2438 - Phase II clinical trial of gemcitabine plus oxaliplatin combination therapy (GEMOX) in patients with advanced pancreatic adenocarcinoma with a family history of pancreatic/breast/ovarian/prostate cancer or personal history of breast/ovarian/prostate cancer (FABRIC study)

Background

Presence/absence of family/personal history of breast/ovarian/pancreatic cancer has been reported to be a useful predictive marker in patients with pancreatic adenocarcinoma (PA) receiving platinum-based chemotherapy (Fogelman D, 2015). We planned a prospective phase II study to evaluate the efficacy and safety of platinum-based chemotherapy in this population.

Methods

Eligible patients were those with chemotherapy-naïve metastatic PA with one or more of the following: 1) family history of pancreatic (P)/breast (B)/ovarian (O)/prostate (PR) cancer in a first-degree relative, 2) at least two family members with P/B/O/PR cancer within third-degree relatives, and 3) personal history of B/O/PR cancer. Patients received gemcitabine 1,000 mg/m² and oxaliplatin 100 mg/m² every two weeks (GEMOX). The primary endpoint was the one-year survival rate, and the outcome in 19 of 43 patients (pts) (44%) were desired. The target sample size was determined as 43, with a one-sided alpha of 5% and a power of 80%.

Results

A total of 45 pts were enrolled. The first consecutive 43 pts were included in the efficacy analysis. The one-year survival rate (90% confidence interval) was 27.9% (17.0-41.3) and did not meet the expected threshold. The response rate was 27.9%. A tendency towards prolonged survival was observed in patients with two or more family histories of P/B/O/PR cancer (HR 0.65, 95% CI [0.34-1.23]). Presence of a family/personal history of B/O/PR cancer tended to be associated with a better response and longer survival. In this study population, patients with a family history of pancreatic cancer seemed to show a poorer response. The most common adverse events of grade 3 or higher severity were neutropenia (36%), leukopenia (27%) and thrombocytopenia (23%).

Conclusions

GEMOX did not show expected efficacy in patients with metastatic PA with a family/personal history of P/B/O/PR cancer. Selection of GEMOX based on family/personal history alone is not recommended, especially in patients with a family history of P cancer.

Clinical trial identification

UMIN000017894 (registeration date: 17-Jun-2015).

Legal entity responsible for the study

National Cancer Center Hospital.

Funding

Japan Agency for Medical Research and Development (AMED), National Cancer Center Research and Development Fund.

