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Clinical Trial
. 2021 Aug 1;39(22):2443-2451.
doi: 10.1200/JCO.20.02923. Epub 2021 Apr 12.

Pembrolizumab in Patients With Metastatic Breast Cancer With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Ajjai S Alva  1 , Pam K Mangat  2 , Elizabeth Garrett-Mayer  2 , Susan Halabi  3 , Damien Hansra  4 , Carmen J Calfa  5 , Maged F Khalil  6 , Eugene R Ahn  7 , Timothy L Cannon  8 , Pamela Crilley  9 , Julie G Fisher  10 , Derrick S Haslem  11 , Sagun Shrestha  12 , Kaitlyn R Antonelli  2 , Nicole L Butler  2 , Sasha L Warren  2 , Andrew L Rygiel  2 , Shamika Ranasinghe  2 , Suanna S Bruinooge  2 , Richard L Schilsky  2
Affiliations
Clinical Trial

Pembrolizumab in Patients With Metastatic Breast Cancer With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Ajjai S Alva et al. J Clin Oncol. .

Abstract

Purpose: The TAPUR Study is a phase II basket trial that aims to identify signals of antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Results in a cohort of patients with metastatic breast cancer (mBC) with high tumor mutational burden (HTMB) treated with pembrolizumab are reported.

Methods: Patients with advanced mBC received standard doses of either 2 mg/kg or 200 mg infusions of pembrolizumab every 3 weeks. Simon's two-stage design was used with a primary study end point of disease control (DC) defined as objective response or stable disease of at least 16 weeks duration. If two or more patients in stage I achieved DC, the cohort would enroll 18 additional patients in stage II. Secondary end points include progression-free survival (PFS), overall survival, and safety.

Results: Twenty-eight patients were enrolled from October 2016 to July 2018. All patients' tumors had HTMB ranging from 9 to 37 mutations/megabase. DC and objective response were noted in 37% (95% CI, 21 to 50) and 21% of patients (95% CI, 8 to 41), respectively. Median PFS was 10.6 weeks (95% CI, 7.7 to 21.1); median overall survival was 30.6 weeks (95% CI, 18.3 to 103.3). No relationship was observed between PFS and tumor mutational burden. Five patients experienced ≥ 1 serious adverse event or grade 3 adverse event at least possibly related to pembrolizumab consistent with the product label.

Conclusion: Pembrolizumab monotherapy has antitumor activity in heavily pretreated patients with mBC characterized by HTMB. Our findings support the recent US Food and Drug Administration approval of pembrolizumab for treatment of patients with unresectable or metastatic solid tumors with HTMB without alternative treatment options.

Trial registration: ClinicalTrials.gov NCT02693535.

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Conflict of interest statement

Ajjai S. AlvaConsulting or Advisory Role: AstraZeneca, Merck, Pfizer, Bristol Myers SquibbResearch Funding: Genentech, Bristol-Myers Squibb, Merck Sharp & Dohme, Prometheus, Mirati Therapeutics, AstraZeneca, Roche, Bayer, Progenics, Astellas Pharma, Arcus Biosciences, Harpoon Therapeutics, Progenics, Celgene, JanssenTravel, Accommodations, Expenses: Merck, Bristol Myers Squibb Elizabeth Garrett-MayerConsulting or Advisory Role: Deciphera, TYME Susan HalabiEmployment: ASCOConsulting or Advisory Role: Eisai, Ferring Pharmaceuticals Damien HansraEmployment: Cancer Treament Centers of America, Hansra Health Corporation Eugene R. AhnEmployment: Cancer Treament Centers of AmericaLeadership: Cancer Treament Centers of America Timothy L. CannonConsulting or Advisory Role: Loxo, NavicanOther Relationship: Navican/Intermountain Healthcare Pamela CrilleyEmployment: Cancer Treament Centers of AmericaLeadership: Cancer Treament Centers of AmericaTravel, Accommodations, Expenses: Cancer Treament Centers of America Richard L. SchilskyResearch Funding: AstraZeneca, Bayer, Bristol-Myers Squibb, Genentech/Roche, Lilly, Merck, Pfizer, Boehringer IngelheimOpen Payments Link: https://openpaymentsdata.cms.gov/physician/1138818/summaryNo other potential conflicts of interest were reported.

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