LBA31 - Randomized phase III trial of maintenance chemotherapy with tegafur-uracil versus observation following concurrent chemoradiotherapy for locally advanced cervical cancer, GOTIC-002 LUFT trial

Background

Maintenance chemotherapy with oral tegafur-uracil (UFT) after surgery was shown to prolong survival in lung, breast, gastric and colon cancer. Aim of this trial is to elucidate the efficacy of maintenance chemotherapy using UFT following concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer.

Methods

Eligible patients (pts) are those with FIGO (2008) stage Ib2 -IVa cervical cancer, who have squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma. Pts must have completed curative treatment of CCRT with a response of CR or PR. Pts were randomized to observation only (Arm O) or UFT maintenance cohort (Arm UFT) with 1:1 ratio. Dose of oral UFT was 400 mg /day for pts with body surface area (BSA)≥ 1.25 m² and 300 mg/day for pts with BSA < 1.25 m². Pts received UFT for 2 years without interruption unless disease progression or unacceptable toxicities happened. Primary endpoint was PFS and secondary endpoints included OS, safety and QOL. Significant level was 0.05 (one-side).

Results

Enrollment started in 2010 and completed in 2018. A total of 351 pts from 55 institutions in Japan were randomized either to Arm O (178 pts) or Arm UFT (173 pts). Safety data was analyzed in 176 pts in Arm O and 168 pts in Arm UFT. Pts characteristics were well balanced between two arms. Most of pts were stage IIb or IIIb, and received CCRT using weekly cisplatin. Median PFS did not reach for both arms. Five-year PFS rates were 61.3% (90%CI: 54.8-67.1) for Arm O and 62.0% (90%CI: 55.4-67.8) for Arm UFT (p=0.634). Hazard ratio (HR) of PFS for Arm UFT vs. Arm O was 0.92 (90%CI: 0.69-1.22). Five-year OS rates were 77.6% (90%CI: 71.8-82.4) for Arm O and 76.1% (90%CI: 70.1-81.1) for Arm UFT (p=0.869). HR of OS for Arm UFT vs. Arm O was 1.04 (90%CI: 0.73-1.47). All grade adverse events (AEs) occurred significantly more in Arm UFT (93.5%) than Arm O (73.9%) (Odds ratio = 5.05, 95%CI: 2.51, 10.15) but most of them were grade 1 or 2. Incidence of AEs ≥ grade 3 were 15.9% in Arm O and 22.6% in Arm UFT.

Conclusions

Maintenance chemotherapy using UFT for 2 years after definitive chemoradiation therapy for locally advanced cervical cancer was well tolerated. However, it did not improve either PFS or OS.

Clinical trial identification

jRCTs031180174.

Editorial acknowledgement

Legal entity responsible for the study

Gynecologic Oncology Trial and Investigation Consortium (GOTIC).

Funding

Taiho Pharmaceutical CO., Ltd.

Disclosure

K. Fujiwara: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Takeda, Regenerone, Zeria; Financial Interests, Personal, Advisory Board: MSD, Eisai, Genmab, Nano Carrier, Daiichi Sankyo; Financial Interests, Institutional, Funding: Regenerone; Financial Interests, Institutional, Research Grant: MSD, Ono, Zeria, Genmab; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Leadership Role: GOTIC. K. Hasegawa: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Takeda, Chugai, Genmab, Kaken, Eisai; Financial Interests, Institutional, Funding, contracted research: MSD, Ono, Daiichi Sankyo, Eisai. All other authors have declared no conflicts of interest.