Add like
Add dislike
Add to saved papers

Navigating uncharted territory: a case report and literature review on the remarkable response to personalized crizotinib containing combinational therapy in a pazopanib refractory patient with novel alterations.

This paper presents a patient with a novel Ig-like-III domain fibroblast growth factor receptor (FGFR2) alteration (W290_P307>C) along with CDKN2A/B alterations and a cadherin 1 (CDH1) alteration. Initial responsiveness to pazopanib monotherapy was encouraging, yet progression occurred after 7.5 months. Following progression, the molecular tumor board recommended a combination therapy approach comprising pazopanib, crizotinib, and palbociclib to target all of the changed pathways at the same time. Pazopanib was chosen to specifically target the FGFR2 alteration, while crizotinib was selected due to its potential synthetic lethality with the CDH1 alteration. In addition, the CDK4/6 inhibitor palbociclib was administered to address the CDKN2A/B alterations. The patient exhibited a remarkable and sustained response to this innovative combination. This case not only underscores the potential of tyrosine kinase inhibitors, exemplified by pazopanib, as a viable alternative for patients without access to pan-FGFR inhibitors, but it also emphasizes their efficacy beyond commonly detected point mutations and rearrangements. Notably, the outstanding response to combination therapy, including crizotinib, in a patient with a CDH1 alteration, further substantiates the preclinical evidence of synthetic lethality between crizotinib and CDH1 alterations. To our knowledge, this represents the first clinical evidence demonstrating the efficacy of crizotinib in a patient with a CDH1 alteration. Through careful dosage adjustments and consideration of individualized genomic information, this case exemplifies the power of personalized medicine in achieving favorable treatment outcomes.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

Related Resources

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app