Somatic Genomic Testing in Patients With Metastatic or Advanced Cancer: ASCO Provisional Clinical Opinion

Chakravarty, Debyani; Johnson, Amber; Sklar, Jeffrey; Lindeman, Neal I.; Moore, Kathleen; Ganesan, Shridar; Lovly, Christine M.; Perlmutter, Jane; Gray, Stacy W.; Hwang, Jimmy J.; Lieu, Christopher H.; Varga, Andrea; Azad, Nilofer S.; Borad, Mitesh J.; Tafe, Laura J.; Messersmith, Hans; Robson, Mark E.; Meric‐Bernstam, Funda

doi:10.1200/jco.21.02767

Cited by 123 publications

(103 citation statements)

References 214 publications

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“…Patient-Clinician Communication 49 (http://ascopubs.org/doi/10.1200/JCO.2017.75.2311)Integration of Palliative Care into Standard Oncology Care 53 (http://ascopubs.org/doi/10.1200/JCO.2016.70.1474)Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer 50 (http://ascopubs.org/doi/10.1200/JCO.22.00069)Somatic Genomic Testing in Patients With Metastatic or Advanced Cancer 54 (https://ascopubs.org/doi/10.1200/JCO.21.02767)…”

Section: Additional Resourcesmentioning

confidence: 99%

Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update

Henry

Somerfield

Dayao

et al. 2022

JCO

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PURPOSE To update the ASCO biomarkers to guide systemic therapy for metastatic breast cancer (MBC) guideline. METHODS An Expert Panel conducted a systematic review to identify randomized clinical trials and prospective-retrospective studies from January 2015 to January 2022. RESULTS The search identified 19 studies informing the evidence base. RECOMMENDATIONS Candidates for a regimen with a phosphatidylinositol 3-kinase inhibitor and hormonal therapy should undergo testing for PIK3CA mutations using next-generation sequencing of tumor tissue or circulating tumor DNA (ctDNA) in plasma to determine eligibility for alpelisib plus fulvestrant. If no mutation is found in ctDNA, testing in tumor tissue, if available, should be used. Patients who are candidates for poly (ADP-ribose) polymerase (PARP) inhibitor therapy should undergo testing for germline BRCA1 and BRCA2 pathogenic or likely pathogenic mutations to determine eligibility for a PARP inhibitor. There is insufficient evidence for or against testing for a germline PALB2 pathogenic variant to determine eligibility for PARP inhibitor therapy in the metastatic setting. Candidates for immune checkpoint inhibitor therapy should undergo testing for expression of programmed cell death ligand-1 in the tumor and immune cells to determine eligibility for treatment with pembrolizumab plus chemotherapy. Candidates for an immune checkpoint inhibitor should also undergo testing for deficient mismatch repair/microsatellite instability-high to determine eligibility for dostarlimab-gxly or pembrolizumab, as well as testing for tumor mutational burden. Clinicians may test for NTRK fusions to determine eligibility for TRK inhibitors. There are insufficient data to recommend routine testing of tumors for ESR1 mutations, for homologous recombination deficiency, or for TROP2 expression to guide MBC therapy selection. There are insufficient data to recommend routine use of ctDNA or circulating tumor cells to monitor response to therapy among patients with MBC. Additional information can be found at www.asco.org/breast-cancer-guidelines .

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Section: Additional Resourcesmentioning

confidence: 99%

Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update

Henry

Somerfield

Dayao

et al. 2022

JCO

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“…Traditionally, BRCA testing has been conducted in germline DNA triggered by a familial aggregation of cancer. Recent studies have demonstrated that a significant proportion of mutation carriers are undiagnosed due to the lack of a significant family history of cancer [ 18 , 42 , 98 ], leading to changes in the recommendations for genetic testing. As an example, testing is now recommended for all metastatic prostate cancer patients, regardless of their personal or family history of cancer [ 99 ].…”

Section: The Challenge Of Testing: Searching For Hrd Scarmentioning

confidence: 99%

“…ESMO and NCCN guidelines [ 98 , 101 , 102 ] recommend pre-test counseling to determinate the most appropriate test for each patient and specific post-test counseling when results are available. Table 3 summarizes the current recommendations for testing based on international clinical guidelines.…”

