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Wednesday, September 6, 2017

New Data Confirms Standard Dosing of Chemotherapy in Ovarian Cancer Treatment

Women with ovarian cancer can safely stick to the standard 3-week dosing schedule for paclitaxel rather than boosting up to a weekly dose-dense regimen, according to results of the phase III ICON8 trial to be presented at the ESMO 2017 Congress in Madrid (Abstract 929O_PR).

"The results clearly demonstrate that, although well-tolerated, using weekly scheduling to achieve dose-intensification of paclitaxel as part of the first-line treatment of epithelial ovarian cancer does not extend progression-free survival in this population," said study investigator Andrew Clamp, PhD, from The Christie NHS Foundation Trust and The University of Manchester, U.K. "Therefore, this approach cannot be recommended as a standard-of-care treatment option for this population."

However, he added "it remains appropriate to continue to offer weekly dose-dense paclitaxel as a treatment option to Japanese women."

The conflicting recommendations stem from the fact that findings from ICON8 contrast with those of JGOG3016, a previously reported study of Japanese ovarian cancer patients that showed significantly increased median progression-free survival (PFS) and overall survival (OS) in those treated with dose-dense weekly paclitaxel compared to the standard 3-weekly schedule.

To evaluate for a similar effect from weekly paclitaxel, ICON8 randomised 1,566 predominantly European patients to receive six cycles of either the standard 3-week dosing regimen (carboplatin AUC 5/6-paclitaxel 175 mg/mq; Arm 1), compared to two different regimens that included once-weekly dose-dense paclitaxel (carboplatin AUC 5/6+paclitaxel 80 mg/mq weekly, Arm 2; and carboplatin AUC2+paclitaxel 80 mg/mq weekly, Arm 3). All patients entered ICON8 after immediate primary surgery, or received neoadjuvant chemotherapy with planned delayed primary surgery.

The study found no benefit to either of the once-weekly regimens. PFS was 24.4 months with standard dosing, compared to 24.9 months and 25.3 months in Arms 2 and 3, respectively. In terms of toxicity, there was a slight increase in grade 3-4 toxicity in Arms 2 and 3 compared to Arm 1 (63% vs. 53% vs. 42%, respectively), although this increase was predominantly due to uncomplicated hematological toxicity.

Noting that the study was "robust and appropriately powered," Clamp said it is "not entirely clear" why ICON8 and JGOG3016 showed contrasting results. "Both were well-conducted trials and achieved the goal of increasing paclitaxel dose-intensity. We know the histological profile of ovarian cancer is slightly different between Japanese and Caucasian women, but I think it is unlikely that this accounts for the difference. It is more likely that there are pharmacogenomic differences between these two ethnic groups that account for the different results seen."

Commenting for ESMO, Domenica Lorusso, MD, PhD, from Fondazione IRCCS National Cancer Institute of Milan, Chair of the Gynecological Tumors track at ESMO 2017, said: "The trial confirms that carboplatin-paclitaxel every 3 weeks is the standard first-line treatment in ovarian cancer, a standard which has remained unmodified in the last 20 years, at least in the Caucasian population."

Lorusso agreed that success with weekly dosing in the Japanese population "is possibly due to genetic differences. According to the  5th Ovarian Cancer Consensus Conference, standard options to be discussed with the patients for first-line ovarian cancer treatment include carboplatin-paclitaxel every 3 weeks, as well as the dose-dense schedule (at least in the Japanese populations).​