Clinical Outcomes and Longitudinal Circulating Tumor DNA Changes After Treatment with Nivolumab and Olaparib in Immunotherapy Relapsed Melanoma with Detected Homologous Recombination Deficiency

Overview

Journal Cold Spring Harb Mol Case Stud

Specialty Genetics

Date 2021 Oct 20

PMID 34667064

Citations 6

Authors

Karam Khaddour

Michael Ansstas

George Ansstas

Affiliations

Soon will be listed here.

Abstract

The treatment of immunotherapy relapsed cutaneous melanoma constitutes a challenge in both research and clinical practice fields given the lack of effective therapeutic options. Homologous recombination deficiency (HRD) has been identified in several solid cancers including cutaneous melanoma. However, the utility of medications targeting HRD cancer cells is an uncharted territory in melanoma. Moreover, preclinical evidence suggests a synergistic role of combining immune checkpoint blockade (ICB) with drugs targeting HRD cancer cells such as PARP inhibitors. Here, we present a case study of a patient with immunotherapy relapsed melanoma who was found to have detected HRD and was treated with nivolumab (ICB) and olaparib (PARP inhibitors).

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References

Li A, Yi M, Qin S, Chu Q, Luo S, Wu K . Prospects for combining immune checkpoint blockade with PARP inhibition. J Hematol Oncol. 2019; 12(1):98. PMC: 6744711. DOI: 10.1186/s13045-019-0784-8. View

Beaubier N, Tell R, Lau D, Parsons J, Bush S, Perera J . Clinical validation of the tempus xT next-generation targeted oncology sequencing assay. Oncotarget. 2019; 10(24):2384-2396. PMC: 6481324. DOI: 10.18632/oncotarget.26797. View

Ray-Coquard I, Pautier P, Pignata S, Perol D, Gonzalez-Martin A, Berger R . Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019; 381(25):2416-2428. DOI: 10.1056/NEJMoa1911361. View

Knijnenburg T, Wang L, Zimmermann M, Chambwe N, Gao G, Cherniack A . Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas. Cell Rep. 2018; 23(1):239-254.e6. PMC: 5961503. DOI: 10.1016/j.celrep.2018.03.076. View

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob J, Rutkowski P, Lao C . Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2019; 381(16):1535-1546. DOI: 10.1056/NEJMoa1910836. View

Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz L, Mandrekar S . iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017; 18(3):e143-e152. PMC: 5648544. DOI: 10.1016/S1470-2045(17)30074-8. View

Khaddour K, Ansstas M, Visconti J, Ansstas G . Mutation clearance and complete radiologic resolution of immunotherapy relapsed metastatic melanoma after treatment with nivolumab and olaparib in a patient with homologous recombinant deficiency: any role for PARP inhibitors and checkpoint blockade?. Ann Oncol. 2020; 32(2):279-280. DOI: 10.1016/j.annonc.2020.10.602. View

Teo M, Seier K, Ostrovnaya I, Regazzi A, Kania B, Moran M . Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers. J Clin Oncol. 2018; 36(17):1685-1694. PMC: 6366295. DOI: 10.1200/JCO.2017.75.7740. View

Pilie P, Tang C, Mills G, Yap T . State-of-the-art strategies for targeting the DNA damage response in cancer. Nat Rev Clin Oncol. 2018; 16(2):81-104. PMC: 8327299. DOI: 10.1038/s41571-018-0114-z. View

10.

Kim K, Soroceanu L, de Semir D, Millis S, Ross J, Vosoughi E . Prevalence of Homologous Recombination Pathway Gene Mutations in Melanoma: Rationale for a New Targeted Therapeutic Approach. J Invest Dermatol. 2021; 141(8):2028-2036.e2. DOI: 10.1016/j.jid.2021.01.024. View

11.

Heeke A, Pishvaian M, Lynce F, Xiu J, Brody J, Chen W . Prevalence of Homologous Recombination-Related Gene Mutations Across Multiple Cancer Types. JCO Precis Oncol. 2018; 2018. PMC: 6139373. DOI: 10.1200/PO.17.00286. View

12.

Lanman R, Mortimer S, Zill O, Sebisanovic D, Lopez R, Blau S . Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA. PLoS One. 2015; 10(10):e0140712. PMC: 4608804. DOI: 10.1371/journal.pone.0140712. View

13.

Sahnane N, Carnevali I, Formenti G, Casarin J, Facchi S, Bombelli R . BRCA Methylation Testing Identifies a Subset of Ovarian Carcinomas without Germline Variants That Can Benefit from PARP Inhibitor. Int J Mol Sci. 2020; 21(24). PMC: 7767143. DOI: 10.3390/ijms21249708. View

14.

Lau B, Menzies A, Joshua A . Ongoing partial response at 6 months to olaparib for metastatic melanoma with somatic PALB2 mutation after failure of immunotherapy: a case report. Ann Oncol. 2020; 32(2):280-282. DOI: 10.1016/j.annonc.2020.11.006. View

15.

Nishino M, Hatabu H, Hodi F . Imaging of Cancer Immunotherapy: Current Approaches and Future Directions. Radiology. 2018; 290(1):9-22. PMC: 6312436. DOI: 10.1148/radiol.2018181349. View

16.

Kakoti S, Sato H, Laskar S, Yasuhara T, Shibata A . DNA Repair and Signaling in Immune-Related Cancer Therapy. Front Mol Biosci. 2020; 7:205. PMC: 7506057. DOI: 10.3389/fmolb.2020.00205. View

17.

Chabanon R, Muirhead G, Krastev D, Adam J, Morel D, Garrido M . PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer. J Clin Invest. 2018; 129(3):1211-1228. PMC: 6391116. DOI: 10.1172/JCI123319. View

18.

Hamid O, Robert C, Daud A, Hodi F, Hwu W, Kefford R . Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Ann Oncol. 2019; 30(4):582-588. PMC: 6503622. DOI: 10.1093/annonc/mdz011. View

19.

Moschetta M, George A, Kaye S, Banerjee S . BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Ann Oncol. 2016; 27(8):1449-55. DOI: 10.1093/annonc/mdw142. View