About

Marcia Simpson Brose, MD PhD, is an Emeritus Professor and the Chief of Otorhinolaryngology: Head and Neck Surgery at the University of Pennsylvania. She holds a B.A. in Biology from Amherst College, a Ph.D. in Genetics and Developmental Biology from Rockefeller University, and an M.D. from Cornell University Medical College. Dr. Brose has a distinguished career focused on thyroid cancer oncology and personalized cancer care, with significant contributions to the development of treatments for advanced thyroid cancer and solid tumors with rare genetic changes. She has been the Director of the Thyroid Cancer Therapeutics Program for over eight years and was appointed the Director of the Center for Rare Cancers and Personalized Therapy at the Abramson Cancer Center in 2015. Her research involves identifying novel treatments through genetic and molecular studies of tumor tissue, and she runs a clinical research unit and laboratory dedicated to this work. Dr. Brose is recognized as a pioneer in her field, leading pivotal international clinical trials that have resulted in FDA approvals for new therapies, and she is widely regarded as an international leader in thyroid cancer oncology. She also actively mentors medical students, residents, fellows, and post-doctoral researchers.

Research topics

• Medicine
• Internal medicine
• Oncology
• Cancer research
• Gastroenterology

Selected publications

• Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer after prior vascular endothelial growth factor receptor-targeted therapy (COSMIC-311): outcomes by BRAF status

  Frontiers in Oncology · 2026-03-04

  articleOpen access1st authorCorresponding

  Background Cabozantinib is approved for previously treated radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) based on improved progression-free survival (PFS) versus placebo in the COSMIC-311 study. The BRAF V600E mutation is common in DTC and is associated with poor prognosis. This planned exploratory analysis of COSMIC-311 reports outcomes by BRAF status. Methods In this exploratory analysis, outcomes by BRAF wt (wild-type) or BRAF V600E status were evaluated in the COSMIC-311 phase 3 study in patients with RAIR-DTC who had previously received lenvatinib and/or sorafenib. Results BRAF status was available for 106 of 258 patients enrolled in COSMIC-311; of these, 74 had BRAF wt and 27 had BRAF V600E . Cabozantinib prolonged PFS versus placebo in both the BRAF wt (hazard ratio [HR] 0.23 [95% CI: 0.12–0.44]; median PFS, 11.1 versus 1.9 months) and BRAF V600E (HR 0.15 [95% CI: 0.04–0.59]; median PFS, 9.2 versus 1.9 months) subgroups. While no responses were observed with placebo in both BRAF subgroups, objective response rates (ORRs) of 11% and 18% were observed with cabozantinib in the BRAF wt and BRAF V600E subgroups, respectively. Among patients treated with cabozantinib, 68% of the BRAF wt group and 53% of the BRAF V600E group reported grade 3/4 treatment-emergent adverse events; the incidences were 17% and 50% in the corresponding groups treated with placebo. Conclusions In this subgroup analysis of COSMIC-311, cabozantinib improved PFS and ORR versus placebo irrespective of BRAF mutation status. Thus, cabozantinib is an efficacious treatment option with a manageable safety profile for previously treated patients with RAIR-DTC, including those with BRAF V600E .

  PublisherOA PDFDOI

• Efficacy and safety of larotrectinib in patients with TRK fusion thyroid carcinoma: An updated analysis.

