Details

Autor(en) / Beteiligte

• Gore, Martin
• Hackshaw, Allan
• Brady, William E.
• Penson, Richard T.
• Zaino, Richard
• McCluggage, W. Glenn
• Ganesan, Raji
• Wilkinson, Nafisa
• Perren, Timothy
• Montes, Ana
• Summers, Jeffrey
• Lord, Rosemary
• Dark, Graham
• Rustin, Gordon
• Mackean, Melanie
• Reed, Nicholas
• Kehoe, Sean
• Frumovitz, Michael
• Christensen, Helen
• Feeney, Amanda
• Ledermann, Jonathan
• Gershenson, David M.

Titel

An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor

Ist Teil von

• Gynecologic oncology, 2019-06, Vol.153 (3), p.541-548

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer. We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II–IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL). The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3–4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms. mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782. •mEOC/GOG-0241 is one of the first international rare tumor trials.•Oxaliplatin/capecitabine might be worth further study. Long-term follow-up is feasible in rare tumors.•Challenges were lack of local resources and funding for experimental licenced therapies.