Articles related to CHECKPOINT INHIBITORS

The recent 2022 ASCO GU Cancers Symposium provided important new data for the management of advanced prostate cancer. Presentations covered in this review of symposia highlights include androgen receptor (AR) inhibitors in patients with metastatic hormone-sensitive prostate cancer, combinations of PARP inhibitors with abiraterone acetate in metastatic castration-resistant prostate cancer, 177Lu-PSMA-617 in metastatic CRPC, some novel therapies, and even a look at an artificial intelligence pathology predictive biomarker.

A 12-year odyssey of a cancer drug that works in a subcellular organelle: From discovery of a unique and promising tumor target – featured on the cover of the Journal of Clinical Investigation – through startup company, grant-writing, DoD funding, Wall Street disinterest, perseverance, and finally, approval to initiate clinical trials.

According to the final results from the phase 3 PALLAS trial, palbociclib offers no benefit over endocrine therapy alone in women with early HR+ HER2- breast cancer. The primary endpoint — 4-year invasive DFS — was nearly equivalent in the test and control arms of the study. None of the secondary endpoints showed a significant difference either. There was a high rate of palbociclib discontinuation (42%), mostly due to grade 3 or 4 neutropenia. But even in those who completed the two-year planned course showed no benefit over endocrine therapy alone. The results were not just disappointing, but surprising given that CDK 4/6 inhibitors plus endocrine therapy is the standard of care for advanced breast cancer.

This single-arm study of 40 patients with advanced neuroendocrine tumors (NETs) sought to evaluate the potential benefit of a VEGF inhibitor plus a PD-L1 inhibitor. The primary endpoint was objective radiographic response. Responses were seen in 15% to 20% of patients.

The phase 3 KEYNOTE-048 trial compares pembrolizumab with or without concurrent chemotherapy to cetuximab-chemotherapy in patients with recurrent or metastatic head and neck SCC. Patients were evaluated in subgroups based on PD-L1 expression. In median survival, pembrolizumab + chemotherapy outperformed cetuximab + chemotherapy in all patient subgroups regardless of PD-L1 expression. In the PD-L1 CPS 1-19 subgroup, pembrolizumab alone slightly outperformed cetuximab + chemotherapy. In the PD-L1 CPS < 1 subgroup median survival was significantly lower with pembrolizumab alone.

Sixty patients with EGFR-amplified gastroesophageal adenocarcinoma(GEA) received EGFRi, including 31 of 60 patients (52%) with concurrent chemotherapy. Across treatment lines, patients achieved a 43% objective response rate with a median PFS of 4.6 months. Typical OS with first-line initiation of non-EGFRi therapy in patients with EGFR-amplified GEA is 11.2 months, as determined by analysis of a deidentified clinicogenomic database. Despite this benefit, analysis of that database for January 2011 through December 2020 suggests that only 5% of patients with EGFR-amplified GEA received EGFRi.