Correction: PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability

Some adult patients with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) small bowel adenocarcinoma might benefit from pembrolizumab in controlling the disease (i.e., some patients achieved a partial or complete response after treatment). These findings are based on 2 single-arm studies (i.e., no comparator) with fewer than 20 patients in each study, which limits the certainty of the findings. The longer-term benefit of pembrolizumab is unclear, as some outcomes (e.g., progression-free survival, overall survival) were not reached at the time of data analysis. The safety of pembrolizumab in patients with MSI-H/dMMR small bowel adenocarcinoma is unknown (no evidence was found for this population). No evidence was identified regarding the clinical effectiveness of pembrolizumab monotherapy for patients with MSI-H/dMMR appendiceal adenocarcinoma. No evidence was identified regarding the cost-effectiveness of pembrolizumab monotherapy for patients with MSI-H/dMMR small bowel adenocarcinoma or appendiceal adenocarcinoma. No evidence-based guidelines were identified regarding pembrolizumab monotherapy for patients with MSI-H/dMMR appendiceal adenocarcinoma. One guideline was identified that recommends pembrolizumab as an option for initial or subsequent therapy in patients with advanced or metastatic MSI-H/dMMR small bowel adenocarcinoma.

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Microsatellite instability and mutations in BRAF and KRAS in small bowel adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15037 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15037-e15037

Author(s):

Vasiliki Michalaki ◽

Andreas Polydorou ◽

Theodosios Theodosopoulos ◽

George Frangulidis ◽

Nikolaos Dafnios ◽

...

Keyword(s):

Overall Survival ◽

Small Bowel ◽

Microsatellite Instability ◽

Small Bowel Adenocarcinoma ◽

Targeted Agents ◽

First Line ◽

Braf Mutations ◽

Platinum Based Chemotherapy ◽

Molecular Targeted Agents ◽

Line Chemotherapy

e15037 Background: Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. Activating KRAS and/or BRAF mutations have been identified as predictors of resistance to anti-epidermal growth factor receptor (EGFR) The aim of this study was to perform a comprehensive immunohistochemical.analysis of KRAS, NRAS, V600E BRAF mutations and microsatellite instability using a cohort of surgically resected cases in our institution. Methods: A total of 17 patients (10 males and 7 females; mean age, 56.2 years old; range, 45-75 years old) received chemotherapy due to non-curative tumor resection, unresectable tumor or post-operative recurrence. Twelve patents received fluoropirimidine and oxaliplatin based first line chemotherapy. Molecular targeted agents were administered to 15 patients, for whom it was their first- or second-line therapy. Results: KRAS mutations were found in 7 cases (41%), out of which 5 (29%) were in exons 12/13. BRAFV600E mutation was observed in 1/17 pt. Microsatellite instability was identified in 3/17pt (MSI; 18%), mainly related to a loss of expression of MLH1 protein. Univariate analysis revealed a PS of 0 (P=0.0226) and treatment with platinum-based chemotherapy (P=0.0047) were significant factors for an improved prognosis. Among the 12 patients who received oxaliplatin-based chemotherapy as a first-line chemotherapy, a PS of 0 (P=0.0255) and treatment with anti-EGFR agents (P=0.0127) were significant positive prognostic factors. Toxicities due to the molecular targeted agents were not experienced. The median overall survival time was 14.3 months (range, 3-52 months), the median DFS was 14.2 months and the median OS was 32 months. Conclusions: To date, there is no standard chemotherapy regimen for advanced SBAs and little is known about their molecular characteristics. The results of the present study indicate that oxaliplatin based chemotherapy containing molecular targeted agents is a well-tolerated and effective treatment option for SBA. A better understanding of disease biology may help to identify therapeutic targets and advance precision medicine.

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