Treatment efficacy of ramucirumab-containing chemotherapy in patients with alpha-fetoprotein producing gastric cancer

International Journal of Clinical Oncology - Alpha-Fetoprotein Producing Gastric Cancer (AFPGC) is an aggressive subgroup of gastric cancer. Recently ramucirumab has shown survival benefits in...     

Perioperative TAS-118 plus oxaliplatin in patients with locally advanced gastric cancer: APOLLO-11 study

Background

We investigated the feasibility of perioperative chemotherapy with S-1 and leucovorin (TAS-118) plus oxaliplatin in patients with locally advanced gastric cancer.

Methods

Patients with clinical T3–4N1–3M0 gastric cancer received four courses of TAS-118 (40–60 mg/body, orally, twice daily for seven days) plus oxaliplatin (85 mg/m², intravenously, day one) every two weeks preoperatively followed by gastrectomy with D2 lymphadenectomy, followed by postoperative chemotherapy with either 12 courses of TAS-118 monotherapy (Step 1) or eight courses of TAS-118 plus oxaliplatin (Step 2). The primary endpoints were completion rates of preoperative chemotherapy with TAS-118 plus oxaliplatin and postoperative chemotherapy with TAS-118 monotherapy (Step 1) or TAS-118 plus oxaliplatin (Step 2).

Results

Among 45 patients enrolled, the preoperative chemotherapy completion rate was 88.9% (90% CI 78.0–95.5). Major grade ≥ 3 adverse events (AEs) were diarrhoea (17.8%) and neutropenia (8.9%). The R0 resection rate was 95.6% (90% CI 86.7–99.2). Complete pathological response was achieved in 6 patients (13.3%). Dose-limiting toxicity was not observed in 31 patients receiving postoperative chemotherapy (Step 1, n = 11; Step 2, n = 20), and completion rates were 90.9% (95% CI 63.6–99.5) for Step 1 and 80.0% (95% CI 59.9–92.9) for Step 2. No more than 10% of grade ≥ 3 AEs were observed in  patients receiving Step 1. Hypokalaemia and neutropenia occurred in 3 and 2 patients, respectively, receiving Step 2. The 3-year recurrence-free and overall survival rates were 66.7% (95% CI 50.9–78.4) and 84.4% (95% CI 70.1–92.3), respectively.

Conclusions

Perioperative chemotherapy with TAS-118 plus oxaliplatin with D2 gastrectomy is feasible.

     

Encorafenib,binimetinib, and cetuximab in BRAF V600E–mutated colorectal cancer: an early post-marketing phase vigilance study

Background

Triplet and doublet regimens of encorafenib plus cetuximab with and without binimetinib, respectively, were approved in Japan for unresectable, metastatic, BRAF V600E-mutated colorectal cancer (mCRC) that had progressed after 1–2 prior chemotherapies. This early post-marketing phase vigilance (EPPV) study collected adverse drug reactions (ADRs) from Japanese patients to ensure safety measures as appropriate.

Methods

Patients with BRAF V600E mCRC who received the triplet or doublet regimens in Japan were selected for this study. ADRs were collected as spontaneous reports between November 27, 2020 and May 26, 2021. Serious ADRs were evaluated according to guidelines of the International Council for Harmonisation and the EudraVigilance list of Important Medical Event Terms.

Results

An estimated 550 Japanese patients with mCRC received the triplet or doublet regimens during the 6-month EPPV period. Overall, 101 and 42 patients reported ADRs and serious ADRs, respectively. No ADRs leading to death were reported. The most frequently reported ADRs were nausea (17 patients), serous retinal detachment (16), decreased appetite (12), diarrhea (11), and vomiting (11). Among the important identified/potential risks that are defined in the risk management plans for encorafenib and binimetinib, eye disorder-related ADRs were observed in 32 patients, rhabdomyolysis-related ADRs in 12, hemorrhage-related ADRs in 7, and hepatic dysfunction-related ADRs in 7. Of 22 patients with serious eye disorders, 20 recovered or were recovering during the EPPV period.

Conclusion

The safety profile in this EPPV study was similar to that from the phase III BEACON CRC study and no new safety concerns were identified.