First-line atezolizumab monotherapy in patients with advanced BRAF V600 wild-type melanoma

Pigment Cell Melanoma Res. 2021 Sep;34(5):973-977. doi: 10.1111/pcmr.12960. Epub 2021 Feb 15.

Abstract

Anti-programmed death-1 agents are an established option for advanced melanoma, but the anti-programmed death-ligand 1 (anti-PD-L1) antibody atezolizumab, an agent approved for the treatment of multiple solid tumors, was not previously evaluated. This phase 1b study cohort (NCT03178851; cohort C) evaluated first-line atezolizumab 1,200 mg every 3 weeks in adults with BRAFV600 wild-type, histologically confirmed, advanced or metastatic melanoma. The co-primary end points were confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors v1.1 and disease control rate (DCR = complete response [CR] +partial response [PR] +stable disease [SD] at 16 weeks). Of 52 enrolled patients, most had lactate dehydrogenase levels lower than the upper limit of normal (77%) and PD-L1-positive tumors (55%). Investigator-assessed confirmed ORR was 35% (95% CI, 22%-49%) and included three CRs (6%) and 15 PRs (29%); DCR was 46%. Median investigator-assessed progression-free survival was 3.7 months (95% CI, 2.1-7.3). The most common any-grade adverse events were anemia (27%), headache (19%), hypertension (19%), constipation (17%), diarrhea (17%), hypothyroidism (17%), asthenia (15%), and pain in extremity (15%). First-line atezolizumab monotherapy is safe and tolerable and has antitumor activity in patients with BRAFV600 wild-type advanced or metastatic melanoma.

Trial registration: ClinicalTrials.gov NCT03273153 NCT02908672 NCT03178851.

Keywords: antibodies; atezolizumab; immunomodulation; melanoma; monoclonal antibody.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / metabolism
  • Melanoma* / mortality
  • Middle Aged
  • Progression-Free Survival
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism*
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / mortality
  • Survival Rate

Substances

  • Antibodies, Monoclonal, Humanized
  • atezolizumab
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf

Associated data

  • ClinicalTrials.gov/NCT03273153
  • ClinicalTrials.gov/NCT02908672
  • ClinicalTrials.gov/NCT03178851