Our interview with RETexpert Dr. Tejas Patil

Our interview with RETexpert Dr. Tejas Patil

RETpositive is excited to introduce you to Tejas Patil, Assistant Professor, Medicine-Medical Oncology, University of Colorado, School of Medicine. Dr. Patil is a 2022 Lungevity/Hamoui Foundation awardee for his research on MET and EGFR as biomarkers for amivantamab in overcoming RET TKI resistance. We are proud to list Dr. Patil as a RETexpert for experience and expertise in RET-positive oncology.

We will learn more about Dr. Patil's background and career, as well as the important work he is doing to improve the lives of patients with cancer. Here is a Q&A he recently did with RETpositive.

RETpositive:  Why did you get involved in oncology? What makes you hopeful about lung cancer treatment?

Dr. Patil:  In addition to music, I focused on neuroscience during my undergraduate years and thought that I would be involved with brain research in medical school. During my first summer of medical school, I participated in the Childrens Hospital Summer Oncology Fellowship in Los Angeles, CA. I was paired with Dr. Mark Krieger, a neurosurgeon who specialized in pediatric brain and spine tumors. I had minimal to no experience with oncology going into this summer internship. However, I quickly fell in love with the field.

It is one of the few disciplines that merges emotional sensitivity with cutting edge science. I started focusing on thoracic malignancies with Dr. Ross Camidge and Dr. Bob Doebele once I started my residency at the University of Colorado and have been working in this space ever since. The thing that makes me hopeful about lung cancer treatment is the pace of progress. Outside of better anti-cancer treatments, there are continual new discoveries into novel biomarkers and a more refined understanding of cancer biology at a molecular level.

RETpositive: Are there any plans in the works for immunotherapy that will target RET?

Dr. Patil: The lack of benefit with immune checkpoint inhibitors (such as pembrolizumab) among RET-positive patients has been well described. However, immunotherapy is a broader category of treatment. This category includes therapies that targets different aspects of the immune system. Therapies that are currently being explored include T cell engagers, oncolytic vaccines, and tumor infiltrating lymphocytes (TILs). Right now, we don't have enough data to say which of these categories could help patients with RET fusions specifically, but this is being studied.

RETpositive: How do we help our care team and oncologists learn more and understand RET-positive?

Dr. Patil: With patients who have lung cancer with rare mutations (such as RET fusions), it is important that the care team, oncologist and patient have trust and humility. These are rare tumors and not every oncologist will have experience with them or even with the RET specific therapies such as selpercatinib or pralsetinib. The key point here is to recognize that these RET fusions are very treatable. When in doubt, it is okay to get a second opinion from a center that does see a lot of RET positive patients. The idea here is to form collaborative partnerships between a RET specialist, the patient's care team, and the patient.

RETpositive:  Many of RET-positive patients would like to know about the long term effects of taking RET inhibitors. Please comment.

Dr. Patil: I think the long-term effect of RET inhibitors (or most targeted therapies) continues to evolve. Many of the side effects from RET-specific therapies include hypertension, elevated liver enzyme tests and myalgias (muscle aches). An interesting side effect that has emerged with both selpercatinib and pralsetinib is the development of chylous effusions and ascites.

This is a rare side effect where the patient can develop a milky fluid that forms in the lungs and abdomen. It can be mistaken for cancer progression and so when in doubt, it is always best to sample pleural or peritoneal fluid and specifically send assess the triglyceride level.

They will often be markedly elevated. Where we need more research is what is the long-term quality of life issues for patients who have been on these therapies for years.

RETpositive: What 2nd line of defense drugs are being developed?

Dr. Patil: One of the challenging aspects of taking care of patients with RET positive patients is that cancers do evolve resistance to RET-targeted therapies. There are several trials looking at novel treatments that overcome common resistance mutations.

In general, there are three categories of resistance:

  1. On-target resistance where a specific mutation develops adjacent to the RET mutation that prevents the targeted therapy from working. (2)
  2. Off-target resistance where the cancer cell starts using some other signaling pathway to survive, and
  3. Histological transformation, where the lung cancer literally changes its sub-type (that is, a non-small cell lung cancer transforms to a small cell lung cancer).

RETpositive: Do you have any updates on research and clinical trials you can share?

Dr. Patil: Thankfully many clinical trials for RET positive patients who are not responding to first line RET treatments (selpercatinib or pralsetinib) are ongoing. TAS0953/HM06 is a new RET drug in clinical development that appears to have activity against the RET G810R/S/C mutations and also appears to have good brain penetration. Another drug that is similar is EP0031-101, which is also in clinical trial development.

There are also novel trials in development that are trying to target off-target resistance mechanisms, including a clinical trial of mine that will open at the University of Colorado, University of Michigan, and Mass General using amivantamab with either selpercatinib (or pralsetinib) in RET positive patients progressing on targeted therapies.

RETpositive: Can a RET fusion be passed onto children (hereditary)? If so, when would be the ideal time to have them tested?

Dr. Patil: As far as we are aware, RET fusions are somatic, but not germline (hereditary) mutations and so there does not appear to be an increased risk of transmission to children.

RETpositive: Is there a tipping point when the drugs kick in?

Dr. Patil: Targeted therapies (using drugs like selpercatinib or pralsetinib) typically work within 5 - 10 days. Most patients notice rapid improvement in symptoms.

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