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Studies offer contradictory data for carboplatin plus liposomal doxorubicin in ovarian cancer
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2009 ASCO Annual Meeting
Two studies presented at ASCO this year demonstrated mixed results on the use of carboplatin plus pegylated liposomal doxorubicin in the treatment of patients with ovarian cancer.
Data from the Multicenter Italian Trials in Ovarian Cancer — or MITO — demonstrated that carboplatin plus liposomal doxorubicin did not improve survival in patients with advanced ovarian cancer compared with standard therapy. The experimental dose was, however, associated with increased toxicities.
“For the preliminary conclusion of our trial, we can state that the toxicity profile of carboplatin and LD in first-line is markedly different from carboplatin and paclitaxel,” Sandro Pignata, MD, PhD, medical oncology, department of uro-gynecology, National Tumor Institute, Naples, Italy, said during his presentation.
The phase-3 study included 820 patients aged 75 or younger with advanced ovarian cancer. Patients were randomly assigned carboplatin plus paclitaxel or carboplatin plus liposomal doxorubicin (CLD) for six cycles. The primary endpoint was PFS. However, Pignata presented data on the secondary endpoints: objective response rate and toxicity.
As of May 2009, with a median 35 months of follow-up, the researchers observed 531 progressions and 269 deaths. To date, median PFS was 17.7 months and median OS was 56.3 months. Objective response rates were 59% for carboplatin plus paclitaxel vs. 57% for CLD (P=.70).
Among patients with non-target lesions, complete response was 33% for carboplatin plus paclitaxel vs. 29% for CLD. Among patients with elevated CA-125, normalization occurred in 83% of those assigned to carboplatin plus paclitaxel vs. 86% of those assigned to CLD.
The researchers observed significant differences in toxicity. Compared with carboplatin plus paclitaxel, CLD was associated with increased anemia (59% vs. 68%) and thrombocytopenia (19% vs. 48%). CLD was also associated with an increase in stomatitis and skin toxicity, but with a lower incidence of alopecia and neurotoxicity.
“There was no statistically significant difference in response rate between CLD and carboplatin plus paclitaxel,” Pignata said. “Of course we will wait for the final analysis of the primary endpoint (PFS), which will be performed as soon as possible.”
Platinum-sensitive ovarian cancer
According to data from the CALYPSO study of the Gynecologic Cancer Intergroup, adding pegylated liposomal doxorubicin (PLD) to carboplatin improved PFS and was well tolerated in patients with relapsed, platinum-sensitive ovarian cancer compared with carboplatin plus paclitaxel.
Patients were randomly assigned to carboplatin plus paclitaxel (n=508) or carboplatin plus pegylated liposomal doxorubicin (n=466). The primary endpoint was PFS. OS, toxicity and quality of life were secondary endpoints. Median follow-up was 22 months.
PFS was superior in the PLD arm compared with carboplatin-paclitaxel (11.3 months vs. 9.4 months; HR=0.82; 95% CI, 0.72-0.94). OS data are unavailable; though to date the researchers report 824 progressions or death and 322 deaths.
Grade-2 and –3/4 hypersensitivity to treatment was worse in the carboplatin-paclitaxel arm compared with PLD (10% vs. 3% and 9% vs. 2%; P<.001). According to Eric Pujade-Lauraine, MD, department of oncology, Hotel Dieu Hospital, Paris, who presented the data, physicians should be aware of this finding when treating patients with ovarian cancer.
More severe neutropenia was reported in the carboplatin-arm, though more severe thrombocytopenia was reported in the PLD arm. Similar to Pignata et al, researchers from CALYPSO reported a decrease in alopecia (P<.001) and neuropathy with PLD.
“In this trial, the carboplatin-PLD demonstrated a superior therapeutic index vs. the current standard (carboplatin and paclitaxel),” Pujade-Lauraine said. “These results will change practice, as PLD-carboplatin offers an evidence-based option for platinum-sensitive, recurrent ovarian cancer.” – by Stacey L. Adams
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