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?

Khaddour, Karam; Ansstas, Michael; Visconti, John; Ansstas, George

doi:10.1016/j.annonc.2020.10.602

Cited by 7 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Response to olaparib (PARP inhibitor) in melanoma patients has been previously reported when used as monotherapy and in combination with ICB ( Khaddour et al 2021 ; Lau et al 2021 ). The previously reported patients had high LOH scores of 28.4% and 26.5%.…”

Section: Discussion: Combination Checkpoint Inhibitors and Parp Inhibitors In The Treatment Of Melanoma With Detected Hrdmentioning

confidence: 98%

“…We previously reported radiological response and mutation clearance after treatment with nivolumab and olaparib in a patient with immunotherapy relapsed melanoma who had a high HRD score due to a germline mutation in CHEK2 and several somatic mutations in DDR genes ( Khaddour et al 2021 ). Here, we present our new observation in a 42-yr-old male with metastatic melanoma who had evidence of borderline high HRD score and was treated with nivolumab and olaparib after progression on prior ICB (nivolumab).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical outcomes and longitudinal circulating tumor DNA changes after treatment with nivolumab and olaparib in immunotherapy relapsed melanoma with detected homologous recombination deficiency

Khaddour

Ansstas

2021

Cold Spring Harb Mol Case Stud

View full text Add to dashboard Cite

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).

show abstract

Section: Discussion: Combination Checkpoint Inhibitors and Parp Inhibitors In The Treatment Of Melanoma With Detected Hrdmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Clinical outcomes and longitudinal circulating tumor DNA changes after treatment with nivolumab and olaparib in immunotherapy relapsed melanoma with detected homologous recombination deficiency

Khaddour

Ansstas

2021

Cold Spring Harb Mol Case Stud

View full text Add to dashboard Cite

show abstract

“…However, several studies have identified patients without traditional HR-DDR gene mutations that respond to PARPi therapy, underscoring the need to explore potential genetic and epigenetic markers outside of HR-DDR pathway gene mutations. 1 , 2 …”

Section: Discussionmentioning

confidence: 99%

Poly (ADP-Ribose) Polymerase inhibitors (PARPi) therapy response in an acral melanoma patient with EMSY gene amplification

Nassief,

Butt,

Zhou

et al. 2024

JAAD Case Reports

View full text Add to dashboard Cite

“…For example, Lau et al reported a PR in a melanoma patient with a PALB2 mutation who progressed during treatment with ICI and was later treated with a PARP inhibitor [ 190 ]. In contrast, two case reports suggested possible synergism between olaparib and nivolumab in two melanoma patients who were immunotherapy-refractory patients and who had evidence of HRD [ 191 , 192 ]. Of importance, one patient developed hepatitis as a side effect during combination treatment, which raises a safety concern.…”

Section: Targeting Homologous Recombination Deficiency and The Dna Damage Response Pathwaymentioning

confidence: 99%

Melanoma Targeted Therapies beyond BRAF-Mutant Melanoma: Potential Druggable Mutations and Novel Treatment Approaches

Khaddour

Maahs

Avila-Rodriguez

et al. 2021

Cancers

View full text Add to dashboard Cite

Melanomas exhibit the highest rate of somatic mutations among all different types of cancers (with the exception of BCC and SCC). The accumulation of a multimode of mutations in the driver oncogenes are responsible for the proliferative, invasive, and aggressive nature of melanomas. High-resolution and high-throughput technology has led to the identification of distinct mutational signatures and their downstream alterations in several key pathways that contribute to melanomagenesis. This has enabled the development of individualized treatments by targeting specific molecular alterations that are vital for cancer cell survival, which has resulted in improved outcomes in several cancers, including melanomas. To date, BRAF and MEK inhibitors remain the only approved targeted therapy with a high level of evidence in BRAFV600E/K mutant melanomas. The lack of approved precision drugs in melanomas, relative to other cancers, despite harboring one of the highest rates of somatic mutations, advocates for further research to unveil effective therapeutics. In this review, we will discuss potential druggable mutations and the ongoing research of novel individualized treatment approaches targeting non-BRAF mutations in melanomas.

show abstract

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?

Cited by 7 publications

References 5 publications

Clinical outcomes and longitudinal circulating tumor DNA changes after treatment with nivolumab and olaparib in immunotherapy relapsed melanoma with detected homologous recombination deficiency

Clinical outcomes and longitudinal circulating tumor DNA changes after treatment with nivolumab and olaparib in immunotherapy relapsed melanoma with detected homologous recombination deficiency

Poly (ADP-Ribose) Polymerase inhibitors (PARPi) therapy response in an acral melanoma patient with EMSY gene amplification

Melanoma Targeted Therapies beyond BRAF-Mutant Melanoma: Potential Druggable Mutations and Novel Treatment Approaches

Contact Info

Product

Resources

About