the Food and Drug Administration for the treatment of sensitive and resistant relapsed SCLC.
Commenting on the choice between a platinum-etoposide combination and lurbinectedin, Sarah Goldberg, MD, of Yale University, New Haven, Conn., noted that she and her colleagues have been using the chemotherapy combination for several years.
“This trial confirms that practice and that it’s still a reasonable option for some patients,” Dr. Goldberg said in an interview.
For patients who had a very good first-line response to platinum-etoposide, longer than 180 days (even longer than the 90-day standard in the current trial), she said, “it seems like a rechallenge with platinum-etoposide would potentially be even more effective, and I’d save lurbinectedin for a later line.
“With refractory disease, less than 90 days, I would consider lurbinectedin,” Dr. Goldberg said.
This study was funded by Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie). The researchers disclosed relationships with Pfizer, Roche, AbbVie, and many other companies. Dr. Arrieta disclosed relationships with AstraZeneca, Boehringer Ingelheim, Roche, Lilly, Merck, Pfizer, and Bristol-Myers Squibb. The other editorialists declared no competing interests. Dr. Goldberg disclosed relationships with AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum, Blueprint Medicine, Sanofi Genzyme, Daiichi Sankyo, and Regeneron.
SOURCE: Baize N et al. Lancet Oncol. 2020;21:1224-33.