Abstract | PURPOSE: METHODS: We performed a single-center retrospective cohort analysis of patients who received anti-PD1±anti-CTLA4 ICI for advanced melanoma between 2012 and 2019. Primary tumor type, BRAF and NRAS mutation status, and other covariates were abstracted from chart review. Log-rank tests and multivariable Cox regression models were used to assess differences in clinical progression-free (cPFS) and overall survival (OS). RESULTS: We identified 230 patients who received 249 lines of anti-PD1±anti-CTLA4 ICI for unresectable or metastatic disease. Of these patients, 74% were cutaneous, 11% mucosal, 8% unknown primary and 7% acral. BRAF and NRAS mutations were identified in 35% and 28% of patients, respectively. In multivariable analyses of the entire cohort, acral or mucosal primary tumor type, >3 metastatic sites, elevated LDH were predictive of shorter cPFS and OS. Combination ICI therapy was associated with longer cPFS (HR 0.57, 95% CI 0.38 to 0.86, p=0.007) and OS (HR 0.42, 95% CI 0.28 to 0.65, p<0.001). Combination ICI was significantly associated with longer OS in unknown primary and mucosal melanoma. There was a non-significant trend toward longer OS with anti-PD1+anti-CTLA4 in cutaneous melanoma, but not in acral melanoma. In multivariable analyses, combination ICI was associated with longer OS in NRAS (HR 0.24, 95% CI 0.10 to 0.62, p=0.003, n=69) and BRAF V600E/K (HR 0.47, 95% CI 0.24 to 0.90, p=0.024, n=86) mutant melanoma but not BRAF/NRAS wild-type (n=94) melanoma. CONCLUSIONS: In our cohort, primary melanoma tumor type and genomic subtype were independent predictive markers of cPFS and OS for patients with metastatic melanoma receiving anti-PD1 ICI. Primary tumor type and genomic subtype-including NRAS-should be further evaluated in prospective clinical trials to determine their value as predictive markers. Biologic subtypes may facilitate clinical decision-making when recommending combination ICI treatment (anti-PD1±anti-CTLA4) versus anti-PD1 alone for patients with metastatic melanoma.
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Authors | April A N Rose, Susan M Armstrong, David Hogg, Marcus O Butler, Samuel D Saibil, Diana P Arteaga, Thiago Pimentel Muniz, Deirdre Kelly, Danny Ghazarian, Ian King, Zaid Saeed Kamil, Kendra Ross, Anna Spreafico |
Journal | Journal for immunotherapy of cancer
(J Immunother Cancer)
Vol. 9
Issue 1
(01 2021)
ISSN: 2051-1426 [Electronic] England |
PMID | 33483342
(Publication Type: Clinical Study, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. |
Chemical References |
- Immune Checkpoint Inhibitors
- Ipilimumab
- Membrane Proteins
- Nivolumab
- BRAF protein, human
- Proto-Oncogene Proteins B-raf
- GTP Phosphohydrolases
- NRAS protein, human
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Topics |
- Drug Synergism
- Female
- GTP Phosphohydrolases
(genetics)
- Humans
- Immune Checkpoint Inhibitors
(administration & dosage, pharmacology)
- Ipilimumab
(administration & dosage, pharmacology)
- Male
- Melanoma
(classification, drug therapy, genetics)
- Membrane Proteins
(genetics)
- Mutation
- Neoplasm Metastasis
- Nivolumab
(administration & dosage, pharmacology)
- Proto-Oncogene Proteins B-raf
(genetics)
- Retrospective Studies
- Survival Analysis
- Treatment Outcome
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