Survival Boost With Triple Regimen In Sensitive Relapsed Small-Cell Lung Cancer

Phase III trial results support the use of second-line cisplatin, etoposide plus irinotecan in patients with sensitive relapsed small-cell lung cancer

medwireNews: Second-line treatment with the combination of cisplatin, etoposide and irinotecan significantly improves survival in selected patients with sensitive relapsed small-cell lung cancer, say Japanese researchers who used topotecan monotherapy as the comparator treatment.

They believe that the triple regimen “could be regarded as the standard second-line chemotherapy” for relapsed patients who are in good general physical condition.

But in a commentary accompanying the research in The Lancet Oncology, Gregory Kalemkerian, from the University of Michigan in Ann Arbor, USA, urges caution. “The survival reported in JCOG0605 is encouraging for the highly selected patients enrolled in the trial, but previous experience suggests that promising initial results might not be reproducible in other populations”, he writes.

“Although nobody is happy with the status quo, further study is needed before the cisplatin, etoposide, and irinotecan combination can be accepted as the standard treatment for patients with relapsed small-cell lung cancer.”

The phase III trial enrolled Japanese small-cell cancer patients who experienced relapse or progression no earlier than 90 days after completion of first-line therapy (ie, those with so-called sensitive relapse). Participants were required to be 20–75 years of age and have an ECOG performance status of 0–2.

After a median follow-up of 22.7 months, overall survival (OS) was a median of 18.2 months for the 90 patients given the triple regimen – specifically, cisplatin 25 mg/m2 on days 1 and 8, etoposide 60 mg/m2 on days 1 to 3, and irinotecan 90 mg/m2 on day 8 of a 2-week cycle for up to five cycles. This median OS time was longer than the 12.5 months observed for the 90 participants treated with four cycles of topotecan 1 mg/m2 on days 1 to 5 of a 3-week cycle, and equated to a significant hazard ratio of 0.67.

Patients in the combination therapy arm also had significantly longer median progression-free survival than those in the topotecan alone arm, at 5.7 versus 3.6 months, and a significantly higher proportion achieved an objective response, at 84% versus 27%.

However, the improved outcomes came at the cost of increased toxicity, despite all patients in the combination arm receiving granulocyte colony-stimulating factor. The incidence of grade 3 or 4 anaemia (84 vs 28%), leucopenia (80 vs 51%), thrombocytopenia (41 vs 28%) and febrile neutropenia (31 vs 7%) were higher in the combination than in the monotherapy group. The rate of neutropenia was similar though, at 83% in the combination arm and 86% in topotecan-treated patients.

Half the patients given the combination regimen required a dose reduction and 22% discontinued treatment as a result of toxicity, which the commentator says raises “serious concerns about the tolerability of this regimen”.

Researcher Koichi Goto, from National Cancer Center Hospital East in Kashiwa, Japan, and colleagues acknowledge the severe toxicity, but believe that “the 6-month increased survival relative to topotecan therapy represents a substantial benefit” for this patient population.

The commentator and study authors agree that quality-of-life assessments would have been useful. Gregory Kalemkerian writes: “Relapsed small-cell lung cancer is a terminal disease in which quality of life usually drives survival, so therapy needs to allow patients to continue living their lives without inducing undue toxic effects.”

References

Goto K, Ohe Y, Shibata T, et al. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2016; Advance online publication 13 June. doi: http://dx.doi.org/10.1016/S1470-2045(16)30104-8

Kalemkerian GP. Combination chemotherapy for relapsed small-cell lung cancer. Lancet Oncol 2016; Advance online publication 13 June. doi: http://dx.doi.org/10.1016/S1470-2045(16)30160-7

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