  Journal of Clinical Oncology · 2025-05-28

  article1st authorCorresponding

  6094 Background: NTRK gene fusions are oncogenic drivers in various tumor types, including thyroid carcinoma (TC). Larotrectinib (laro) is the first-in-class, highly selective, central nervous system-active TRK inhibitor, approved for tumor-agnostic use in patients (pts) with TRK fusion cancer. Here, we report updated long-term efficacy and safety data in pts with TRK fusion TC treated with laro. Methods: Pts with TRK fusion TC enrolled in 3 laro clinical trials (NCT02576431, NCT02122913, NCT02637687) were included. Laro was administered at 100 mg twice daily (BID) to adults; 2 pediatric pts received 100 mg/m 2 BID (maximum dose 100 mg BID). Responses were independent review committee-assessed per RECIST v1.1. Data cutoff: July 20, 2024. Results: At data cutoff, 31 pts were enrolled; 24 (77%) had differentiated TC (DTC) and 7 (23%) had anaplastic TC (ATC). Median age was 60 years (range 6–80). Median time since initial cancer diagnosis was 5 years (range 0–46). Seventeen pts (55%) were systemic treatment-naïve in the metastatic/unresectable setting, 6 (19%) received 2 or more prior therapies, and 24 (77%) received prior radioiodine. All NTRK gene fusions were identified by next-generation sequencing. Overall response rate (ORR) was 65% (95% confidence interval [CI] 45–81): 3 (10%) complete responses, 17 (55%) partial responses (PR), 5 (16%) stable disease (SD), 4 (13%) progressive disease (PD), and 2 (6%) not evaluable. For pts classified as DTC, ORR was 79% (95% CI 58–93). For pts classified as ATC, ORR was 14% (95% CI 0–58). Three (10%) pts had poorly differentiated TC, 1 classified as DTC (PR) and 2 as ATC (1 SD for >36 months and 1 PD). Median time to response for all pts was 1.9 months (range 1.6–16.2). Median duration of response, progression-free survival, and overall survival (OS) were 35 months (95% CI 19–not estimable [NE]), 39 months (95% CI 17–NE), and not reached (NR; 95% CI 28–NE), respectively, at median follow-ups of 48, 42, and 68 months. Median OS was NR (95% CI 56–NE) in DTC and 9 months (95% CI 3–NE) in ATC. The 6-year OS rate for all pts was 60% (95% CI 41–79). The 6-year OS rate was 71% (95% CI 50–91) for pts with DTC and 17% (95% CI 0–46) for pts with ATC. Median duration of treatment was 31 months (range 1–88). At data cutoff, 7 (23%) pts remained on treatment, 5 of whom had disease control. Treatment-related adverse events (TRAEs) were predominantly Grade 1/2. Grade 3/4 TRAEs were reported in 5 (16%) pts. There were no discontinuations due to TRAEs. Conclusions: Laro demonstrates rapid and durable responses, extended survival, and a favorable safety profile in pts with TRK fusion DTC. Limited single-agent activity is observed in pts with ATC. This supports the use of a TRK inhibitor to treat TRK fusion DTC and the importance of testing for NTRK gene fusions in patients with advanced TC needing systemic therapy. Clinical trial information: NCT02576431 , NCT02122913 , NCT02637687 .

  PublisherDOI

• Larotrectinib Compared With Real-World Non–Tropomyosin Receptor Kinase Inhibitor Therapies in Patients With Tropomyosin Receptor Kinase Fusion Cancer

  JCO Precision Oncology · 2025-04-01 · 2 citations

  articleOpen access1st authorCorresponding

  PURPOSE Neurotrophic tyrosine receptor kinase gene fusions are oncogenic drivers of various solid tumors. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor approved for patients with TRK fusion cancer on the basis of single-arm trials. This study was a matched comparative effectiveness study of larotrectinib in clinical trials versus standard of care (SOC) in the real-world (RW) setting. METHODS Adult patients with advanced/metastatic TRK fusion non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, or salivary gland carcinoma were included. Deduplicated data from RW patients were from US and ex-US data sources. Patients in the larotrectinib cohort (pooled data from three trials, ClinicalTrials.gov identifiers: NCT02122913 , NCT02576431 , and NCT02637687 ) were matched 1:1 to RW patients on the basis of tumor type and line of therapy (LOT). A propensity score (weighting) model was used to balance key characteristics between cohorts. The primary outcome was overall survival (OS). RESULTS In total, 164 patients were matched 1:1 on tumor type and LOT (82 in each cohort). Balance in the baseline covariates was achieved after weighting. Larotrectinib-treated patients had longer OS (median, not reached [NR] v 37.2 months; hazard ratio [HR], 0.44 [95% CI, 0.23 to 0.83]), time to next treatment (median, NR v 10.6 months; HR, 0.22 [95% CI, 0.13 to 0.38]), duration of therapy (median, 30.8 v 3.4 months; HR, 0.23 [95% CI, 0.15 to 0.33]), and progression-free survival (median, 36.8 v 5.2 months; HR, 0.29 [95% CI, 0.18 to 0.46]) compared with RW patients after propensity score weighting. CONCLUSION In TRK fusion cancers, treatment with larotrectinib was associated with longer OS and prolonged time to event compared with SOC in all categories measured. These RW data provide context to support larotrectinib effectiveness in this population.

