Women with ovarian cancer do not survive longer if they receive first-line chemotherapy with gemcitabine (Gemzar) and carboplatin, compared with the standard of care, according to a phase III trial presented during the Gynecologic Cancer Oral Abstract Session at the 2010 ASCO Annual Meeting. The final report for this multicenter trial found a similar progression-free survival (PFS) between the experimental treatment and the standard, paclitaxel plus carboplatin.¹

The results demonstrate that paclitaxel/carboplatin therapy remains the standard of care for front-line treatment of ovarian cancer, said the abstract's discussant, Ronald Buckanovich, MD, PhD, Assistant Professor of Internal Medicine and Obstetrics/Gynecology, University of Michigan Health System, Ann Arbor.

"For patients who do not tolerate taxanes, gemcitabine plus carboplatin treatment is a legitimate alternative," Dr. Buckanovich said.

Trial Stopped Early

In August 2009, the trial was stopped early, after an ad hoc futility analysis showed a low probability of a positive PFS result (the primary endpoint) in the experimental arm, according to the abstract. The study's lead researcher, Michael Teneriello, MD, a gynecologic oncologist with US Oncology, The Woodlands, Texas, presented the intent-to-treat data in 831 patients.

In explaining the rationale for this study, Dr. Teneriello said phase II trials had shown the combination of gemcitabine and cisplatin to be active as first-line chemotherapy for patients with platinum-sensitive ovarian cancer. This trial compared gemcitabine plus carboplatin with standard chemotherapy, and aimed to determine if monthly paclitaxel consolidation therapy would improve survival for patients achieving a complete response to induction chemotherapy, he said.

The investigators randomly assigned patients with stage IC through IV ovarian cancer to receive one of two treatments postoperatively. One regimen was 1,000 mg/m² of gemcitabine on days 1 and 8 of each 21-day cycle plus carboplatin (area under the curve [AUC] 5) on day 1 (n = 417). The other regimen consisted of 175 mg/m² of paclitaxel plus carboplatin (AUC 6) on day 1 (n = 414). Patient characteristics were similar in each group, Dr. Teneriello reported.

Patients with a complete clinical response after 6 cycles of chemotherapy could elect to continue paclitaxel treatment (135 mg/m²) every 28 days for 12 cycles; 352 patients received consolidation therapy. Participants who did not have a complete response received crossover therapy with single-agent gemcitabine or paclitaxel. Crossover therapy continued every 21 days for 155 patients until complete response or disease progression.

Protocol Changed

After the study began, the investigators changed the protocol so that paclitaxel consolidation therapy after complete response was elective, rather than mandatory, Dr. Teneriello said. They also changed the primary endpoint from overall survival (OS) to PFS. Secondary objectives were OS, response rate, and adverse events.

The overall response rate after induction therapy was 67.6% in the gemcitabine arm and 71.1% in the paclitaxel arm, Dr. Teneriello reported. This difference was not statistically significant. There also was no significant difference in response between the crossover arms. In the gemcitabine arm, 165 patients discontinued the study after induction therapy compared with 148 in the other arm, he said.

Regarding adverse events after induction therapy, rates of anemia, thrombocytopenia, and the need for platelet transfusion were higher in the gemcitabine arm, whereas neuropathy and alopecia occurred more often in the paclitaxel arm, according to Dr. Teneriello. Among patients who received consolidation therapy, he said the only difference in adverse events between regimens was a greater incidence of neuropathy in the paclitaxel arm. These results were consistent with prior clinical experience, he noted.

Table 1 shows survival results. The better OS in the paclitaxel arm was no longer statistically significant after adjustment for covariates, Dr. Teneriello commented. Gemcitabine appeared to improve OS in patients receiving paclitaxel consolidation therapy. However, he said, "the rate of censorship [of patient data] was in all cases more than 50% and diminishes the reliability."

Dr. Buckanovich told The ASCO Post, "If there is no PFS advantage, it would be hard to see how there was any OS advantage. We need to be careful that no one interprets this trial as showing any survival benefit." ■

Reference

1. Teneriello MG, Gordon AN, Lim P, et al: Phase III trial of induction gemcitabine (G) or paclitaxel (T) plus carboplatin (C) followed by elective T consolidation in advanced ovarian cancer (OC): Final safety and efficacy report. 2010 ASCO Annual Meeting. Abstract LBA5008. Presented June 6, 2010.