Conference Coverage

Superiority of Dose-Dense Chemo Upheld for Ovarian Cancer


 

AT THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY

CHICAGO – The superiority of dose-dense paclitaxel-plus-carboplatin chemotherapy stood up in the long term for women with ovarian or related cancers in a randomized trial.

Investigators from the Japanese Gynecologic Oncology Group 3016 study reported statistically significant reductions in risks of progression and of death with dose-dense chemotherapy, compared with a conventional regimen, at a median follow-up of 6.4 years.

Women who were given dose-dense chemotherapy had the risk of progression or death cut by 24% and the risk of death cut by 21%, according to results reported at the annual meeting of the American Society of Clinical Oncology. This followed respective reductions of 29% and 25% at a median follow-up of 2.4 years (Lancet 2009;374:1331-8).

In subgroup analyses, the survival benefit of dose-dense chemotherapy was significant only among women who had residual disease after debulking surgery measuring greater than 1 cm, or serous histology.

"Dose-dense [paclitaxel plus carboplatin] improved long-term progression-free survival and overall survival in patients with advanced epithelial ovarian cancer," said first author Dr. Noriyuki Katsumata of the Nippon Medical School–Musashi-Kosugi Hospital in Kawasaki, Japan.

"Neither dose-dense nor conventional treatment seemed effective against clear-cell or mucinous ovarian carcinoma, which suggests that other treatment strategies are needed," he added.

The study "is a major contribution to our understanding of dose-dense therapy and whether or not it should be used," said the invited discussant, Dr. Jonathan S. Berek, director of the Stanford (Calif.) Women’s Cancer Center. In particular, the overall survival benefit "is a very important observation for our patients and our specialty."

However, the trial was done in a Japanese population, he cautioned. "Maybe there are racial differences. We’ll have to wait for confirmatory trials to see whether there is any difference. There may be none, but we’ll see."

"One of the questions I’d like to raise is, how does this compare to the advantage that we saw with intraperitoneal therapy, and what should we recommend to our patients while we await more confirmatory and comparative data?" Dr. Berek said.

He noted that a variety of trials – GOG (Gynecologic Oncology Group)–0252, GOG-0262, ICON8, MITO-7, and iPocc – will better clarify and compare the merits of dose-dense and intraperitoneal approaches, sometimes in combination with the antiangiogenic agent bevacizumab (Avastin).

"I suspect in the next 2-3 years, the head-to-head comparison of the dose-dense regimens and the intraperitoneal regimens will emerge, and we will probably have at least some clear answers about whether it’s route of administration or frequency of administration, or in some cases, both" that optimizes efficacy, Dr. Berek concluded.

The 637 women accrued to the Japanese trial, also known as the NOVEL study, had advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer and had undergone debulking surgery. The large majority (84%) had serous tumor histology.

They were randomly assigned to paclitaxel (Taxol) plus carboplatin given according to a conventional schedule (paclitaxel, 180 mg/m2; carboplatin, AUC [area under the curve] = 6; each given once every 3 weeks) or according to a dose-dense schedule (paclitaxel, 80 mg/m2 weekly; carboplatin, AUC = 6 once every 3 weeks), in both arms for six to nine cycles.

The updated results showed that relative to conventional chemotherapy, dose-dense chemotherapy conferred better median progression-free survival (28.2 vs. 17.5 months, respectively; hazard ratio, 0.76; P = .004) and overall survival (not reached vs. 62.2 months; HR, 0.79; P = .04). At this point, 58.7% of the dose-dense group and 51.1% of the conventional therapy group were alive.

In analyses stratified by the extent of residual disease after debulking surgery, the overall survival benefit of dose-dense chemotherapy was significant only for women who had residual disease measuring greater than 1 cm (median, 51.2 months vs. 33.5 months; HR, 0.75; P = .03) or serous histology (median, not reached vs. 61.2 months; HR, 0.76; P = .03).

In a multivariate analysis, dose-dense chemotherapy was a significant independent predictor of overall survival, along with ovarian disease site, earlier stage, less residual disease, better performance status, and a paclitaxel relative dose intensity of at least 80%.

Dr. Katsumata disclosed no relevant conflicts of interest. Dr. Berek disclosed no relevant conflicts of interest.

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