  PublisherDOI

• Patient-Reported Tolerability of Selpercatinib Compared to Cabozantinib/Vandetanib: A Secondary Analysis of the LIBRETTO-531 Randomized-Controlled Trial in <i>RET</i> -Mutant Medullary Thyroid Cancer

  Thyroid · 2025-10-01 · 4 citations

  articleOpen accessSenior author

  Background: Progression-free survival (PFS) may not fully capture the impact of treatment on patients, especially in cancers with longer natural histories and thus, could be complemented by robust measures of patient-reported tolerability (PRT). We report the use of a novel, quantifiable PRT metric as a multiplicity-controlled endpoint to support regulatory and clinical decision-making for selpercatinib use. Comparative PRT was assessed in LIBRETTO-531 (NCT04211337), a randomized phase 3 trial of selpercatinib versus vandetanib/cabozantinib (control) in advanced RET -mutant medullary thyroid cancer (MTC). Patients and Methods: Patients were self-administered the single Functional Assessment of Cancer Therapy item GP5: “I am bothered by side effects” weekly, and scores were dichotomized into “low” (0–2) and “high” (3–4) side-effect burden. PRT measured the proportion of time on treatment (PTT) with “high” side-effect burden for each patient. Comparative PRT was tested at a two-sided significance level of 0.05, conditional on achieving significance for efficacy endpoints. Complementary patient-reported outcomes included health-related quality of life (HRQoL) and symptomatic adverse events self-administered at baseline and at different intervals post-baseline during treatment period. Results: In the tolerability evaluable population (N = 242; selpercatinib n = 161 and control n = 81 [56 received cabozantinib, 25 received vandetanib]), patients on selpercatinib had significantly better PRT with lower PTT with “high side-effect burden” than control (8% vs. 24%, p &lt; 0.0001). Post-baseline compliance rates for PRO questionnaires were generally greater than 80% in both treatment groups. Patients on selpercatinib reported significantly less PTT with HRQoL impairment across physical (36% vs. 52%), role (2% vs. 11%), cognitive (4% vs. 8%), emotional (6% vs. 11%), and social (2% vs. 8%) function (all p &lt; 0.01); and significantly less PTT with severe diarrhea (5% vs. 38%), fatigue (6% vs. 21%), taste change (3% vs. 15%), decreased appetite (2% vs. 15%), and hand-foot syndrome (2% vs. 9%) (all p &lt; 0.001). Conclusion: This study demonstrated superior PRT for selpercatinib compared with control in patients with RET -mutant MTC, further supporting selpercatinib use as the first-line treatment for patients with advanced RET -mutant MTC. Comparative PRT deserves further adoption as a complement to traditional endpoints in future randomized-controlled trials.

  PublisherDOI

• Well-Differentiated Lung Neuroendocrine Tumor Masquerading as Metastatic Medullary Thyroid Cancer

  JCEM Case Reports · 2025-07-14

  articleOpen access

  Typical carcinoid tumors, or low-grade neuroendocrine tumors (NETs), are a rare class of neoplasms that share histopathological characteristics with other NETs like medullary thyroid cancer (MTC). Here, we report an 85-year-old woman with a history of left hemithyroidectomy in the 1980s (pathology not available) and right-sided multinodular goiter biopsied as benign, initially misdiagnosed with metastatic MTC based on lung nodule biopsy staining for calcitonin. The lung nodule was surgically removed and shown to be a well-differentiated lung NET. This case demonstrates the diagnostic challenges of integrating cytopathological findings, such as calcitonin staining, with the overall clinical scenario to arrive at an accurate diagnosis.

  PublisherOA PDFDOI

• Durability of Response With Selpercatinib in Patients With <i>RET</i>-Activated Thyroid Cancer: Long-Term Safety and Efficacy From LIBRETTO-001

  Journal of Clinical Oncology · 2024-08-02 · 39 citations

  articleOpen access

  Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. LIBRETTO-001 is a registrational phase I/II, single-arm, open-label study of selpercatinib in patients with RET (REarranged during Transfection)-activated cancers (ClinicalTrials.gov identifier: NCT03157128 ). We present long-term safety and efficacy from LIBRETTO-001 in patients with RET-mutant medullary thyroid cancer (MTC; n = 324) and RET fusion-positive thyroid cancer encompassing different histological subtypes (TC; n = 66). At the data cutoff of January 2023, the objective response rate was 82.5% among patients with cabozantinib/vandetanib-naïve MTC and 95.8% among patients with treatment-naïve TC. At a median follow-up time of 42.4 and 44.0 months in patients with cabozantinib/vandetanib-naïve and pretreated MTC, the median progression-free survival (PFS) was not reached and 41.4 months, respectively. At a median follow-up time of 24.9 and 30.4 months in patients with treatment-naïve and pretreated TC, the median PFS was not reached and 27.4 months, respectively. Three-year PFS rates were 75.2% and 87.3% among patients with cabozantinib/vandetanib-naïve MTC and treatment-naïve TC, respectively. Median PFS was similar to median duration of response for each patient group. The safety profile of selpercatinib was consistent with previous reports. With an additional follow-up of 37 months and 228 more patients from the last disclosure, selpercatinib continued to provide durable and robust responses in treatment-naïve and previously treated patients with RET-mutant MTC and RET fusion-positive TC.

