Clinical outcomes of tumor-agnostic targeting of BRAF, tumor mutation burden-high, and RET

Q: What tumor-agnostic targets are evaluated in the study?

The study evaluates BRAF V600E mutations, high tumor mutational burden (TMB-H), and RET fusions as three molecular alteration classes treated with genomically matched therapies.

Q: How many patients were assessed, and how were they selected?

A retrospective cohort of 10,893 patients who underwent next-generation sequencing (NGS) from February 2020 to May 2022 was analyzed for the prevalence of the three agnostic targets.

Q: What outcomes were compared between GMT and non-GMT?

The objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) were compared between GMT and non-GMT within each alteration cohort.

Sep 24, 2026

Uploaded by Stanley

Clinical outcomes are reported for three tumor-agnostic genomic targets—BRAF p.V600E (BRAF V600E) mutations, high tumor mutational burden (TMB-H), and RET fusions—using genomically matched therapies (GMTs). The KISMET project was established to provide real-world evidence on GMT implementation and patient outcomes. In a retrospective NGS cohort of 10,893 advanced cancer patients assessed from Feb 2020 to May 2022, objective response rate and survival endpoints were compared between GMT and non-GMT groups within each alteration class.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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Background

Patients and methods

Results

Conclusions

Introduction

ORIGINAL ARTICLE Clinical outcomes of tumor-agnostic targeting of BRAF, tumor mutation burden-high, and RET A. Ronaghy1, E. Crimini1, 2, V. R. Holla1, K. R. Mills Shaw3, A. M. Doeﬂer1, E. Campbell1, R. K. Yang4, J. B. Iorgulescu5, K. P. Patel5, D. D. McPherson6, J. Ning7, F. Meric-Bernstam1 􀀁 & D. D. Karp1 1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA; 2Department of Oncology and HematoOncology, University of Milan, Milan, Italy; 3Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston; 4Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston; 5Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston; 6Division of Cardiology, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston; 7Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA Available online xxx Background: We report the BRAF p.V600E (BRAF V600E) mutations, high tumor mutational burden (TMB-H), and RET fusions frequency/outcomes with genomically matched therapies (GMTs) . To raise awareness about GMTs providing data from a real-world scenario, the KISMET project was created. In this article we report the characteristics and the outcomes of patients with advanced cancer harboring three different classes of molecular alterations: BRAFV600E mutations, TMB-H, and RET fusions. Patients and methods: We retrospectively assessed the prevalence of the three aforementioned agnostic targets among 10893 patients who underwent next-generation sequencing (NGS) from February 2020 to May 2022 . We evaluated the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) for GMT versus non-GMT in the three cohorts of patients with each speciﬁc alteration. Results: BRAF V600E occurred in 6 .5%(662/10158) of patients, TMB-H in 11 . 2%(265/2369), and RET fusions in 0 .6%(42/7105) . GMT was given to 115 (72 .3%) out of the 159 patients who started a new line of treatment after NGS testing: 65 of 85 with BRAF V600E mutations, 42 of 65 for TMB-H, and 8 of 9 for RET fusions. The ORR of GMT versus non-GMT was 55 .6% versus 12 .8% for all patients (P < 0.0001), 51% versus 17 .6% for the BRAF V600E (P ¼ 0.016), 57 .6% versus 9.5% for the TMB-H (P ¼ 0.004), and 75% versus 0% for RET fusions (P ¼ 0.30) . The mPFS for GMT versus non-GMT was 9.6 versus 3 .7 months (P ¼ 0.001), 9 . 2 versus 4 . 2 months (P ¼ 0.08) for BRAF V600E, and 7 .9 versus 3 .7 months (P ¼ 0.04) for TMB-H, respectively. For the eight patients with RET fusions who received RET inhibitors, the mPFS was 15 .0 months. Conclusions: BRAF V600E, TMB-H, and RET fusion were found in a wide variety of advanced cancers. Improved oncological outcomes with tumor type-agnostic GMT support the value of integrating comprehensive NGS testing and GMT administration for the aforementioned targets. Key words: precision oncology, targeted therapies, real-world, BRAF, tumor mutational burden, RET INTRODUCTION The goal of precision oncology is to utilize therapies tailored to the individual molecular proﬁle of each cancer patient.1-6 Different techniques based on the biomarker, the sample, and cost considerations can assess the biomarkers *Correspondence to: Prof. Funda Meric-Bernstam, Chair, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 455, Faculty Center, 8th Floor, Houston, TX 77030, USA. Tel: þ1-713-794- 1226; Fax: þ1-713-563-0566 E-mail: [fmeric@mdanderson.org](fmeric@mdanderson.org) (F. Meric-Bernstam). 2059-7029/© 2025 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article

FAQs

What tumor-agnostic targets are evaluated in the study?

The study evaluates BRAF V600E mutations, high tumor mutational burden (TMB-H), and RET fusions as three molecular alteration classes treated with genomically matched therapies.

How many patients were assessed, and how were they selected?

A retrospective cohort of 10,893 patients who underwent next-generation sequencing (NGS) from February 2020 to May 2022 was analyzed for the prevalence of the three agnostic targets.

What outcomes were compared between GMT and non-GMT?

The objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) were compared between GMT and non-GMT within each alteration cohort.

Sep 24, 2026

Uploaded by Stanley