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Better Understanding Genetic Mutations Influence in Cancer Care

Key Takeaways

  • Precision medicine in GU cancers is evolving with biomarkers like BRCA1/2 mutations influencing PARP inhibitor use and pembrolizumab's tumor-agnostic approval for microsatellite instability.
  • FGFR3 mutations and HER2 positivity in bladder cancer guide treatment with erdafitinib and fam-trastuzumab deruxtecan-nxki, respectively.
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Dr. Guru Sonpavde emphasized the importance of better understanding how genetic mutations influence the treatment of cancer care, particularly GU cancers.

Following the 2025 ASCO Genitourinary (GU) Cancers Symposium, Dr. Guru P. Sonpavde sat down for an interview with CURE® to discuss genetic testing and the importance of precision medicine in cancer care.

Sonpavde, the medical director of Genitourinary Oncology, an assistant director of the Clinical Research Unit, and the Christopher K. Glanz Chair for Bladder Cancer Research at the AdventHealth Cancer Institute, located in Orlando, Florida, emphasized the importance of better understanding how genetic mutations influence the treatment of cancer care, particularly in GU cancers, and went on to discuss the potential of precision care.

Glossary:

Minimal residual disease: the presence of a very small number of cancer cells that remain in the body after treatment, even when the patient is in remission.

Circulating tumor DNA (ctDNA): DNA that breaks away from cancer cells and enters the bloodstream

Transcript:

Precision medicine still has a ways to go. As we know, we use biomarkers in prostate and bladder cancer; obviously genomic or germline alterations in BRCA1 and BRCA2 has had a big impact on the use of PARP inhibitors. Of course, we also know that the tumor agnostic approval of Keytruda (pembrolizumab) based on microsatellite instability does have an impact across most cancers; in prostate cancer, that does apply.

In bladder cancer, at this time, the FGFR3 mutations/fusions that allows us to give Balversa [erdafitinib]. We are also looking for HER2. With HER2 [positivity], Enhertu [fam-trastuzumab deruxtecan-nxki] is approved as a pan-tumor approval label. Therefore, we look for those biomarkers in bladder cancer.

In renal cell carcinoma, it's a little unclear at the moment. The one biomarker that's looking interesting is the KIM-1, the circulating proteomic biomarker, which could be a reasonable biomarker for minimal residual disease. It seems to correlate with the recurrence of tumor post-operation. It also seems to correlate with long-term outcomes in the immune checkpoint inhibitor setting, as shown at the ASCO GU Symposium, [with the use of] Yervoy [ipilimumab] and Opdivo [nivolumab]. [Therefore], I think that biomarkers are emerging.

To add, I will say the minimal residual disease informs circulating tumor DNA [ctDNA] to select patients for adjuvant Opdivo. [On that note], immune checkpoint inhibition is being used in the community, however, prospective validation is still ongoing. For example, the IMvigor011 trial used ctDNA data to guide adjuvant therapy, as well as [guide] therapy at the time of transforming from ctDNA-negative to ctDNA-positive… Hopefully more data will come out from the IMvigor011 trial to further guide [this treatment].

There is a trial ongoing that allows patients to be de-intensified or intensified in terms of adjuvant therapy for high-risk muscle-invasive bladder cancer based on ctDNA-positive or -negative [status]. Overall, I think that all of these studies, when they mature, will bring precision medicine based on tumor alterations as well as MRD information to guide therapy.

Transcript has been edited for clarity and conciseness.

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