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PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma. | LitMetric

AI Article Synopsis

  • Combining anti-PD-L1 therapy (durvalumab) with MAPK inhibitors (dabrafenib and trametinib) shows potential for lasting responses in advanced melanoma patients.
  • A clinical study examined the safety and efficacy of these combinations in patients with BRAF-mutated and BRAF-wild type melanoma.
  • Results indicated higher adverse events than expected, but also significant objective response rates: 69.2% for BRAF-mutated patients and varying rates for BRAF-wild type patients, suggesting this combination approach may enhance treatment options for advanced melanoma.

Article Abstract

Combining PD-L1 blockade with inhibition of oncogenic mitogen-activated protein kinase (MAPK) signaling may result in long-lasting responses in patients with advanced melanoma. This phase 1, open-label, dose-escalation and -expansion study (NCT02027961) investigated safety, tolerability and preliminary efficacy of durvalumab (anti-PD-L1) combined with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for patients with BRAF-mutated melanoma (cohort A, n = 26), or durvalumab and trametinib given concomitantly (cohort B, n = 20) or sequentially (cohort C, n = 22) for patients with BRAF-wild type melanoma. Adverse events and treatment discontinuation rates were more common than previously reported for these agents given as monotherapy. Objective responses were observed in 69.2% (cohort A), 20.0% (cohort B) and 31.8% (cohort C) of patients, with evidence of improved tumor immune infiltration and durable responses in a subset of patients with available biopsy samples. In conclusion, combined MAPK inhibition and anti-PD-L1 therapy may provide treatment options for patients with advanced melanoma.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721806PMC
http://dx.doi.org/10.1038/s41467-020-19810-wDOI Listing

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