Study Confirms Adjuvant Intraperitoneal Chemotherapy Is Beneficial and Well Tolerated

Helen J. Mackay, MD

Intraperitoneal chemotherapy (IP) is beneficial and tolerable, and physicians should present it as an option to women who have had successful cytoreductive surgery for their advanced epithelial ovarian cancer (EOC), according to initial results from the randomized phase II OV21/PETROC trial reported at the 2016 ASCO Annual Meeting.

The study found that women who received part of their adjuvant chemotherapy regimen using the IP approach had nearly a 19% reduction in progressive disease, compared with their counterparts whose chemotherapy was delivered only intravenously.

Researchers hope that the findings of this pragmatic study, presented by Helen J. Mackay, MD, in a press briefing on June 3, 2016, will provide more clarity for clinicians on how to incorporate IP treatment for women with EOC, which is the leading cause of gynecologic cancer mortality, projected to account for 14,240 deaths in the United States this year, according to ASCO.

Mackay, who is divisional head of medical oncology and hematology at the Sunnybrook Odette Cancer Centre in Toronto, Canada, noted that because the early stages of the disease are asymptomatic, approximately two-thirds of women with ovarian cancer have stage III/IV disease when they are diagnosed. She added that the use of neoadjuvant chemotherapy has increased in recent years, with approximately 40% of women with EOC receiving chemotherapy prior to surgery. The aim of OV21/PETROC was to determine whether this group of patients, who typically undergo more chemotherapy after surgery, would benefit from having that chemotherapy delivered intraperitoneally.

The data Mackay reported at ASCO are based on a comparison of two groups of women (a third arm of the trial [arm 2], which used cisplatin rather than carboplatin, was dropped after a planned data and safety monitoring committee review). To be eligible for the study, women had a diagnosis of EOC, fallopian tube, or primary peritoneal cancer stage IIB-IV at diagnosis and had received neoadjuvant chemotherapy followed by optimal debulking surgery (with remaining tumors measuring <1 cm).

After surgery, patients in the intravenous (IV) arm of the study (arm 1; n = 101) were treated with IV paclitaxel (135 mg/m²) and IV carboplatin (AUC 5/6) on day 1, followed by IV paclitaxel (60 mg/m²) on day 8, over three 21-day cycles. The comparator cohort (arm 3; n = 102) received the same regimen, but the carboplatin and the paclitaxel on day 8 were delivered IP.

The study’s primary endpoint was the progressive disease (PD) rate at 9 months after randomization. For women in the IV-only arm, the PD rate was 42.2% (95% CI, 29.1%-48.8%), whereas for women in the IP arm, the 9-month PD rate was 24.5% (95% CI, 16.6%-34%), equivalent to a reduction in the PD rate of 18.9%, Mackay reported.

Although the trial was not powered to detect differences in overall survival (OS), Mackay said the hazard ratio proved similar to that observed in other intraperitoneal trials which showed benefit using the approach in the frontline setting. The median OS was 59.3 months in the IP arm versus 38.1 months using IV (HR, 0.80; 95% CI, 0.47-1.35; P = .40).

Notably, the IP was well-tolerated, Mackay said. Quality-of-life data did not differ between the IV and IP arms and improved over time.

Panel moderator and ASCO Expert in ovarian cancer Don Dizon, MD, FACP, said that this study should “provide reassurance for patients and providers that the carboplatin-based IP regimen is both effective and well-tolerated with maintenance of quality of life.”

He added that the research is illustrative because it studied IP treatment in a novel way. “This looked at women with advanced ovarian cancer, all of whom received primary chemotherapy before surgery, and in that group of women, we have not known what the best strategy is.”

“While this is not a phase III study, I think the data are very provocative and suggest that there is a role for IP therapy for such patients.”

The findings also are important in light of results of the phase III GOG 252 study,² presented at the 2016 Annual Meeting of the Society of Gynecologic Oncology in March, which suggested that IP therapy was not superior to IV treatment. Those findings sparked controversy at the time and left both patients and doctors “scratching their heads,” according to the Ovarian Cancer Research Fund, which advised patients, in a statement issued after GOG 252’s findings were announced, not to “abandon IP chemotherapy.”

Mackay explained that the OV21/PERTOC trial results reported at ASCO differ from the GOG 252 study in several ways:

“In GOG 252, around 30% [of tumors] were not of the high-grade serous more common histology (that predominated in OV21/PERTOC). Also, the addition of bevacizumab led to toxicities.” She added that “there is a question about whether the 75 mg/m2 of cisplatin is as efficacious as the 100 mg/m², and the final survival data on the optimally debulked, cytoreduced patients have not been made available.”

“I don’t think the GOG 252 trial was informative on the role of intraperitoneal chemotherapy, predominantly because everybody on that study got bevacizumab, and the toxicity was concerning across the arms,” Dizon noted, concluding that the OV21/PERTOC findings reported at ASCO add to the understanding of the role of intraperitoneal chemotherapy.

“For women with optimally cytoreduced or completely resected ovarian cancer, whether or not they got neoadjuvant chemotherapy, intraperitoneal chemotherapy must be an option that is discussed.”

To further elucidate the role of IP in the treatment of ovarian cancer and better define which patients will truly benefit from this approach, the researchers are conducting correlative studies on tissue samples collected during this study to determine whether certain biologic characteristics may be associated with improved outcomes using IP versus IV chemotherapy.

1. Mackay H, Gallagher CJ, Parulekar WR, et al. OV21/PETROC: a randomized Gynecologic Cancer Intergroup (CGIG) phase II study of intraperitoneal (IP) versus intravenous (IV) chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer (EOC). J Clin Oncol. 2016 (suppl; abstr LBA5503).
2. Walker JL, Brady MF, DiSilvestro PA, et al. A phase III clinical trial of bevacizumab with IV versus IP chemotherapy in ovarian, fallopian tube and primary peritoneal carcinoma NCI-supplied agent(s): bevacizumab (NSC #704865, IND #7921) NCT01167712 a GOG/NRG trial (GOG 252). Presented at: 2016 SGO Annual Meeting. March 19-22, 2016. San Diego, CA. Late-breaking abstract.

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