Editorial Acknowledgement

Disclosure

H. Takahashi: Honoraria: Taiho Pharmaceutical; Research funding: Bayer Pharmaceutical, Bristol-Myers Squibb. C. Morizane: Honoraria: Pfizer, Novartis, Yakult Honsha, Lilly, Nobelpharma, Fujifilm, Teijin Pharma, Taiho Pharmaceutical; Consulting or advisory role: Yakult Honsha, Novartis, Taiho Pharmaceutical; Research funding (Recipient: institution): Pfizer, Nobelpharma, Eisai, Yakult Honsha, Ono Pharmaceutical, Taiho Pharmaceutical. S. Nomura: Honoraria: Taiho Pharmaceutical N. Okano: Honoraria: Taiho Pharmaceutical, Merck Serono; Research funding (Recipient: institution): J-Pharma, Taiho, Sumitomo Dainippon, Janssen, Daiichi Sankyo, MSD, Yakult, Takeda, Chugai, Ono, Astellas, Zeria, Novartis, Nanocarrier, Shionogi, Onco Therapy Science, Eli Lilly Japan, Bayer, Bristol-Myers Squibb, Merck Serono, Kyowa Hakko Kirin, Eisai, NanoCarrier, Mochida, Baxalta, Sanofi. N. Mizuno: Research funding: Taiho Pharmaceutical Co. Ltd., Merck Serono, AstraZeneca, Zeria Pharmaceutical, NanoCarrier, Eisai, MSD, Novartis, Dainippon Sumitomo Pharma, Aslan Pharmaceuticals, Pharma Valley Center, Incyte Inc. (Recipient: institution); Honoraria: Taiho Pharmaceutical Co. Ltd., Novartis, Ono Pharmaceutical, Teijin Pharma (Recipient: self); Advisory role: Teijin Pharma. H. Satake: Honoraria: Bayer, Chugai Pharma, Eli Lilly Japan, Merck Serono, Takeda, Taiho Pharmaceutical, Yakult Honsha. H. Ishii: Honoraria: Taiho, Yakult, Eisai, Towa; Consulting or advisory role: Ono; Research funding (Recipient: institution): Taiho. M. Ueno: Honoraria: Taiho Pharmaceutical, Yakult Honsha, AstraZeneca, Novartis, Lilly, Teijin Pharma, Shire, Ono Pharmaceutical; Research funding: Taiho Pharmaceutical, Shire, Daiichi Sankyo, Eisai, AstraZeneca, Ono Pharmaceutical, MSD, Merck Serono, NanoCarrier, Dainippon Sumitomo Pharma, Incyte. M. Ikeda: Honoraria: Novartis Pharma, Bayer Yakuhin, Bristol-Myers Squibb, Abbott Japan, Eisai, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Daiichi-Sankyo, Yakult, Otsuka Pharmaceutical, Nobelpharma; Consulting or advisory role: Nano Carrier, Bayer Yakuhin,Eisai,Kyowa Hakko Kirin, Novartis Pharma,Shire, MSD; Research Funding (Recipient: institution): Bayer Yakuhin, Kyowa Hakko Kirin, Yakult, Taiho Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, Eisai, AstraZeneca, Zeria Pharmaceutical, Baxter, Chugai Pharmaceutical, Bristol Myers Sqiibb, Merck Serono, Kowa, Nano Carrier, ASLAN Pharmaceuticals T. Okusaka: Membership on an advisory board or board of directors: Dainippon Sumitomo Pharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd. , Daiichi Sankyo Co., Ltd.; Corporate-sponsored research: Eli Lilly Japan K.K., Eisai Co., Ltd., Novartis Pharma K.K., Yakult Honsha Co., Ltd., Taiho Pharmaceutical Co., Ltd., Kowa Company, LTD, Kyowa Hakko Kirin Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Pfizer Japan Inc., AstraZeneca K.K., Dainippon Sumitomo Pharma Co., Ltd., Nano Carrier Co., Ltd., Baxter, Chugai Pharmaceutical Co., Ltd. J. Furuse: Honoraria: Taiho, Chugai, Yakult, Sumitomo Dainippon, Eli Lilly Japan, Astellas, Ono, Pfizer, Bayer, Novartis, Merck Serono, Takeda, Eisai, MSD, Shionogi, J-Pharma, Daiichi Sankyo, Mochida, Nippon Kayaku, EA pharma, Sawai, Teijin Pharma; Consulting or advisory role: Taiho, Chugai, Yakult, Sumitomo Dainippon, Eli Lilly Japan, Astellas, Ono, Pfizer, Bayer, Novartis, Merck Serono, Takeda, Eisai, MSD, Shionogi, J-Pharma, Daiichi Sankyo, Kyowa Hakko Kirin, Sanofy, Sandoz, Otsuka, Zeria, Fujifilm, Astra Zeneca, Asahi Kasei, Shire; Research funding (Recipient: institution): J-Pharma, Taiho, Sumitomo Dainippon, Janssen, Daiichi Sankyo, MSD, Yakult, Takeda, Chugai, Ono, Astellas, Zeria, Novartis, Nanocarrier, Shionogi, Onco Therapy Science, Eli Lilly Japan, Bayer, Bristol-Myers Squibb, Merck Serono, Kyowa Hakko Kirin, Eisai, NanoCarrier, Mochida, Baxalta, Sanofi. All other authors have declared no conflicts of interest.