Dr. Meghna Trivedi, an oncologist at NewYork-Presbyterian and Columbia, discusses new research she is leading to assess risk, and eventually prevent, chemotherapy induced peripheral neuropathy, a common side effect of cancer treatment that can have life-altering consequences for patients.
On this episode of Advances in Care, host Erin Welsh hears from Dr. Meghna Trivedi, an oncologist at NewYork-Presbyterian and Columbia, who is spearheading new research to assess cancer patients’ risk of developing chemotherapy induced peripheral neuropathy–an all too common side effect of cancer treatment.
Dr. Trivedi describes a study that she and her team undertook to identify and assess patient risk for developing a specific type of chemotherapy-induced neuropathy called TIPN, which is caused by taxanes, a commonly used chemotherapy drug. Based on this SWOG trial, known as S1714, physicians are better able to monitor at-risk patients for these side effects and adjust their treatment regimens accordingly.
Then, Dr. Trivedi explains how her team–also led by Dr. Daniel Hertz, PharmD, PhD at the University of Michigan–was recently awarded a prestigious R37 grant to identify a biomarker for TIPN. This study, which she co-leads with Dr. Daniel Hertz, PharmD, PhD at the University of Michigan, will help doctors understand the mechanisms for why TIPN develops in the first place, and will be a critical step forward in creating targeted therapies to treat this disease before it starts.
Finally, Dr. Trivedi dives into the clinical trials her team is currently conducting to identify new therapeutic approaches to address and prevent the effects of neuropathy, such as cryotherapy.
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Dr. Meghna Trivedi, is a medical oncologist at NewYork-Presbyterian and co-leads the Hereditary Breast and Ovarian Cancer Program at Columbia’s Herbert Irving Comprehensive Cancer Center, a comprehensive, multi-disciplinary initiative aimed at screening, preventing, diagnosing, and treating hereditary breast and ovarian cancer. This innovative program brings together the resources of a world-renowned academic institution, including cutting-edge genomic testing, clinical trials, and experts in hereditary cancers across different specialties. Dr. Trivedi’s research and care expertise also includes cancer genetics and genomics, precision medicine, and chemotherapy induced peripheral neuropathy. She is the principal investigator on several clinical trials, and has authored numerous publications in leading peer-reviewed journals.
To learn more about the SWOG trial visit swog.org/clinical-trials/s1714
For more information visit nyp.org/Advances
Dr. Meghna Trivedi: Chemotherapy induced peripheral neuropathy is a toxicity that can be quite debilitating.
Erin: This is Dr. Meghna Trivedi, a breast oncologist at NewYork-Presbyterian and Columbia.
Dr. Meghna Trivedi: Sometimes it can be painful neuropathy, so almost like an electrical kind of shock feeling. It can also manifest as motor weakness, so patients can lose their balance, making it difficult for them to walk.
Erin: Chemotherapy induced peripheral neuropathy is often caused by a common class of chemotherapy drugs called taxanes. When patients develop these neuropathies, they face an additional challenge on top of an already difficult diagnosis: they need to treat their cancer, and deal with disruptive, potentially long-term, side effects.
Dr. Meghna Trivedi: It can significantly impact people's quality of life through the development of numbness and tingling in the fingers and toes. In people that use their hands for a living, musicians and artists, this can really be a life changing toxicity that can impact them.
Erin: Due to the efficacy of taxanes, about 50% of breast cancer patients are treated with these medications. And of those patients, about 60-70% will go on to develop some level of neuropathy. Dr. Trivedi is driven to find ways to help this large group of patients avoid these life-altering side effects.
Although many people can be affected, it’s proved difficult to predict exactly which patients will go on to develop neuropathy. That’s why Dr. Trivedi is spearheading ground-breaking research as the Primary Investigator for a number of studies to identify risk factors and prevention methods for TIPN– taxane induced peripheral neuropathy.
Dr. Meghna Trivedi: We are always looking to see how we can make things better, and I think that's one of the most exciting parts of this type of research and oncology.
Erin: Dr. Trivedi’s studies are tackling a challenge that’s been difficult to address: standardizing the definition of what constitutes TIPN. Thus charting a new course for individualized cancer care. So that patients who are already meeting the challenge of cancer treatment, don’t have to suffer through additional emotional and physical pain.
Dr. Meghna Trivedi: We're really trying to individualize this approach to not only improve the outcomes for our patient, but also to try and minimize the toxicity to make things more tolerable and manageable.
Erin: I'm Erin Welsh and this is Advances in Care, a podcast about groundbreaking developments in modern medicine.
Today I’m speaking with Dr. Meghna Trivedi, Medical Oncologist at NewYork Presbyterian and co-lead of the Hereditary Breast and Ovarian Cancer Program at Columbia. We dig into the foundational research she is leading to establish the prevalence of TIPN, and create new standards for risk assessment and prevention. Her work promises to revolutionize treatment options and holistically improve outcomes and long-term quality of life for cancer patients.
