Objective: Since 2010, gemcitabine and cisplatin have been considered standard first-line treatment in patients with advanced biliary tract cancer. Many centers have replaced cisplatin with oxaliplatin, which seems to obtain similar results. While first-line treatment has been well established, there are no phase III trials supporting second-line treatment, and the phase II trials with chemotherapy do not show any clear benefit. In this study, we investigated the effect of adding bevacizumab to chemotherapy in second-line treatment. Methods: From November 2013 to January 2016, 50 patients with advanced biliary tract cancer were enrolled in this prospective phase II trial. All patients had received a gemcitabine-platinum combination as first-line treatment. The patients received capecitabine, irinotecan, gemcitabine, and bevacizumab in a 2-week schedule as second-line treatment. Results: The combination was well tolerated with a median progression-free survival of 3.6 months, a median overall survival of 6.4 months, and a response rate of 6%. Conclusion: The combination of capecitabine, irinotecan, gemcitabine, and bevacizumab as a second-line treatment for advanced biliary tract cancer is well tolerated but with a modest, if any, benefit.

This study is an investigator-initiated randomized phase II trial focusing on the treatment of advanced biliary tract cancer with either oxaliplatin 50 mg/m2 and gemcitabine 1000 mg/m2 on day 1 in a two-week cycle with capecitabine 650 mg/m2 twice-daily continuously or cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and day 8 in a three-week cycle. One-hundred patients were included. Forty-seven patients received oxaliplatin, gemcitabine, and capecitabine with a median progression-free survival (mPFS) of 5.7 months (95% CI 3.0–7.8) and a median overall survival (mOS) of 8.7 months (95% CI 6.5–11.2). Forty-nine patients received cisplatin and gemcitabine with a mPFS of 7.3 months (95% CI 6.0–8.7) and a mOS of 12.0 months (95% CI 8.3–16.7). This trial confirms a mOS of 12 months with cisplatin and gemcitabine, as found in earlier trials. With a superior tumor control rate of 79% vs. 60% (p = 0.045), a difference in the mPFS of 1.6 months (HR = 0.721, p = 0.1), and a difference in the mOS of 3.3 months (HR = 0.731, p = 0.1), cisplatin and gemcitabine should still be considered the standard first-line treatment for advanced biliary tract cancer.

LBA3503 Background: Locally advanced colon cancer presents a therapeutic challenge regarding improving survival and minimizing side effects by optimizing the timing of surgical and systemic treatments. Neoadjuvant chemotherapy is a widely accepted approach in numerous cancers as it aims to eliminate micrometastases and reduce tumor size. Our study aimed to assess the impact of neoadjuvant chemotherapy on locally advanced colon cancer compared to standard initial surgery. Methods: This was a randomized, controlled, phase III clinical trial. Patients aged 18 years or older with biopsy-proven colon cancer were eligible for inclusion if staged as T4 or T3 with invasion depth ≥5 mm, N0-2, and M0 according to CT scan evaluation. Patients were randomly assigned to either standard upfront surgery or surgery after neoadjuvant chemotherapy with either 3 cycles of CAPOX (oxaliplatin, capecitabine every 3 weeks) or 4 cycles of FOLFOX (oxaliplatin, 5FU every 2 weeks). Adjuvant chemotherapy was chosen based on the pathological stage of the cancer according to guidelines. The primary endpoint, disease-free survival (DFS), was analyzed on an intent-to-treat basis. The sample size was set at 125 patients per arm, based on a projected increase in two-year disease-free survival from 80% to 90%, with a two-sided significance level of 5%, power of 80%, 3 years of inclusion, 2 years of follow-up, and a 10% drop-out rate. Results: Nine centers in 3 countries included 122 patients in the standard group and 126 patients in the neoadjuvant group from 10/2013 to 11/2021. Forty-four % were female, the median age was 66 years, and 91% had a performance status (PS) of 0, while 9% had a PS of 1. Seventy-three % of the tumors were classified as T3, with a median outgrowth of 11 mm, while 26% were classified as T4 on the baseline CT scan. There were no significant differences in baseline characteristics. The median number of chemotherapy cycles was lower in the neoadjuvant group, 3 (IQR 1-7) vs. 4 (0-8). There were slightly more postoperative complications in the standard group regarding ileus, anastomotic leakage, and length of stay. Postoperatively, more patients in the standard arm had an indication of adjuvant chemotherapy, 88 vs. 72 (p = 0.02). DFS at 2 years was similar in the two arms (p = 0.95, logrank), as was overall survival (OS) (p = 0.95, logrank). Conclusions: Neoadjuvant chemotherapy and standard upfront surgery showed no significant difference in DFS and OS in patients with colon cancer. However, neoadjuvant chemotherapy seemed to have more favorable outcomes in terms of chemotherapy cycles, postoperative complications, and downstaging. CT scan alone may not be sufficient in identifying high-risk patients preoperatively. These findings suggest that neoadjuvant chemotherapy could be considered a viable treatment option for patients with locally advanced colon cancer. Clinical trial information: NCT01918527 .