09 May VITRAKVI® (larotrectinib): Outcomes by Prior Treatment & Performance Status in TRK Fusion Cancer Patients

MedicalResearch.com Interview with:

Dr. Hong

David S Hong, M.D
MD Anderson
Department of Investigational Cancer Therapeutics
Division of Cancer Medicine
University of Texas

MedicalResearch.com: What is the background for this study?

Response: Larotrectinib is a first-in-class, CNS active, oral TRK inhibitor exclusively designed to treat tumors with an NTRK gene fusion and does not have secondary targets.

In previous presentations and published in The Lancet Oncology, larotrectinib demonstrated robust tumor-agnostic efficacy in an integrated dataset of 159 adult and pediatric patients with TRK fusion cancer across three clinical trials (Feb 2019 data cut-off date). In these studies, the objective response rate (ORR), according to investigator assessment, was 79% (95% confidence interval [CI], 72 – 85%), with a complete response rate of 16%.

In this analysis presented at AACR 2020, we sought to evaluate the outcomes in patients from the integrated data set based on different baseline characteristics, including prior lines of therapy and Eastern Cooperative Oncology Group (ECOG) performance status.

ECOG measures how the disease impacts a patient. ECOG describes a patient’s level of functioning with a numbering scale (0-5) so physicians can uniformly describe a patient’s ability to care for themselves, daily activity and physical activity (selfcare, walking, working, etc).

MedicalResearch.com: What are the main findings? 

Response: Results showed while response rates were highest in patients who were treatment-naïve or with an ECOG performance status of 0, patients treated with larotrectinib benefitted across varying degrees of pre-treatment or performance status:

• Stratified ORR based on prior lines of therapy included ORR of 91% for patients with 0 lines of prior therapy (n=35), ORR of 70% for patients with 1 line of prior therapy (n=48), ORR of 73% for patients with 2 lines of prior therapy (n=34), and ORR of 85% for patients with ≥3 lines of prior therapy (n=42).
• Stratified ORR based on ECOG performance status included ORR of 91% for patients with an ECOG status of 0 (n=76), ORR of 69% for patients with an ECOG status of 1 (n=61), ORR of 71% for patients with an ECOG status of 2 (n=19), and ORR of 33% for patients with an ECOG status of 3 (n=3).

The incidence of Grade 3/4 adverse events was similar across lines of therapy. 

MedicalResearch.com: What should readers take away from your report?

 Response: In general, we found that regardless of number of prior therapies – and to some extent regardless of ECOG – patients benefitted from larotrectinib.

These data overall demonstrate the importance of testing our patients to identify if they have NTRK gene fusions and may benefit from treatment with larotrectinib.

What recommendations do you have for future research as a result of this study?

As response rates were highest in patients who were treatment-naïve, it would be beneficial to see further research into the outcomes of treating with larotrectinib earlier in the treatment paradigm.

Additionally, as many patients have been on larotrectinib for several years now, the next steps would be to review the next generation therapies, such as one example: an investigational TRK inhibitor selitrectinib.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

 Response: As response rates were highest in patients who were treatment-naïve, it would be beneficial to see further research into the outcomes of treating with larotrectinib earlier in the treatment paradigm.

Additionally, as many patients have been on larotrectinib for several years now, the next steps would be to review the next generation therapies, such as one example: an investigational TRK inhibitor selitrectinib.

Any disclosures?

David S. Hong Disclosures (last 36 months)

• Research/Grant Funding: AbbVie, Adaptimmune, Aldi-Norte, Amgen, Astra-Zeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, GSK, Ignyta, Infinity, Kite, Kyowa, Lilly, LOXO, Merck, MedImmune, Mirati, miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfizer, Seattle Genetics, Takeda, Turning Point Therapeutics
• Travel, Accommodations, Expenses: Bayer, LOXO, miRNA, Genmab, AACR, ASCO, SITC
• Consulting or Advisory Role: Alpha Insights, Amgen, Axiom, Adaptimmune, Baxter, Bayer, eCancer, Genentech, GLG, Group H, Guidepoint, Infinity, Medscape, Numab, Oncology Education Project Association, Pfizer, Prime Oncology, Takeda, Trieza Therapeutics, WebMD
• Other ownership interests: Molecular Match (Advisor), OncoResponse (Founder), Presagia Inc (Advisor) 

Citation: AACR Virtual Meeting Abstract April 2020
Larotrectinib in TRK fusion cancer patients: Outcomes by prior therapy and performance status

 Alexander Drilon, Cornelis M. Van Tilburg, Anna F. Farago, Shivaani Kummar, Jordan Berlin, Catherine M. Albert, Ray McDermott, Ulrik N. Lassen, John A. Reeves, Nicoletta Brega, Barrett H. Childs, Theodore W. Laetsch, David S. Hong
https://www.abstractsonline.com/pp8/#!/9045/presentation/10700

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Last Updated on May 9, 2020 by Marie Benz MD FAAD