Assessment of Clinical Benefit of Integrative Genomic Profiling in Advanced Solid Tumors

Cobain, Erin F.; Wu, Yi-Mi; Vats, Pankaj; Chugh, Rashmi; Worden, Francis P.; Smith, David C.; Schuetze, Scott M.; Zalupski, Mark M.; Sahai, Vaibhav; Alva, Ajjai; Schott, Anne F.; Caram, Megan Veresh; Hayes, Daniel F.; Stoffel, Elena M.; Jacobs, Michelle F.; Kumar-Sinha, Chandan; Cao, Xuhong; Wang, Rui; Lucas, David R.; Yu, Na; Rabban, Erica; Bell, Janice F.; Camelo-Piragua, Sandra; Udager, Aaron M.; Cieślik, Marcin; Lonigro, Robert J.; Kunju, Lakshmi P.; Robinson, Dan R.; Talpaz, Moshe; Chinnaiyan, Arul M.

doi:10.1001/jamaoncol.2020.7987

Cited by 103 publications

(143 citation statements)

References 34 publications

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“…Indeed, extensive testing is required to select only a few treatable patients. Nevertheless, we expect that screening gene alterations or amplifications by next-generation sequencing techniques may become routine in the near future and will allow us to detect several targets simultaneously [15,16]. Indeed, only 31% of patients with MET-amplified tumor were enrolled in our study.…”

Section: Discussionmentioning

confidence: 99%

The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSé-Crizotinib Program

et al. 2021

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Background The AcSé-crizotinib program provides extensive screening of crizotinib-targeted genomic alteration in several malignancies. We here report the results in patients with esogastric MET-amplified adenocarcinomas. Objective The objective of the study was to evaluate the efficacy and tolerability of crizotinib in patients with pretreated esogastric MET-amplified adenocarcinoma who have no alternative treatment options. Patients and Methods MET expression was evaluated by fluorescence in situ hybridization in tumor samples with immunohistochemistry scores ≥ 2+. Patients with chemo-refractory tumors showing ≥ 6 MET copies were eligible for crizotinib 250 mg twice daily. The primary efficacy outcome was the objective response rate after two cycles of crizotinib. Results MET was prospectively analyzed in 570 esogastric adenocarcinomas. Amplifications were found in 35/570 adenocarcinomas (29/523 gastric and 6/47 esophageal). Nine patients were treated with crizotinib. The objective response rate after two cycles was 33.3% (95% CI 7.5-70), the best overall response rate was 55.6% (95% CI 21.2-86.3), with median progression-free survival of 3.2 months (95% CI 1.0-5.4), and overall survival of 8.1 months (95% CI 1.7-24.6). Safety was consistent with that previously reported for crizotinib. Conclusions Large-scale screening for MET-amplified esogastric adenocarcinomas is feasible. MET amplification was observed in 5.5% of gastric and 12.8% of esophageal adenocarcinomas. Crizotinib shows encouraging results in selected patients. Thus, c-MET inhibition for MET-amplified tumors deserves further evaluation. Trial Registration Number NCT02034981.

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Section: Discussionmentioning

confidence: 99%

The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSé-Crizotinib Program

et al. 2021

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“…Several clinical trials have indicated that using multi-gene testing to personalize cancer therapies can have a positive impact on tumor response rates and patient progression-free survival, as well as on finding new molecularly-targeted treatment indications [140][141][142]. Multi-gene testing is considered the most appropriate option for patients with advanced or metastatic cancers with limited standard-of-care options in order to assess several actionable genomic alterations at the same time [143].…”

Section: Clinical Utility Of Multi-gene Testing For Metastatic Triple-negative Breast Cancermentioning

confidence: 99%

Multi-Gene Testing Overview with a Clinical Perspective in Metastatic Triple-Negative Breast Cancer

Dameri

Ferrando

Cirmena

et al. 2021

IJMS

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Next-generation sequencing (NGS) is the technology of choice for the routine screening of tumor samples in clinical practice. In this setting, the targeted sequencing of a restricted number of clinically relevant genes represents the most practical option when looking for genetic variants associated with cancer, as well as for the choice of targeted treatments. In this review, we analyze available NGS platforms and clinical applications of multi-gene testing in breast cancer, with a focus on metastatic triple-negative breast cancer (mTNBC). We make an overview of the clinical utility of multi-gene testing in mTNBC, and then, as immunotherapy is emerging as a possible targeted therapy for mTNBC, we also briefly report on the results of the latest clinical trials involving immune checkpoint inhibitors (ICIs) and TNBC, where NGS could play a role for the potential predictive utility of homologous recombination repair deficiency (HRD) and tumor mutational burden (TMB).

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“…In this regard, the Molecular Tumor Board (MTB) plays a fundamental role in this phase of development of precision medicine both to ensure the prescriptive appropriateness of the CGP tests and to warrant the correct interpretation of the test results and their clinical application. In fact, many clinicians have limited confidence in the interpretation of multigene next-generation sequencing (NGS) tests [9,10].…”

Section: Evidencementioning

confidence: 99%

Transarterial Chemoembolization Alone or Followed by Bevacizumab for Treatment of Colorectal Liver Metastases

et al. 2021

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Aims: Bevacizumab (B) in association with systemic chemotherapy is commonly used for the treatment of colorectal cancer liver metastases. The aim of this study was to monitor tumor response, overall survival (OS) and progression-free survival (PFS) of patients with colorectal cancer liver metastases treated with transarterial chemoembolization (TACE) + B compared with TACE alone and to correlate the results with KRAS mutational status. Patients & methods: This was an observational multicentric case–control study (NCT03732235) on the efficacy and safety of B administered after TACE. Results: The disease control rate was significantly higher for the TACE + B than the TACE alone group (p < 0.001). KRAS wild-type patients had a significantly better disease control rate than those with KRAS mutations in the TACE + B group. Median OS and PFS were similar for the TACE + B and TACE groups, whereas median time to progression was significantly higher for the TACE + B group (p < 0.01). Conclusion: The combination of TACE with B may improve tumor response and delay disease progression.

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Assessment of Clinical Benefit of Integrative Genomic Profiling in Advanced Solid Tumors

Cited by 103 publications

References 34 publications

The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSé-Crizotinib Program

The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSé-Crizotinib Program

Multi-Gene Testing Overview with a Clinical Perspective in Metastatic Triple-Negative Breast Cancer

Transarterial Chemoembolization Alone or Followed by Bevacizumab for Treatment of Colorectal Liver Metastases

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