Section: The Challenge Of Testing: Searching For Hrd Scarmentioning

confidence: 99%

The Homologous Recombination Deficiency Scar in Advanced Cancer: Agnostic Targeting of Damaged DNA Repair

Pacheco-Barcía

Muñoz

Castro

et al. 2022

Cancers

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BRCA1 and BRCA2 are the most recognized tumor-suppressor genes involved in double-strand DNA break repair through the homologous recombination (HR) system. Widely known for its role in hereditary cancer, HR deficiency (HRD) has turned out to be critical beyond breast and ovarian cancer: for prostate and pancreatic cancer also. The relevance for the identification of these patients exceeds diagnostic purposes, since results published from clinical trials with poly-ADP ribose polymerase (PARP) inhibitors (PARPi) have shown how this type of targeted therapy can modify the long-term evolution of patients with HRD. Somatic aberrations in other HRD pathway genes, but also indirect genomic instability as a sign of this DNA repair impairment (known as HRD scar), have been reported to be relevant events that lead to more frequently than expected HR loss of function in several tumor types, and should therefore be included in the current diagnostic and therapeutic algorithm. However, the optimal strategy to identify HRD and potential PARPi responders in cancer remains undefined. In this review, we summarize the role and prevalence of HRD across tumor types and the current treatment landscape to guide the agnostic targeting of damaged DNA repair. We also discuss the challenge of testing patients and provide a special insight for new strategies to select patients who benefit from PARPi due to HRD scarring.

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“…Another relevant aspect to consider is the timing when to perform NGS in cancer patients. Although the presence of tumor-agnostic markers ( NTRK fusions, TMB and MSI) provides the premise for the use of sequencing in all tumors [ 59 ], ESMO guidelines recommend NGS just for patients with non-squamous NSCLC, ovarian carcinoma, prostate carcinoma and cholangiocarcinoma, so that, other than in these indications, the use of NGS should be considered on a case-by-case basis [ 60 ]. However, data from our analysis also highlight that about 20% of patients with a therapeutic suggestion from our MTB did not receive any systemic treatment following the MTB because of death or poor performance status not allowing further therapy.…”

Section: Discussionmentioning

confidence: 99%

Combined Focused Next-Generation Sequencing Assays to Guide Precision Oncology in Solid Tumors: A Retrospective Analysis from an Institutional Molecular Tumor Board

Tarawneh

Rodepeter

Teply-Szymanski

et al. 2022

Cancers

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Background: Increasing knowledge of cancer biology and an expanding spectrum of molecularly targeted therapies provide the basis for precision oncology. Despite extensive gene diagnostics, previous reports indicate that less than 10% of patients benefit from this concept. Methods: We retrospectively analyzed all patients referred to our center’s Molecular Tumor Board (MTB) from 2018 to 2021. Molecular testing by next-generation sequencing (NGS) included a 67-gene panel for the detection of short-sequence variants and copy-number alterations, a 53- or 137-gene fusion panel and an ultra-low-coverage whole-genome sequencing for the detection of additional copy-number alterations outside the panel’s target regions. Immunohistochemistry for microsatellite instability and PD-L1 expression complemented NGS. Results: A total of 109 patients were referred to the MTB. In all, 78 patients received therapeutic proposals (70 based on NGS) and 33 were treated accordingly. Evaluable patients treated with MTB-recommended therapy (n = 30) had significantly longer progression-free survival than patients treated with other therapies (n = 17) (4.3 vs. 1.9 months, p = 0.0094). Seven patients treated with off-label regimens experienced major clinical benefits. Conclusion: The combined focused sequencing assays detected targetable alterations in the majority of patients. Patient benefits appeared to lie in the same range as with large-scale sequencing approaches.

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Somatic Genomic Testing in Patients With Metastatic or Advanced Cancer: ASCO Provisional Clinical Opinion

Cited by 123 publications

References 214 publications

Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update

Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update

The Homologous Recombination Deficiency Scar in Advanced Cancer: Agnostic Targeting of Damaged DNA Repair

Combined Focused Next-Generation Sequencing Assays to Guide Precision Oncology in Solid Tumors: A Retrospective Analysis from an Institutional Molecular Tumor Board

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