Trifluridine/tipiracil with and without ramucirumab for advanced gastric cancer: a comparative observational study.

The combination of trifluridine/tipiracil hydrochloride (FTD/TPI) plus ramucirumab has demonstrated clinical activity in patients with advanced gastric cancer (AGC). We evaluated the efficacy and safety of this combination compared with those of FTD/TPI monotherapy in patients with AGC. We retrospectively reviewed data of patients with AGC who received FTD/TPI plus ramucirumab or FTD/TPI monotherapy as third- or later-line treatment. This study included 36 patients treated with FTD/TPI plus ramucirumab and 70 patients receiving FTD/TPI monotherapy. The objective response rate (ORR) and disease control rate (DCR) were 25.8% and 58.1%, respectively, in the FTD/TPI plus ramucirumab group and 5.0% and 38.3%, respectively, in the FTD/TPI group (ORR, P = 0.007; DCR, P = 0.081). The median progression-free survival (PFS) was significantly longer in the FTD/TPI plus ramucirumab group (median PFS, 2.9 vs. 1.8 months; hazard ratio [HR]: 0.52; P = 0.001). A numerical survival benefit was also observed (median overall survival, 7.9 months vs. 5.0 months; HR: 0.68, P = 0.089). In the multivariate analysis, PFS was significantly longer in the FTD/TPI plus ramucirumab group than in the FTD/TPI monotherapy group (HR: 0.61, P = 0.030). The incidence of febrile neutropenia was higher in the FTD/TPI plus ramucirumab group than in the FTD/TPI group (13.8% vs. 2.9%); however, no new safety signals were identified. Compared with FTD/TPI monotherapy, FTD/TPI plus ramucirumab offers clinical benefits with acceptable toxicity in heavily pretreated patients with AGC. Further investigation via randomized trials is warranted to confirm these findings.

Early detection of brain metastases and appropriate local therapy followed by systemic chemotherapy may improve the prognosis of gastric cancer.

Brain metastases develop in 0.5-0.7% of patients with gastric/gastroesophageal junction (G/GEJ) cancer. Although rare, brain metastasis is often identified when the patient is already symptomatic; hence prognosis is poor. Given the therapeutic developments for G/GEJ cancer, overall survival is prolonged, thereby the incidence of brain metastases is predicted to increase. We retrospectively surveyed the rate of brain metastasis among 1257 patients diagnosed with G/GEJ cancer who received chemotherapy between January 2011 and April 2021. We investigated the time of onset of brain metastasis, treatments administered, and impact of the metastasis on the overall treatment course and prognosis. Of the 741 patients included in the analysis, brain metastasis was confirmed in 16 (2.2%). The median survival time (MST) from G/GEJ cancer diagnosis was 14.9 months in patients with brain metastasis detected during the treatment period, and the MST from the diagnosis of brain metastasis was 2.8 months. Patients who received chemotherapy exhibited prolonged survival compared with those who did not (12.4 months vs 1.0 months, p < 0.001). Our findings suggest that the early detection of brain metastases and local therapy for poor responders to chemotherapy enable the continuation of chemotherapy and prolong survival.

Checkpoint inhibitor-induced gastritis followed by delayed severe hepatitis in a patient with lung metastases of head and neck squamous cell carcinoma: a case report.

Pembrolizumab, an anti-programmed death-1 (PD-1) receptor monoclonal antibody, is an effective first-line therapy for metastatic head and neck squamous cell carcinoma. Immune-related adverse events (irAEs) are well-described complications of PD-1 inhibitors, and multiorgan irAEs are known to occur occasionally. We report a patient with pulmonary metastases of oropharyngeal squamous cell carcinoma (SCC), who developed gastritis followed by delayed severe hepatitis and recovered with triple immunosuppressant therapy. A 58-year-old Japanese male with pulmonary metastases of oropharyngeal SCC who was treated with pembrolizumab, subsequently developed new-onset appetite loss and upper abdominal pain. Upper gastrointestinal endoscopy revealed gastritis and immunohistochemistry revealed pembrolizumab-induced gastritis. The patient developed delayed severe hepatitis at 15 months after initiating pembrolizumab treatment, presenting "Grade 4 aspartate aminotransferase increase" and "Grade 4 alanine aminotransferase increase." Impaired liver function persisted despite pulse corticosteroid therapy with intravenous methylprednisolone 1,000 mg/day, followed by oral prednisolone 2 mg/kg/day and oral mycophenolate mofetil 2,000 mg/day. Tacrolimus, which reached target serum trough concentrations of 8-10 ng/mL, gradually improved irAE grades from Grade 4 to Grade 1. The patient responded well to triple immunosuppressant therapy comprising prednisolone, mycophenolate mofetil, and tacrolimus. Therefore, this immunotherapeutic approach could be effective for multiorgan irAEs in patients with cancer.

