TY - JOUR
T1 - An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up
T2 - and experience of conducting a clinical trial in a rare gynecological tumor
AU - Gore, Martin
AU - Hackshaw, Allan
AU - Brady, William E.
AU - Penson, Richard T.
AU - Zaino, Richard
AU - McCluggage, W. Glenn
AU - Ganesan, Raji
AU - Wilkinson, Nafisa
AU - Perren, Timothy
AU - Montes, Ana
AU - Summers, Jeffrey
AU - Lord, Rosemary
AU - Dark, Graham
AU - Rustin, Gordon
AU - Mackean, Melanie
AU - Reed, Nicholas
AU - Kehoe, Sean
AU - Frumovitz, Michael
AU - Christensen, Helen
AU - Feeney, Amanda
AU - Ledermann, Jonathan
AU - Gershenson, David M.
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/6
Y1 - 2019/6
N2 - Objectives: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer. Methods: 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). Results: 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. Conclusion: 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.
AB - Objectives: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer. Methods: 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). Results: 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. Conclusion: 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.
KW - Chemotherapy
KW - Factorial design
KW - Mucinous ovarian cancer
KW - Rare tumor trial
UR - http://www.scopus.com/inward/record.url?scp=85064316287&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064316287&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2019.03.256
DO - 10.1016/j.ygyno.2019.03.256
M3 - Article
C2 - 31005287
AN - SCOPUS:85064316287
SN - 0090-8258
VL - 153
SP - 541
EP - 548
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -