CHICAGO—Data from the BAYPAN study presented at the American College of Clinical Oncology’s 2011 Annual Meeting did not support the addition of sorafenib to gemcitabine therapy in the treatment of advanced pancreatic cancer (APC). Anthony Goncalves, MD, of the Institut Paoli-Calmettes, Marseilles, France, and colleagues noted that this is in contrast to an earlier Phase I study1 that demonstrated that the gemcitabine (G) + sorafenib (S) combination was well tolerated and had activity in APC patients.
Patient criteria for eligibility include age >18 years, a diagnosis of locally advanced or metastatic pancreatic adenocarcinoma, no previous first-line treatment for advanced disease, measurable disease according to RECIST 1.0, and ECOG PS 0–2. The primary endpoint of this Phase 3 multicenter, randomized, double-blind, placebo-controlled trial was progression-free survival (PFS). The study sought to evaluate the benefit of adding sorafenib to gemcitabine therapy as first-line treatment of APC. The statistical hypothesis was an increase of median PFS from 3 to 6 months, with alpha and beta risks of 0.05 and 0.2 (power=80%), respectively, and required 104 patients to be enrolled. Secondary endpoints were best objective response rate, overall survival, safety, and quality of life.
Patients received gemcitabine 1,000mg/m2 IV weekly for seven weeks followed by one week of rest; then weekly for 3 weeks followed by one week of rest for 2 cycles. Sorafenib 400mg (GS) or placebo (GP), was administered twice daily, continuously for a maximum of three cycles. Patients were continued on sorafenib or placebo alone if disease did not progress after 24 weeks. Patients were stratified by center of inclusion, age (<70 or >70 years) and extent of disease (locally advanced or metastatic). Between December 2006 and September 2009, 104 patients were enrolled (52 patients in each group).
Median age (years) of both treatment groups (GS/GP) was 64/61, respectively, and the male to female ratio for both treatment groups was 30/22 and 32/20, and the percentage of patients in each group with either metastatic or locally advanced pancreatic cancer was 77% and 23% and 83% and 17%, respectively. As of July 16, 2010, 98 patients (48/50; GS/GP) have progressed and 86 (43/43; GS/GP) have died. There was no significant difference in median PFS (GP=5.6 mos. [3.4–7.6] vs. GS=3.8 mos. [3–6]; P=0.601, log-rank test). Median overall survival rates were also similar (GP=9.2 mos. [7.7–12.9] vs. GS=8.5 mos. [6–11.1]; p=0.146, log-rank test).
The most common reported grade 3/4 adverse events (AEs) that occurred more frequently in the GS arm included skin toxicity (18%) and alopecia (10%);I P<0.001. Of the Grade 3/4 AEs, anemia occurred in more patients treated with GP (15% vs. 2; P<0.05).
Dr. Goncalves et al concluded that the addition of sorafenib to gemcitabine does not improve progression-free survival, response rate, or overall survival in patients with advanced pancreatic cancer.
1. Siu LL, Awada A, Takimoto CH, Piccart M, Schwartz B, Giannaris T et al. Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer. Clin Cancer Res. 2006 Jan 1;12(1):144-51.