Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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Genomes of tumors that are deficient in DNA mismatch repair (dMMR) have high microsatellite instability (MSI-H) and harbor hundreds to thousands of somatic mutations that encode potential neoantigens. Such tumors are therefore likely to be immunogenic, triggering upregulation of immune checkpoint proteins. Pembrolizumab, an anti‒programmed death-1 monoclonal antibody, has antitumor activity against MSI-H/dMMR cancer. We report data from the phase II KEYNOTE-158 study of pembrolizumab in patients with previously treated, advanced noncolorectal MSI-H/dMMR cancer. ⋯ Our study demonstrates the clinical benefit of anti-programmed death-1 therapy with pembrolizumab among patients with previously treated unresectable or metastatic MSI-H/dMMR noncolorectal cancer. Toxicity was consistent with previous experience of pembrolizumab monotherapy.
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Survivors of hereditary retinoblastoma have excellent survival but substantially increased risks of subsequent bone and soft-tissue sarcomas, particularly after radiotherapy. Comprehensive investigation of sarcoma risk patterns would inform clinical surveillance for survivors. ⋯ Strikingly elevated bone and soft-tissue sarcoma risks differ by age, location, and sex, highlighting important contributions of both radiotherapy and genetic susceptibility. These data provide guidance for the development of a risk-based screening protocol that focuses on the highest sarcoma risks by age, location, and sex.
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This study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer. ⋯ Patients who were treated with niraparib compared with RS experienced increased mean TWiST. Thus, patients who were treated with niraparib in the ENGOT-OV16/NOVA trial experienced more time without symptoms or symptomatic toxicities compared with control.
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Randomized Controlled Trial Multicenter Study
Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial.
We evaluated the role of oxaliplatin as adjuvant chemotherapy in patients with rectal cancer who received preoperative chemoradiotherapy (CRT) with fluoropyrimidine monotherapy and total mesorectal excision (TME). ⋯ Adjuvant FOLFOX improved DFS in patients with rectal cancer with ypStage II and III disease after preoperative CRT. Adjuvant FOLFOX may be considered on the basis of the postoperative pathologic stage in those who received preoperative CRT and TME.
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Randomized Controlled Trial Multicenter Study
Negative Hyperselection of Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer Who Received Panitumumab-Based Maintenance Therapy.
We assessed the prognostic/predictive role of primary tumor sidedness and uncommon alterations of anti-epidermal growth factor receptor (EGFR) primary resistance (primary resistance in RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies [PRESSING] panel) in patients with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) who were randomly assigned to panitumumab plus fluorouracil, leucovorin, and oxaliplatin (FOLFOX-4) induction followed by maintenance with panitumumab with or without fluorouracil (FU) plus leucovorin (LV); Valentino trial (ClinicalTrials.gov identifier: NCT02476045). ⋯ The combined assessment of sidedness and molecular alterations of anti-EGFR primary resistance identified a consistent proportion of patients with RAS/BRAF-wt mCRC who had inferior benefit from initial anti-EGFR-based regimens, particularly after maintenance with single-agent anti-EGFRs.