Abstract discussant Deborah K. Armstrong, MD, of Johns Hopkins Kimmel Cancer Center Baltimore, elucidated the rationale for intraperitoneal (IP) treatment, which is the peritoneal pharmacokinetic advantage for many drugs used in ovarian cancer, including carboplatin, as used in the iPocc trial.1 In addition to iPocc, Dr. Armstrong noted the use of IP carboplatin in GOG-252, in the Krasner et al trials, and as treatment after interval debulking surgery in OV21/PETROC.2-4
“The Krasner studies documented that IP administration of carboplatin resulted in substantial plasma levels and a modest shift of the curve to the right,” said Dr. Armstrong. “In contrast, IP paclitaxel has one to two logs lower plasma levels compared with IV [intravenous] paclitaxel, likely related to slow absorption of the large paclitaxel molecule and first pass metabolism of paclitaxel in the liver.”
Deborah K. Armstrong, MD
According to Dr. Armstrong, the most unique feature of the iPocc trial was the substantial fraction of patients with bulky suboptimal disease who “clearly benefited from the treatment,” as most prior IP trials were largely limited to patients with optimally debulked disease. As seen from GOG-172 data, she continued, the benefit of IP therapy was equivalent, as measured by the relative risks in those with R0 or microscopic disease and those with visible residual disease.5
“Dr. Fujiwara challenges the traditional theory with pharmacokinetic data supporting combined peritoneal and systemic exposure resulting from IP carboplatin,” said Dr. Armstrong. “Dr. Fujiwara also referenced reports indicating the benefits of IP therapy for individuals with a BRCA mutation or other potential measures of homologous recombination deficiency…. Measures of homologous recombination deficiency and proficiency should be reported in all trials including IP trials.”
Dr. Armstrong concluded: “IP therapy is a viable option for patients with bulky disease, but questions remain about its potential use as neoadjuvant therapy. We also must decide how best to incorporate maintenance therapies such as bevacizumab and PARP [poly (ADP-ribose) polymerase] inhibitors.”
DISCLOSURE: Dr. Armstrong has served as a consultant or advisor to AbbVie and Eisai; has received institutional research funding from AstraZeneca, Clovis Oncology, Eisai, Pfizer, and Syndax; and has held other relationships with AstraZeneca.
REFERENCES
1. Armstrong DK: Distillation: iPocc and SORAYA. 2022 SGO Annual Meeting on Women’s Cancer. Abstract 243. Presented March 19, 2022.
2. Walker JL, Brady MF, Wenzel L, et al: Randomized trial of intravenous versus intraperitoneal chemotherapy plus bevacizumab in advanced ovarian carcinoma: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol 37:1380-1390, 2019.
3. Krasner CN, Castro C, Penson RT, et al: Final report on serial phase II trials of all-intraperitoneal chemotherapy with or without bevacizumab for women with newly diagnosed, optimally cytoreduced carcinoma of Müllerian origin. Gynecol Oncol 153:223-229, 2019.
4. Provencher DM, Gallagher CJ, Parulekar WR, et al: OV21/PETROC: A randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer. Ann Oncol 29:431-438, 2018.
5. Armstrong DK, Bundy B, Wenzel L, et al: Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354:34-43, 2006.