  PublisherDOI

• A plain language summary looking at how well larotrectinib works and how safe it is for people with TRK fusion-positive thyroid cancer

  Future Oncology · 2024-11-29 · 1 citations

  articleOpen accessSenior author

  What is this summary about? This is a summary of a publication on TRK fusion-positive thyroid cancer. TRK fusion-positive means that each participant’s cancer had a specific change in the tumor’s genes, called an NTRK gene fusion, that caused their cancer. The 2 main types of TRK fusion-positive thyroid cancers that the researchers looked at in this study were differentiated thyroid cancer (DTC) and anaplastic thyroid cancer (ATC). The researchers wanted to know whether the study drug, larotrectinib, could shrink the participants’ cancers and what medical issues happened during treatment that the researchers thought could be related to larotrectinib. What were the main results reported by the researchers? Researchers found that, among the participants with TRK fusion-positive DTC who took larotrectinib, 86% (18 out of 21) of the participants had their tumors respond to treatment. This means their tumors shrank by over 30% or disappeared completely. 100% of the participants whose tumors responded to treatment continued to respond for 12 months (1 year). Researchers also found that, among the participants with TRK fusion-positive ATC who took larotrectinib, 29% (2 out of 7) of the participants had their tumors respond to treatment. 1 of the 2 participants whose tumors responded to treatment continued to respond for 12 months (1 year). Among all of the participants who took larotrectinib, researchers found that 90% developed medical issues, also called adverse events, that the researchers thought might be possibly related to larotrectinib. This was 26 out of 29 participants. Most of these adverse events were classified as mild. What do the results mean? Larotrectinib could be a treatment option for people with TRK fusion-positive differentiated thyroid cancer (DTC). It is not as effective in people with anaplastic thyroid cancer (ATC) and is likely not an appropriate treatment for ATC. Further research is needed to understand why larotrectinib is not as effective in people with ATC. Who sponsored this study? This study focused on 3 trials that were sponsored by Bayer Healthcare and Loxo Oncology, Inc., a wholly owned subsidiary (part or sub-company) of Eli Lilly and Company.

  PublisherOA PDFDOI

• Vandetanib in locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine therapy

  Endocrine Related Cancer · 2024-06-03 · 11 citations

  articleOpen access1st authorCorresponding

  The VERIFY study aimed to determine the efficacy of vandetanib in patients with differentiated thyroid cancer (DTC) that is either locally advanced or metastatic and refractory to radioiodine (RAI) therapy. Specifically, VERIFY is a randomized, double-blind, multicenter phase III trial aimed to determine the efficacy and safety of vandetanib in tyrosine kinase inhibitor-naive patients with locally advanced or metastatic RAI-refractory DTC with documented progression (NCT01876784). Patients were randomized 1:1 to vandetanib or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included best objective response rate, overall survival (OS), safety, and tolerability. Patients continued to receive randomized treatment until disease progression or for as long as they were receiving clinical benefit unless criteria for treatment discontinuation were met. Following randomization, 117 patients received vandetanib, and 118 patients received a placebo. Median PFS was 10.0 months in the vandetanib group and 5.7 months in the placebo group (hazard ratio: 0.75; 95% CI: 0.55-1.03; P = 0.080). OS was not significantly different between treatment arms. Common Terminology Criteria for Adverse Events (CTCAE) of grade ≥3 were reported in 55.6% of patients in the vandetanib arm and 25.4% in the placebo arm. Thirty-three deaths (28.2%; one related to study treatment) occurred in the vandetanib arm compared with 16 deaths (13.6%; two related to treatment) in the placebo arm. No statistically significant improvement was observed in PFS in treatment versus placebo in patients with locally advanced or metastatic, RAI-refractory DTC. Moreover, active treatment was associated with more adverse events and more deaths than placebo, though the difference in OS was not statistically significant.

