Clinical trialPhase 3Ovarian cancer

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial

Lancet Oncol · 2023245 patients (123 surgery alone and 122 surgery with HIPEC)

Aronson SL, Lopez-Yurda M, Koole SN, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, et al. Lancet Oncol. 2023. 24:1109-1118

Study type: Clinical trial
Study name: OVHIPEC-1
Phase: Phase 3
Design: Randomised, open-label, controlled trial — final analysis after 10 years of follow-up
Sample size: 245 patients (123 surgery alone and 122 surgery with HIPEC)
Source: Lancet Oncol · 2023
Trial registration: NCT00426257

In plain words

In this study, women with stage III ovarian cancer who had first received chemotherapy either had surgery alone to remove the tumour, or had surgery plus washing of the inside of the abdomen with a warm chemotherapy drug (cisplatin). After about ten years of follow-up, the HIPEC group lived a median of about 11 months longer. This procedure is done only in experienced centres. Decisions about treatment should be made with your treating doctor.

Key results

44.9 months vs 33.3 months

Median overall survival

HR 0.70 (0.53 to 0.92); p=0.011

14.3 months vs 10.7 months

Median progression-free survival

HR 0.63 (0.48 to 0.83); p=0.0008

10.4 years (HIPEC) and 10.1 years (surgery alone)

Median follow-up

Drugs in this study:Carboplatin (Paraplatin)Cisplatin (Platinol)Paclitaxel (Taxol)

Dose and schedule cards

HIPEC with cisplatin at interval debulking surgery (OVHIPEC-1)

Stage III with at least stable disease after 3 cycles of neoadjuvant chemotherapy, when complete or optimal cytoreduction (residual disease 10 mm or less) is feasibleOn the page “Ovarian cancer” · First line: chemotherapy and surgery

Stage III with at least stable disease after 3 cycles of neoadjuvant chemotherapy, when complete or optimal cytoreduction (residual disease 10 mm or less) is feasible

Drug	Dose	Route	Schedule
Before surgery: 3 cycles
Carboplatin + paclitaxel	AUC 5–6 + 175 mg/m²	IV	Day 1 every 21 days
During interval debulking surgery
Cisplatin (HIPEC)	100 mg/m²	Intraperitoneal, hyperthermic	Once
After surgery: 3 cycles
Carboplatin + paclitaxel	AUC 5–6 + 175 mg/m²	IV	Day 1 every 21 days

Cycle length: Every 21 days (IV chemotherapy)
Duration: 6 cycles in total

Grade 3–4 adverse events were similar in the two groups (27% vs 25%). The Pan-Asian ESMO guideline does not consider HIPEC a first-line standard [II, D]; only at experienced centres.

On the page “Ovarian cancer” · First line: chemotherapy and surgery

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Interval cytoreductive surgery with HIPEC (122 patients)

After at least 3 cycles of neoadjuvant carboplatin (AUC 5 to 6) + paclitaxel (175 mg/m²) every 3 weeks: interval cytoreductive surgery with HIPEC using cisplatin 100 mg/m² intraperitoneally; then 3 further cycles of carboplatin–paclitaxel after surgery.

2Interval cytoreductive surgery alone (123 patients)

The same neoadjuvant and postoperative chemotherapy (carboplatin AUC 5–6 + paclitaxel 175 mg/m², 3 + 3 cycles) and interval surgery without HIPEC.

Source of the regimen details: Abstract of the paper (HIPEC cisplatin 100 mg/m²) and abstract of the original NEJM 2018 report (carboplatin AUC 5–6 and paclitaxel 175 mg/m², 3 cycles before and 3 cycles after surgery)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients aged 18 to 76 with primary stage III epithelial ovarian cancer who were not suitable for primary surgery and had not progressed during at least three cycles of neoadjuvant carboplatin–paclitaxel; WHO performance status zero to 2.

Endpoints

Primary endpoint: progression-free survival; secondary endpoint: overall survival (intention-to-treat population).

Safety and side effects

Safety data are not given in the abstract of this final report. In the original report (NEJM 2018), grade 3 or 4 adverse events were similar in the two groups: 27% with HIPEC versus 25% without HIPEC (P=0.76).

Clinical significance and place in guidelines

The 10-year final analysis confirms the survival benefit of cisplatin HIPEC at interval surgery after neoadjuvant chemotherapy in stage III disease; however, some guidelines do not consider it a universal standard because of limitations of the evidence.

Limitations

An open-label and relatively small trial (245 patients) in specialist HIPEC centres, with randomisation at the time of surgery.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.