Kate Johnson

June 05, 2016

CHICAGO — Intraperitoneal (IP) chemotherapy is now an alternative to intravenous (IV) administration that "must be discussed" for women with cytoreduced ovarian cancer, several experts said here at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.

But the phase 2 data that prompted those comments "will do nothing to settle the controversy" surrounding the choice of IP or IV therapy, Richard Schilsky, MD, ASCO chief medical officer, told Medscape Medical News.

As previously reported by Medscape, despite better outcomes with IP chemo, reported as far back as 2001, this approach is underutilized largely because of toxicities and difficulties with administration.

But now two prospective studies suggest that a switch from a cisplatin- to a carboplatin-based IP regimen might overcome some barriers.

The findings demonstrate "the potential clinical utility of this route of drug delivery...both in routine clinical care and in the development of innovative clinical trial concepts in ovarian cancer," Maurie Markham, MD, the discussant for both studies, told Medscape Medical News. "These were both small studies and one always needs to wait for the peer-reviewed publications," he added.

But, he concluded in his presentation, "the IP strategy may be appropriately considered one potential approach...rather than either a mandated or discarded concept...in the evolving management of ovarian cancer."

"IP chemotherapy is an effective yet underused treatment," added Don Dizon, MD, ASCO expert in ovarian cancer. "For women with optimally cytoreduced or completely resected ovarian cancer, whether or not they received neoadjuvant chemotherapy, intraperitoneal chemotherapy must be an option that is discussed," he said at a press briefing.

New Studies With Carboplatin

The two new studies used different combinations of IV paclitaxel combined with IP carboplatin in different populations with advanced disease.

Dr Helen Mackay

The OV21/PETROC study, which was selected as a late-breaking abstract and highlighted in the press program, randomized women with epithelial ovarian cancer after neoadjuvant IV chemotherapy and debulking surgery, reported Helen Mackay, MD, head of medical oncology and hematology at Sunnybrook Odette Cancer Centre in Toronto.

All patients received IV paclitaxel, but women in group 1 (n = 101) also received IV carboplatin, and those in group 3 (n = 102) received IP carboplatin. (However, the group in which patients received IV cisplatin was abandoned on the basis of efficacy advice from an independent data safety monitoring committee).

For the primary end point of the trial, progressive disease rate at 9 months, the per protocol results showed that IP-treated patients fared significantly better than IV-treated patients (23.3% vs 42.2%; P value unstratified = .01).

And although the trial was not powered to detect a difference in overall survival, "the hazard ratio was similar to what we've seen in other intraperitoneal trials," said Dr Mackay, showing a median overall survival (defined as time from randomization to disease progression) of 38.1 months in IV patients and 59.3 months in IP patients (hazard ratio [HR], 0.8; P = .40).

In terms of toxicity, "IP carboplatin was well tolerated; quality-of-life data did not differ between the arms and improved with time," she said.

"I would say at this time, for the upfront cytoreduced patient, and also for the neoadjuvant patient, that intraperitoneal chemotherapy remains an option for discussion," she said. "We need to learn more about the biology and the potential predictive signatures."

Dr Don Dizon

"This study provides reassurance for patients and providers that the carboplatin-based IP regimen is both effective and well tolerated with maintenance of quality of life," Dr Dizon said in statement. "That said, we need to further define those who derive the greatest benefit from this approach," he added.

The second study presented at the meeting was unrandomized and evaluated 71 women with stage II to IV ovarian or primary peritoneal carcinoma who completed at least one cycle of IV dose-dense paclitaxel and IP carboplatin (ddTCip) after primary cytoreductive surgery.

A total of 46 patients (60.5%) completed six or more cycles, but with many interruptions because of toxicity, reported Kosei Hasegawa, MD, PhD, from Saitama Medical University International Medical Center in Hidaka, Japan.

Overall, 83.1% of patients had an objective response, including complete response (12.7%), partial response (70.4%), and stable disease (14.1%), he said.

Median progression-free survival was 18.3 months, and median overall survival was 55.5 months.

With the exception of the port-related adverse events rate (11.8%), the regimen's toxicity profile was similar to that seen in the dose-dense group of a previous trial (JGOG3016), said Dr Hasegawa.

Grade 3/4 toxicities included neutropenia (84.2%), anemia (56.5%), and thrombocytopenia (22.4%). "We suggest that the frontline chemotherapy with ddTCip therapy is safe and effective, even for suboptimal residual ovarian carcinoma patients," he concluded.

Dr Schilsky has disclosed no relevant financial relationships. Dr Markman reports a consulting or advisory role with Amgen, Celgene, CritiTech, and Pfizer; being on the speaker's bureau for AstraZeneca and Genentech/Roche; and providing expert testimony for CORN Research, Actavis, Apotex, Dr Reddy's laboratory, Emcure, Fresenius Kabi, Hikma Pharmaceuticals, Hospira, Pharmaceuticals International, Sagent, Strides, Sun Pharma, and Wockhardt Pharmaceuticals. Dr Dizon reports receiving research funding from Aeterna Zentaris. Dr Mackay reports receiving travel, accommodations, expenses from AstraZeneca. Dr Hasegawa reports receiving honoraria from Chugai Pharma;, and Ono Pharmaceutical.

American Society of Clinical Oncology (ASCO) 2016 Annual Meeting: Abstract LBA5503, presented June 5, 2016; Abstract 5504, presented June 3, 2016.

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