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Gene- and immune-targeted therapy combinations using dual-matched biomarkers for patient selection
Daisuke Nishizaki1, Razelle Kurzrock2,3, Jacob J Adashek4
1Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA. dnishizaki@health.ucsd.edu.
Abstract:
Combinations of gene-targeted therapy and immune checkpoint inhibitors (ICIs) have been conducted, though generally without biomarker-based patient selection for both therapy types. We evaluated outcomes of 17 patients with advanced cancers treated with both targeted agents and ICIs, matched to distinct genomic and immune biomarkers, from a cohort of 715 cases discussed at our Molecular Tumor Board. Despite 29% of patients having undergone ≥3 prior therapies, the disease control rate (includes SD ≥ 6 months or objective response) was 53%, with a median progression-free survival (PFS) of 6.1 months (95% CI, 2.9-not estimable) and median overall survival (OS) of 9.7 months (95% CI, 6.7-not estimable). Three patients (~18%) achieved prolonged PFS and OS (PFS: 23.4+, 33.0, 59.7 months; OS: 23.4+, 43.6, 62.1+ months) in B-cell lymphoma unclassifiable, ovarian, and gastroesophageal cancers. Median dosages were 100% for ICIs and 50% for gene-targeted agents, with Grade 3-4 serious adverse events occurring in 24%. We additionally conducted a database search to evaluate the prevalence of biomarker-based dual therapy trials, which revealed only 1.3% (4/314) of such clinical trials included biomarkers for both targeted therapies and ICIs. These findings highlight the potential of dual biomarker-matched combination therapy even after multiple therapy lines and support further investigation of dual-matched therapy.
Insights
Biomarker-matched combination therapy using targeted agents and immune checkpoint inhibitors (ICIs) shows promise in advanced cancers, even after multiple treatments. Further research into dual-matched therapies is warranted.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- Combinations of gene-targeted therapy and immune checkpoint inhibitors (ICIs) are used in advanced cancers.
- Patient selection for these dual therapies often lacks comprehensive biomarker matching for both treatment types.
Purpose of the Study:
- To evaluate the outcomes of advanced cancer patients treated with biomarker-matched targeted agents and ICIs.
- To assess the prevalence of clinical trials incorporating dual biomarker-based selection for targeted therapy and ICIs.
Main Methods:
- Retrospective analysis of 17 advanced cancer patients receiving dual therapy, matched to genomic and immune biomarkers.
- Database search to identify clinical trials using dual biomarker-based selection for targeted therapy and ICIs.
Main Results:
- Disease control rate of 53% in patients with advanced cancers, including those with ≥3 prior therapies.
- Median progression-free survival (PFS) of 6.1 months and overall survival (OS) of 9.7 months.
- Three patients (18%) achieved prolonged PFS and OS with specific cancer types; only 1.3% of trials utilized dual biomarker matching.
Conclusions:
- Dual biomarker-matched combination therapy demonstrates potential in advanced cancers, even in heavily pre-treated patients.
- Further investigation and development of dual-matched therapy strategies are supported by these findings.
- The limited number of current trials highlights a gap in biomarker-based dual therapy research.
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