TRESBIEN (OGSG 2101): encorafenib, binimetinib and cetuximab for early recurrent stage II/III BRAF V600E-mutated colorectal cancer.

The BRAF V600E mutation accounts for approximately 5% of colorectal cancer (CRC) cases and is an extremely poor prognostic factor. However, there are no clear recommendations regarding first-line therapy for patients with early recurrent BRAF V600E-mutated CRC, during or after adjuvant chemotherapy. Recently, a novel combination of encorafenib, binimetinib and cetuximab, showed a higher response rate than standard chemotherapy in patients with BRAF V600E-mutated CRC. Here we describe our plan for the TRESBIEN study (OGSG 2101), which is an open-label, multicenter, single-arm, phase II study designed to evaluate whether encorafenib, binimetinib and cetuximab are effective for patients with early recurrent BRAF V600E-mutated colorectal cancer, during or after adjuvant chemotherapy. The planned number of subjects is 25.

An ongoing study to evaluate encorafenib, binimetinib and cetuximab for people with early recurrent BRAF V600E-mutated colorectal cancer. BRAF V600E-mutated colorectal cancer (CRC) is a type of cancer caused by change (mutation) in a gene called BRAF. It is one of the most difficult types of CRC to treat because currently available drugs do not effectively treat the disease. Recently, two novel treatments, encorafenib and cetuximab, have been approved for use together in several countries for the treatment of advanced or metastatic BRAF V600E-mutated CRC. In Japan, these drugs are also approved to be given with another treatment called binimetinib, an approach called triplet therapy. This article describes the ongoing TRESBIEN study that is looking at how effective and how safe triplet therapy is for the treatment of people with early recurrent BRAF V600E-mutated CRC, during or after they have additional (adjuvant) chemotherapy. This study is ongoing, and the researchers are currently recruiting new participants. TRESBIEN will evaluate the percentage of participants whose tumors shrink with triplet therapy. The study will also look at any side effects. Clinical Trial Registration: jRCTs051210152 (ClinicalTrials.gov) (Japan Registry of Clinical Trials https://jrct.niph.go.jp/search?language=en&page=1).

Retrospective Comparison of mFOLFOXIRI With XELOX/SOX as Neoadjuvant Chemotherapy for Locally Advanced Rectal Cancer.

BACKGROUND/AIM: Neoadjuvant chemotherapy without radiation (NAC) shows favorable outcomes for locally advanced rectal cancer (LARC), however, the optimal regimen has not been determined yet. This study aimed to compare the efficacy and safety of oxaliplatin, irinotecan, folinic acid, and 5-fluorouracil (mFOLFOXIRI) with capecitabine/S-1 and oxaliplatin (XELOX/SOX) in rectal cancer patients. PATIENTS AND METHODS: We retrospectively examined patients with LARC who received mFOLFOXIRI or XELOX/SOX as NAC. RESULTS: Between January 2015 and July 2019, 49 patients received mFOLFOXIRI and 37 patients received XELOX/SOX. The pathological response rates (over two-thirds affected tumor area) were 36.7% and 40.5% in the mFOLFOXIRI and XELOX/SOX groups, respectively. Grade 3/4 neutropenia was experienced by 45.0% of the patients in the mFOLFOXIRI group and 8.0% in the XEOX/SOX group. CONCLUSION: Although pathological responses were comparable between two groups, mFOLFOXIRI tended to be more toxic compared to XELOX/SOX as NAC for LARC.