Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study

Abstract

Purpose: The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery.

Materials and methods: Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2 for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics.

Results: Of 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard-arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard (P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1-sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1-sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow-up of 39.5 months, 82 patients progressed and 37 died. The median progression-free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory.

Conclusion: HIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer.

Trial registration: ClinicalTrials.gov NCT01767675.

Conflict of interest statement

Dennis S. ChiLeadership: CSurgeriesStock and Other Ownership Interests: Bovie Medical, Verthermia, Intuitive Surgical, TransenterixConsulting or Advisory Role: Bovie Medical, Verthermia, Biom'up Alexia IasonosStock and Other Ownership Interests: Bristol Myers Squibb/SanofiConsulting or Advisory Role: Mylan, BrightPath Biotheraputics, Intelligencia Jason A. KonnerConsulting or Advisory Role: Immunogen, AstraZeneca, Tesaro, AbbVieResearch Funding: Genentech/RocheTravel, Accommodations, Expenses: AstraZeneca Vicky MakkerHonoraria: Eisai, Merck, Karyopharm Therapeutics, IBM Watson HealthConsulting or Advisory Role: Eisai, Merck, Karyopharm Therapeutics, Takeda, ArQule, IBM Watson Health, GlaxoSmithKline, Clovis Oncology, FaethResearch Funding: Lilly, AstraZeneca, Eisai, Merck, Bristol Myers Squibb, Karyopharm Therapeutics, Takeda, Clovis Oncology, Bayer, ZymeworksTravel, Accommodations, Expenses: Eisai, Merck, Karyopharm TherapeuticsOther Relationship: IBM Rachel N. GrishamConsulting or Advisory Role: Mateon Therapeutics, Clovis Oncology, Regeneron, GlaxoSmithKlineResearch Funding: Context TherapeuticsTravel, Accommodations, Expenses: EMD SeronoOther Relationship: Prime Oncology, MCM Education, OncLive, Aptitude HealthUncompensated Relationships: Verastem Amy K. BrownSpeakers' Bureau: TesaroResearch Funding: Tesaro, AstraZeneca John P. DiazSpeakers' Bureau: AstraZeneca Carrie L. LangstraatOther Relationship: Eight Medical, Covidien/Medtronic, ConMed Yulia LakhmanStock and Other Ownership Interests: Y-mAbs Therapeutics Krysten SoldanConsulting or Advisory Role: EisaiTravel, Accommodations, Expenses: Clovis Oncology Ginger J. GardnerHonoraria: BioAscentTravel, Accommodations, Expenses: BioAscent Elizabeth L. JewellHonoraria: SurvivornetConsulting or Advisory Role: Intuitive Surgical, Covidien/MedtronicResearch Funding: Summit Biomedical Tiffany Troso-SandovalHonoraria: Bio AscendTravel, Accommodations, Expenses: Bio Ascend Stuart M. LichtmanConsulting or Advisory Role: Remedy One, Magellan Health Nadeem R. Abu-RustumHonoraria: Prime OncologyResearch Funding: Stryker/Novadaq, GrailTravel, Accommodations, Expenses: Prime Oncology Carol AghajanianConsulting or Advisory Role: Mersana, Eisai, Roche, AbbVie, Eisai, AstraZeneca/Merck, Roche/Genentech, Repare TherapeuticsResearch Funding: Genentech/Roche, AbbVie, Clovis Oncology, AstraZeneca Jan BeumerEmployment: Voisin ConsultingStock and Other Ownership Interests: GlaxoSmithKlineConsulting or Advisory Role: GNS HealthcareResearch Funding: AbbVie, Spectrum Pharmaceuticals, TriSalus Life SciencesPatents, Royalties, Other Intellectual Property: Sulphoraphane for Melanoma ChemopreventionExpert Testimony: PfizerUncompensated Relationships: Qrono Yukio SonodaPatents, Royalties, Other Intellectual Property: Pending Patent for a surgical instrument (uterine manipulator) Roisin E. O'CearbhaillHonoraria: GlaxoSmithKlineConsulting or Advisory Role: GlaxoSmithKlineResearch Funding: Juno Therapeutics, Sellas Life Sciences, Ludwig Institute for Cancer Research, Stem CentRx, TapImmune Inc, TCR2 Therapeutics, Regeneron, Genmab, Atara Biotherapeutics, GlaxoSmithKline, AstraZeneca/Merck, Syndax, Genentech, Kite/Gilead, Gynecologic Oncology Group FoundationTravel, Accommodations, Expenses: AstraZenecaOpen Payments Link: https://openpaymentsdata.cms.gov/physician/785539No other potential conflicts of interest were reported.

Figures

FIG 1.

CONSORT diagram. HIPEC, hyperthermic intraperitoneal chemotherapy; IV, intravenous; OS, overall survival; PFS, progression-free survival.

FIG 2.

HIPEC carboplatin pharmacokinetics at (A) 24 hours and (B) 6 hours post HIPEC with carboplatin. HIPEC, hyperthermic intraperitoneal chemotherapy.

FIG 3.

(A) PFS by treatment arm. Kaplan-Meier survival plots of PFS. (B) OS by treatment arm. Kaplan-Meier survival plots of OS. HIPEC, hyperthermic intraperitoneal chemotherapy; OS, overall survival; PFS, progression-free survival.

FIG A1.

Forest plot for baseline variables and HR for progression or death. HIPEC, hyperthermic intraperitoneal chemotherapy; HR, hazard ratio; VUS, variant of unknown significance; WT, wild type.

FIG A2.

Forest plot for baseline variables and HR for death. HIPEC, hyperthermic intraperitoneal chemotherapy; HR, hazard ratio; VUS, variant of unknown significance; WT, wild type.