Erin: Dr. Trivedi, it's lovely to meet you. Thank you so much for joining me today.
Dr. Meghna Trivedi: Thank you so much for the invitation to speak with you.
Erin: So let’s dive right in and talk about your research into some of the adverse effects associated with cancer treatments, specifically chemotherapy induced peripheral neuropathy, or CIPN. What is CIPN? And what makes it so challenging to predict?
Dr. Meghna Trivedi: So chemotherapy induced peripheral neuropathy is a toxicity that comes from a variety of different anti-cancer or anti-neoplastic agents. And most notably from breast cancer and in other types of cancer the group of drugs called taxanes. Taxanes are very commonly used in a lot of different types of cancers and are very effective.
Chemotherapy induced peripheral neuropathy can manifest in a variety of different ways. It can be sensory symptoms, motor symptoms, autonomic symptoms. They can also happen at various points throughout the treatment course. So some people develop it while they're on treatment and it can change over time.
Some patients develop it after their treatment is completed. So the timeline can also be very different depending on the individual. And so defining it, it can be tricky. And I think that's one of the challenges of a lot of the studies that have been done in the past is that there have been various different ways to define these symptoms. And so trying to establish what is the prevalence, how often are we seeing this? You know, you can see a variety of ranges, but the data shows that as many as 70% of patients that are receiving taxanes can develop some degree of taxane induced peripheral neuropathy.
Erin: That is a very high proportion. And in terms of that range you mentioned, I know that even the definition of what symptoms constitute TIPN has been somewhat murky in past studies. And I imagine that establishing and standardizing prevalence must be a crucial part of this research, so that clinicians can really understand and treat the true scope of this issue.
So I'm curious– and I know you’re the Primary Investigator on several studies related to TIPN– but specifically, how have you approached standardizing symptoms and creating a risk assessment model for TIPN?
Dr. Meghna Trivedi: So I lead a large observational cohort study focused on taxane induced peripheral neuropathy. And the primary objective of this study was to develop and validate a TIPN risk prediction model that could be readily applied in the clinic setting. And in this study we included patients with non-metastatic breast, lung, and ovarian cancer who were undergoing treatment with a taxane based chemotherapy regimen.
So this trial enrolled from 2019 until 2021. We enrolled over 1300 participants to this study and over the course of three years, they were serially evaluated for neuropathy using a wide range of different measurements.
So we used patient reported outcome measures, clinician assessed measures, as well as neurosensory and functional testing. And in addition participants could also submit biospecimens or blood samples for future biomarker research. And so in order to develop this risk prediction model, we had to define that TIPN has developed. And we used the patient reported outcome measure, the E-O-R-T-C-C-I-P-N 20 which is 20 questions that the patient completes. And we defined the primary endpoint using this patient reported outcome measure.
So a novel way to try and identify the risk factors of this very common toxicity among a large group of patients that had a consistent way of reporting TIPN or, or neuropathy symptoms.
Erin: So with this study you’re kind of casting a wide net and saying, okay, what are some of the factors that we see as being predictive for developing TIPN at some point during treatment or during these three years of follow up? What risk factors were you looking at at the outset, and then what ended up being included in the final model?
Dr. Meghna Trivedi: Through the study we collected a large amount of data on demographics and, you know, baseline health conditions, just details about the treatment regimen as well. Which kind of taxane did they receive? We limited it to Paclitaxel and docetaxel in this study. How frequently were they getting the chemotherapy? What was the planned duration of the chemotherapy?
And so we used all of these treatment, patient and disease-based factors and evaluated through this model development whether they could predict the development of taxane induced peripheral neuropathy.
And we presented this work at the 2024 ASCO annual meeting as an oral abstract presentation. And we were able to show that by 24 weeks from registration that the rate of taxane induced peripheral neuropathy was about 62%, which is a very, you know, high number.
Erin: Yeah, that’s a very high prevalence. So with that prevalence established, were you able to identify any significant risk factors?
Dr. Meghna Trivedi: We were able to identify five different adverse risk factors for TIPN. This included the receipt of Paclitaxel, having a higher stage or stage two or three disease, having a planned duration of taxane of greater than 12 weeks, having specific medical comorbidities and also having a Hispanic or non-white and Asian race.
So there were a variety of different demographic and clinical factors that could predict the risk of developing TIPN. And this model was able to differentiate nearly a fivefold increase in the risk of TIPN, between those who had three to five of these risk factors which were the highest quartile versus those with zero risk factors in the lowest quartile.
If we can identify those patients that are at highest risk for developing neuropathy, perhaps those are the ones that can be targeted for future prevention.
