Irinotecan plus cisplatin (IP) remains the gold standard for Japanese patients with extensive small-cell lung cancer (SCLC), say researchers, after amrubicin plus cisplatin (AP) failed to improve survival in their randomised phase III trial.
The Japanese team, led by Miyako Satouchi, from Hyogo Cancer Center in Akashi, hypothesised that the topoisomerase II inhibitor amrubicin would have equivalent efficacy and less toxicity than the topoisomerase I inhibitor irinotecan.
However, the trial was recommended for early publication at the second interim analysis when the point estimate of the hazard ratio (HR) for overall survival for IP versus AP was 1.41, exceeding the prespecified noninferiority margin of 1.31.
At the last analysis in May 2012, AP was confirmed as inferior to IP treatment, with overall survival of 15.0 months versus 17.7 months, respectively,, and a HR for IP versus AP of 1.43.
Progression-free survival was also significantly longer for IP-treated patients, at a median of 5.6 months versus 5.1 months for those given AP (HR=1.42). The response rate did not significantly differ between the groups.
Patients given IP had significantly less toxicity than those given AP, with grade 4 neutropenia reported in 22.5% versus 79.3% and grade 3 or 4 febrile neutropenia in 10.6% versus 32.1%.
Myelosuppression was improved by an amrubicin dose reduction but remained “relatively serious” and while grade 3 or 4 diarrhoea was more common in IP than AP patients, the researchers believe this may be due tochanges in support therapy for AP.
Moreover, Satouchi et al note that median survival time, indicating postprogression survival, was longer in the IP than AP arm, possibly due to significantly greater use of post-study single-agent use of amrubicinamong patients originally given IP than among AP arm patients.
They suggest that amrubicin may be effective for patients who have failed to respond to IP because of the differing mechanisms of action for the two agents.
“In this phase III trial, AP proved to be inferior to IP, but the results seen here do not negate the activity of this agent in SCLC and perhaps underscore the particular value of amrubicin as second- or third-line therapy in this setting,” the team writes.
Nevertheless, the researchers conclude that they are “unable to recommend AP as standard first-line therapy for [extensive disease]-SCLC”, leaving IP as the first choice in this population.
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