Dose-Dense Paclitaxel Fails To Boost Ovarian Cancer PFS

Weekly and 3-weekly regimens of paclitaxel offer comparable progression-free survival for ovarian cancer patients

medwireNews: A dose-dense weekly paclitaxel regimen does not improve progression-free survival (PFS) for patients with ovarian cancer compared with a standard 3-weekly schedule, suggest phase III trial findings.

The study initially included patients with newly diagnosed, untreated or incompletely resected stage III or any stage IV epithelial ovarian, fallopian tube or primary peritoneal cancer. The criteria were later expanded to include patients with stage II or III disease with no residual lesions greater than 1 cm, the researchers report in The New England Journal of Medicine.

Intention-to-treat analysis gave a median PFS of 14.7 months for the 346 patients given paclitaxel at a dose of 80 mg/m2 every week plus carboplatin to an area under the curve of 6 for six cycles, and a comparable median PFS of 14.0 months for the 346 given six cycles of paclitaxel 175 mg/m2 every 3 weeks plus carboplatin.

The majority (84%) of patients also opted to receive the vascular endothelial growth factor inhibitor bevacizumab 15 mg/kg every 21 days from the second cycle of treatment, explain John Chan, from California Pacific–Palo Alto Medical Foundation, Sutter Cancer Institute in San Francisco, USA, and fellow Gynecologic Oncology Group–0252 trial investigators.

Among the patients given bevacizumab, median PFS did not significantly differ between the weekly and 3-weekly paclitaxel patient groups (14.9 vs 14.7 months), although patients who did not use bevacizumab had significantly better PFS when given the weekly regimen (14.2 vs 10.3 months, hazard ratio=0.62).

Further analysis confirmed there was a significant difference between the treatment groups in the presence and absence of bevacizumab, prompting the authors to suggest that “it is possible that the overall difference was dominated by the addition of bevacizumab to the study treatment”.

But they admit that “we cannot dismiss the fact that this difference could be due to an imbalance of unknown prognostic factors”.

John Chan and team also note that economic considerations are required for comparative effectiveness studies.

“Although paclitaxel and carboplatin administered every 3 weeks and combined with bevacizumab may be more convenient than weekly paclitaxel and carboplatin without bevacizumab, the every-3-week regimen is also associated with higher costs, with an incremental cost-effectiveness ratio as calculated by others of [US]$401,088 versus $5,809 per progression-free life–year saved”, they write.

Safety analysis of 343 patients given weekly paclitaxel and 340 patients given the 3-weekly regimen showed that grade 3 or more severe anaemia was significantly more common in the dose-dense group, affecting 36% versus 16%, whereas neutropenia of at least grade 3 was significantly less common, affecting 72% versus 83%.

The endpoint of grade 2 or more severe sensory neuropathy, but not grade 3 or higher symptoms, was also significantly more common with weekly than 3-weekly paclitaxel (26 vs 18%).

The researchers did not identify any toxicity specifically associated with combined paclitaxel plus bevacizumab.

Reference

Chan JK, Brady MF, Penson RT,et al. Weekly vs. Every-3-week paclitaxel and carboplatin for ovarian cancer. N Engl J Med 2016; 374: 738–748. DOI: 10.1056/NEJMoa1505067

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