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• Evaluation of potential biomarkers for lenvatinib plus pembrolizumab among patients with advanced endometrial cancer: results from Study 111/KEYNOTE-146

  Journal for ImmunoTherapy of Cancer · 2024-01-01 · 17 citations

  articleOpen access

  Background Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 ( NCT02501096 ). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest. Methods Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell–inflamed gene expression profile (Tcell inf GEP) and 11 other gene signatures were evaluated by RNA sequencing. TMB, hotspot mutations in PIK3CA (oncogene), and deleterious mutations in PTEN and TP53 (tumor suppressor genes) were evaluated by whole-exome sequencing (WES). Results 93 and 79 patients were included in the RNA-sequencing-evaluable and WES-evaluable populations, respectively. No statistically significant associations were observed between any of the RNA-sequencing signature scores and objective response rate or progression-free survival. Area under the receiver operating characteristic curve values for response ranged from 0.39 to 0.54; all 95% CIs included 0.50. Responses were seen regardless of TMB (≥175 or &lt;175 mutations/exome) and mutation status. There were no correlations between Tcell inf GEP and TMB, Tcell inf GEP and microvessel density (MVD), or MVD and TMB. Conclusions This analysis demonstrated efficacy for lenvatinib plus pembrolizumab regardless of biomarker status. Results from this study do not support clinical utility of the evaluated biomarkers. Further investigation of biomarkers for this regimen is warranted. Trial registration number NCT02501096 .

  PublisherOA PDFDOI

• Patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) with BRAF V600E and/or K601E mutation status: A real-world view of effectiveness of lenvatinib monotherapy.

  Journal of Clinical Oncology · 2024-06-01 · 3 citations

  articleSenior author

  6098 Background: Lenvatinib was approved for the treatment of patients RAI-R DTC in the United States (US) in 2015, and the treatment landscape has evolved with agents targeting specific driver mutations. We assessed real-world clinical effectiveness of first line therapy with lenvatinib in patients with BRAF-mutated tumors, wild-type (WT) tumors, and patients who have not been tested for BRAF mutations (BRAF untested tumors). Methods: A retrospective chart review of RAI-R DTC patients in the US who initiated first-line lenvatinib monotherapy between February 13, 2015, and September 30, 2020. Data, including a boosted cohort of patients with BRAF-mutated tumors collected in late 2023, were abstracted from patients’ electronic health records and were de-identified. Descriptive analyses were conducted in patient cohorts with BRAF V600E and/or K601E mutated tumors, wild-type (WT) tumors, and BRAF untested tumors. Best response in first-line therapy was captured, real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were assessed using Kaplan-Meier methods. Results: Of the 361 patients reviewed, 185 had records showing BRAF mutational status testing. 89 had BRAF V600E and/or K601E mutated tumors, 96 had WT tumors. 176 patients did not have BRAF mutational assessment. Of all subjects, 73.7% were White/Caucasian, 15.2% were African American, and 16.8% were Hispanic/Latino; 27.1% had ECOG performance status ≥2. The median follow-up times for each cohort were 30.0, 18.7 and 18.0 months, showing the longer follow up period for the BRAF-mutated cohort boost. Kaplan-Meier estimation for lenvatinib treatment discontinuation for the three cohorts at 24-months were as shown in the table below. Provider-reported overall response rate (complete or partial response) was 76.4%, 75.0% and 69.3% respectively. The estimated 24-month rwPFS rates (95% CI) were 74.1% (62.2%-82.8%), 61.7% (49.6%-71.8%), and 69.8% (60.9%-77.0%) respectively. Median rwOS was not reached for patients with BRAF-mutated and WT tumors, median OS was 54.2 months for BRAF untested tumors. Estimated rwOS rates at 12- and 48-months were 93.2% (85.4%-96.9%) and 83.9% (73.3%-90.3%) in BRAF-mutated patients, 90.6% (82.8%-95.0%) and 68.5% (53.4%-79.6%) in WT patients, and 90.2% (84.7%-93.8%) and 72.5% (61.6%-80.7%) in BRAF untested patients respectively. Conclusions: In this US real-world experience, the effectiveness of lenvatinib is consistent across a diverse cohort of RAI-R DTC patients with BRAF-mutated, WT, and BRAF untested tumors. This has implications for the first-line use of lenvatinib in BRAF mutated patients. [Table: see text]

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Recent grants

• NIH Grant K08CA090431

  NIH · $689k · 2009

Frequent coauthors

• Lori J. Wirth

  Massachusetts General Hospital

  92 shared

• Francis P. Worden

  54 shared

• Martin Schlumberger

  53 shared

• Mats Holmberg

  50 shared

• Shivaani Kummar

  Oregon Health & Science University

  48 shared

• Ulrik Lassen

  Copenhagen University Hospital

  47 shared

• Alexander Drilon

  46 shared

• Matthew H. Taylor

  46 shared