For women with advanced ovarian cancer that was successfully treated surgically, intraperitoneal (IP) chemotherapy paired with IV chemotherapy appeared more effective than IV chemo alone, researchers said here.
After neoadjuvant chemotherapy and delayed debulking surgery, intraperitoneal (IP) carboplatin-based chemotherapy was well tolerated and associated with a lower rate of progressive disease at 9 months than IV therapy, reported Helen Mackay, MD, of Sunnybrook Health Sciences Centre, Toronto, and colleagues.
OV21/PETROC was the first randomized trial to study IP for epithelial ovarian cancer in the post-neoadjuvant setting, and the results were presented at the American Society of Clinical Oncology annual meeting.
The 9-month disease progression rate was 23.3% in those treated with an IP/IV regimen versus 42.2% in patients who received IV chemotherapy, the authors noted.
However, the median progression-free survival was similar for the two groups at 12.5 months with the IV/IP regimen and 11.3 months with IV alone, for a hazard ratio of 0.82 (95% CI 0.57-1.17, P=0.27).
But the median overall survival was slightly longer with IV/IP therapy than with IV therapy alone (59.3 months vs 38.1months, HR 0.80, 95% CI 0.47-1.35, P=0.40). This difference was not statistically significant.
“Although this randomized phase I trial was not statistically powered to evaluate survival, our results offer information on how to incorporate IP chemotherapy when women receive neoadjuvant chemotherapy followed by debulking surgery,” Mackay said in an ASCO press release. “The findings also offer supportive and additional information to the previous published adjuvant randomized trials that showed an improvement in overall survival when IP chemotherapy was given following initial optimal debulking surgery.”
An earlier data analysis had found 9-month progression rates of 38.6% (95% CI 29.1-48.8) using only IV paclitaxel and carboplatin versus 24.5% (95% CI 16.5-34.0, P=0.003 stratified, P=0.01 unstratified) with the addition of IP paclitaxel and carboplatin to IV paclitaxel.
But researchers at the 2016 Society of Gynecologic Oncology meeting reported disappointing results from the Gynecologic Oncology Group 172 study of various chemotherapy combinations for ovarian cancer, including IV/IP delivery and the angiogenesis blocker bevacizumab (Avastin), with some suggestion that it may be time to move on from the IP approach
From 2009 to 2015, the OV21/PETROC trial recruited 275 patients (median age 62). The majority (81.8%) had stage IIIC disease and 12.7% had stage IV disease. The trial originally randomized well-matched patients to three arms, including a second arm that received IP cisplatin and IP carboplatin as well as IV paclitaxel. After a data and safety monitoring review, the investigators dropped the IP cisplatin arm in favor of continuing a two-arm comparison of 200 patients, which had an 80% power to detect a 19% difference in the disease progression rate at 9 months.
Patients in arm 1 received IV paclitaxel plus IV carboplatin on day 1, and IV paclitaxel on day 8. Patients in arm 3 received IV paclitaxel plus IP carboplatin on day 1, and IP paclitaxel on day 8. The median number of completed cycle in all arms was three.
Since certain molecular subtypes of ovarian cancer are more sensitive to chemotherapy, the investigators will assess tissue samples collected during the study to see if certain biologic characteristic were associated with the improved outcomes of IP delivery. “If we can identify the long-term survivors, we hope this will help us better predict who truly benefits from this approach,” Mackay said.
In terms of adverse events, grade 3 or higher toxicities affected 23% in the IV-only group 1 and 16% in the IP group (P=0.24), although the difference was not significant. IP delivery has been associated with abdominal pain and catheter site problems.
There were no significant differences between the two arms in patient quality of life or function.
ASCO press briefing moderator Don S. Dizon, MD, of Massachusetts General Hospital in Boston, called IP chemotherapy “an effective but underused treatment for women with newly diagnosed ovarian cancer that has been successfully removed surgically,” in a written statement.
Commenting on the study for MedPage Today, Maurie Markman, MD, of Cancer Treatment Centers of America, Eastern Regional Medical Center, in Philadelphia, called it “a very well-designed and well-conducted prospective study, with a very reasonable defined endpoint of 9-month disease progression rate. And while it’s only a phase II study, it’s important in that it’s the first randomized trial in the post-neoadjuvant setting.”
Markman, who was not involved in the study, added that according to these results, “IP carboplatin may well be a very rational and appropriate way of giving treatment to patients who have responded to neoadjuvant platinum-based chemotherapy and are going to continue therapy. It could be considered by individual doctors now or considered for study in further clinical trials.”
He noted that while IP delivery has been around for some 30 years, it’s more difficult, painful, and time-consuming than IV delivery, and “that extra time is not remunerated.”
Markman lauded the investigators’ rational decision to drop arm 2 on the grounds of the higher toxicity of IP cisplatin, and to patients in arm 2, and their data, into the remaining two arms. “The dosing schedule was also very appropriate, and anyone who doesn’t think so should maybe go back to school,” Markman said.
A phase II Japanese study presented at ASCO reported a near-80% clinical response rate to IP chemotherapy in patients with residual ovarian cancer after cytoreductive surgery. An ongoing phase III randomized study from Japan is expected to show superior results with IP carboplatin plus dose-dense paclitaxel than IV carboplatin in epithelial ovarian cancer.
To read the full article on MedPage Today, click here.