Phase II trial of S-1 plus cisplatin combined with bevacizumab for advanced non-squamous non-small cell lung cancer (TCOG LC-1202)

Background

S-1 plus Cisplatin is a standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC) (Ann Oncol. 2015; 26:1401-8). Bevacizumab significantly improved overall survival (OS) in patients with advanced non-squamous (NSq) NSCLC who received carboplatin plus paclitaxel, however failed to show OS advantage in patients who received cisplatin plus gemcitabine. Few studies of bevacizumab evaluated quality of life (QOL) in patients with NSq-NSCLC.

Methods

Chemotherapy-naïve patients with stage IIIB, IV, or recurrent NSq-NSCLC, ECOG PS 0-1, age 20-74 years old, and measurable lesions were treated with a 3-week cycle of S-1 40 mg/m² twice a day on days 1-14, cisplatin 60 mg/m² on day 8 and bevacizumab 15 mg/kg on day 8 for 4-6 cycles. Patients without progressive disease received maintenance bevacizumab 15 mg/kg on day 1 with a 3-week cycle and S-1 40 mg/m² twice a day on every other day. Primary endpoint was progression-free survival (PFS) and secondary endpoints were objective response (OR), OS, toxicity profile and QOL.

Results

From June 2013 to January 2015, 39 evaluable patients were enrolled from 8 institutions. Patient characteristics were: Male/Female 29/10; median age 65 years old (range 38-74); Performance status 0/1 22/17; IIIB/IV/recurrence 1/35/3; adeno/large cell/other 35/1/3. 31 patients (80%) completed 4 cycles of induction chemotherapy and 23 patients (59%) started maintenance chemotherapy. Median PFS, OS and OR were 7.3 months, 21.4 months and 64%, respectively. Worst hematologic and non-hematologic toxicities (%): grade 3/4 leukopenia (13/0); neutropenia (18/5); thrombocytopenia (0/0); anemia (0/0); neutropenic fever (3/0); hypertension (28/0); diarrhea (3/0).

Conclusions

The trial met the primary endpoint. S-1 plus cisplatin combined with bevacizumab is well tolerated and highly active in patients with advanced NSq-NSCLC. QOL data will be presented at the meeting.

Clinical trial identification

UMIN000009476

Legal entity responsible for the study

N/A

Funding

The Tokyo Cooperative Oncology Group (TCOG)

Disclosure

K. Kubota: Honoraria from Taiho, Chugai, Eli-Lilly, Daiichi-Sankyo.

Y. Hosomi: Speaker Fees as honoraria from Chugai, Eli Lilly Japan, AstraZeneca, Taiho and Ono, outside the submitted work.

Y. Takiguchi: Lecture fee from Taiho pharmaceutical co., and Chugai Pharmaceutical Co.

H. Okamoto: Corporate-sponsored research: Takeda, MSD, Ono, Astrazeneca, Merck, Chugai, Taiho, Bristol, Eli Lilly, Parexel.

All other authors have declared no conflicts of interest.