Erin: Through their study, Dr. Trivedi and her team met the fundamental challenge of standardizing symptoms and establishing the true prevalence of TIPN. This paved the way for a propensity model that can help predict which patients are at risk for developing neuropathy. All of this work lays the foundation for more reliable data collection and, ultimately, improved care for cancer patients not only in New York City, but globally.
The next step builds on these findings to drive a larger innovation: pursuing novel treatments and preventative measures to stop TIPN from developing in the first place. Right now, if a doctor finds that a patient is at risk, they work together to alter their treatment plan. Unfortunately, this can come with added risk for some patients for whom taxanes are crucial to their cancer therapy.
That’s why Dr. Trivedi is turning her focus toward using the findings from their ground-breaking risk assessment study to pinpoint a biomarker for TIPN. A biomarker will go one step further by helping physicians understand the mechanisms for why neuropathy develops. Dr. Trivedi recently received a prestigious R37 grant that is catapulting that research forward. The goal will be to improve first-line cancer treatments that mitigate negative effects and learn how to develop combination therapies that can reduce the use of taxanes and positively affect patient outcomes for those going through cancer treatment.
Erin: So tell me about the R37 grant that you were awarded to try to look for this possible biomarker for TIPN. I understand that you’re a Primary Investigator on the study.
Dr. Meghna Trivedi: In this grant we are using the samples that were collected to try and see, can we identify predictive biomarkers for neuropathy? And if these are identified, can these biomarkers enhance our clinical risk prediction model? Almost to develop an integrated risk prediction model using the biomarkers to better be able to discriminate between risk levels for, at the individual level.
Erin: Right. So by enhancing the risk prediction model and then using the biomarker, you're really kind of just, like, casting a wider net and being able to detect more individuals at earlier stages, potentially, who might develop peripheral neuropathy, which then leads to increased opportunities for intervention and intervention trials.
Dr. Meghna Trivedi: Right, exactly. So, can the biomarkers help us better define where someone falls on the spectrum of developing TIPN?
Erin: So this biomarker research could eventually be integrated into trials investigating potential interventions for TIPN. But for now, I’m curious, are you spearheading any clinical trials that are looking into some of these prevention and treatment strategies for these at-risk patients so that they can continue their course of care and effectively treat their cancer?
Dr. Meghna Trivedi: We do have a trial open at Columbia. And in this study we're actually looking at an intervention to try and prevent the development of taxane induced peripheral neuropathy. And so this is a trial that is looking at a cryo compression system in individuals who are undergoing treatment with a taxane based regimen. The idea is that either the hypothermia, the cold, or the compression part can be neuroprotective because it reduces the exposure of the peripheral nerves to the neurotoxic chemotherapy therapeutic agent.
And there have been some early studies that have demonstrated excitement for this approach. And so the hope of the trial is to try and identify if there is a change in the proportion of patients who develop a clinically meaningful chemotherapy induced peripheral neuropathy.
Additionally, you know, if we can identify the biomarkers that may give us a better understanding of what the mechanism is, and that can allow for hopefully future interventions or something like cryo compression to try and prevent and treat taxane induced peripheral neuropathy.
Erin: Well I'm excited to hear how these results pan out. I mean, these new preventative measures to treat TIPN could have a truly global impact on cancer care, especially since so many patients are treated with taxanes. And it seems like the resources and the collaboration with all your colleagues at Columbia really set you up to push cutting edge work like this forward, to improve the lives of patients, not just in New York, but also around the country. How do you feel that NewYork-Presbyterian and Columbia helps you to achieve this impactful research?
Dr. Meghna Trivedi: We have an amazing clinical research staff here at NYP Columbia that really help us carry out this research. We're so fortunate to have amazing collaborators through all of the different schools at Columbia, right?
Within the Mailman School of Public Health and the medical school. I think we're very fortunate to have such a large network of research collaborators through the NYP and Columbia system. I think that all of the support that we get through the institute allows us to carry out these multi-site studies with our collaborators at other institutions as well.
Erin: Well it has been so inspiring to chat with you and hear about all of this incredible research that you have achieved so far and currently have, you know, in the works. And I thank you so much for taking the time.
Dr. Meghna Trivedi: Yeah, thank you again for the invitation. The pleasure is mine.
Erin: Big thanks to Dr. Meghna Trivedi for taking the time to share how her pioneering work on chemotherapy induced peripheral neuropathy and genetics education could lead to improved outcomes and quality of life for cancer patients everywhere.
I’m Erin Welsh.
Advances in Care is a production of NewYork-Presbyterian Hospital. As a reminder, the views shared on this podcast solely reflect the expertise and experience of our guests. To listen to more episodes of Advances in Care, be sure to follow and subscribe on Apple Podcasts, Spotify, or wherever you get your podcasts. And to learn more about the latest medical innovations from the pioneering physicians at NewYork-Presbyterian, go to nyp.org/advances.