Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer
- Study type
- Clinical trial
- Study name
- EORTC 55971
- Phase
- Phase 3
- Design
- Randomised, multicentre trial with a noninferiority design
- Sample size
- 670 patients were randomised; 632 patients (94.3%) were eligible and started treatment
- Source
- N Engl J Med · 2010
- Trial registration
- NCT00003636
In plain words
In this large study, patients with advanced ovarian cancer were given one of two treatment approaches: surgery first and then chemotherapy, or chemotherapy first and then surgery. The results showed that survival did not differ in any important way between the two approaches, and the "chemotherapy first" approach was not worse than the other. Complications and deaths after surgery tended to be more common with the "surgery first" approach. With both approaches, removing all visible tumour was the most important factor for better survival.
Key results
Treatment arms and regimens
Primary debulking surgery with maximal effort by a gynaecological oncology surgeon, followed by at least 6 cycles of platinum-based chemotherapy (per the ClinicalTrials.gov registration: IV cisplatin or carboplatin every 3 weeks). In patients in whom optimal cytoreduction was not achieved and whose disease was stable or responding, interval surgery was allowed (no longer recommended after the GOG-152 results were published). The chemotherapy regimens and doses are given only in the paper's appendix and are not stated in the text of the paper or the trial registration (336 patients).
3 cycles of platinum-based neoadjuvant chemotherapy (IV cisplatin or carboplatin every 3 weeks per the trial registration), then interval debulking surgery in all patients with response or stable disease, followed by at least 3 further cycles of the same chemotherapy; the dose is not stated in the text of the paper or the trial registration (334 patients).
Source of the regimen details: Full text of the paper (Radboud University repository version, Study Design section) and ClinicalTrials.gov NCT00003636 (IV cisplatin or carboplatin every 3 weeks); the type and dose of the regimens are given only in the paper's appendix, which was not available to us
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 with histologically confirmed stage IIIC or IV invasive epithelial ovarian carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma; in the absence of a biopsy, fine-needle aspiration showing adenocarcinoma was accepted provided there was a pelvic mass, metastases of at least 2 cm outside the pelvis (or regional lymph node metastases or stage IV) and a CA-125 to CEA ratio above 25. WHO performance status 0 to 2 and no debilitating disease precluding surgery or platinum-based chemotherapy. Enrolment from September 1998 to December 2006 in 59 centres. Most patients had extensive disease: metastatic lesions larger than 5 cm in 74.5% and larger than 10 cm in 61.6% of patients.
Endpoints
The primary endpoint is not stated explicitly in the abstract; results are reported as the hazard ratio for death (intention-to-treat analysis, with a noninferiority test) and the hazard ratio for progression. Postoperative complications and mortality and residual tumour size were also assessed.
Safety and side effects
Postoperative death (within 28 days) occurred in 2.5% of patients in the primary surgery group and 0.7% of the neoadjuvant chemotherapy group. Grade 3 or 4 haemorrhage in 7.4% after primary surgery versus 4.1% after interval surgery, infection in 8.1% versus 1.7% and venous complications in 2.6% versus 0% (no statistical comparison was made because the groups were not equal in terms of surgery received). The global quality-of-life score (QLQ-C30) did not differ significantly at any time point.
Clinical significance and place in guidelines
According to the abstract, neoadjuvant chemotherapy followed by interval debulking surgery can be an alternative to primary surgery for patients with bulky stage IIIC or IV ovarian cancer, and the goal of surgery in both settings is complete resection of all macroscopic disease. The status of this approach in current clinical guidelines should be checked separately.
Limitations
The conclusions of this study are limited to patients with bulky stage IIIC or IV disease. According to the abstract, complete resection of all macroscopic disease is the strongest independent predictor of survival, and this is an independent variable, not a randomised one. Other limitations should be checked in the full text of the paper.
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.