Tan, Winston

Abstract Background and Objective Management of von Hippel–Lindau (VHL) disease is challenging due to multisystem involvement and limited systemic treatment options. Belzutifan has shown promising efficacy in clinical trials; however, real-world data remain limited. We aimed to evaluate its effectiveness and safety in a real-world cohort. Methods We conducted a retrospective study of 59 patients with VHL disease treated with belzutifan between August 2021 and January 2026. Objective response rates (ORR) for renal cell carcinoma (RCC), central nervous system hemangioblastomas (CNS HB), and pancreatic neuroendocrine tumors (pNET) were assessed by an independent radiologist. Retinal hemangioblastoma outcomes were evaluated through ophthalmology records by chart review. Results Median follow-up was 29 months. ORR was 27.6%, 39.6%, and 85.7% for RCC, CNS HB, and pNET, respectively. Among 13 patients with retinal hemangioblastomas (20 eyes), 17 eyes (85%) showed improvement. At data cutoff, 47 patients (79.6%) remained on treatment, while 12 (20.3%) discontinued (7 due to adverse events, 3 to disease progression, and 2 to other reasons). The most common adverse event was anemia (86.4%). Grade ≥3 events occurred in 10 patients (16.9%). The procedure rate per patient-year decreased from 0.35 in the 3 years prior to treatment to 0.08 during follow-up (Incidence Rate Ratio, 0.23; 95% CI, 0.12–0.47; P < 0.001) Conclusions Belzutifan demonstrated efficacy across VHL-associated lesions, with favorable safety profile. Most adverse events were grade 1–2. A reduction in procedure rate was observed after treatment initiation.

Abstract Background: Melanoma brain metastases (MBM) represent a biologically distinct and clinically aggressive subset of melanoma. Comprehensive molecular characterization focused on intracranial disease remains limited. We aimed to define the genomic landscape of MBM and compare these findings with public melanoma datasets. Methods: We retrospectively identified 166 patients with histologically confirmed MBM across Mayo Clinic tri-sites (2011-2025). Molecular testing was performed in 123 patients (74.1%). Comprehensive next-generation sequencing (NGS; ≥300-gene platforms including Tempus, FoundationOne, Caris, NeoGenomics, and MayoComplete Solid Tumor Panel) was available in 41 patients (24.7%). Intermediate-depth profiling using the MayoComplete Melanoma Panel (17 genes) was performed in 21 patients (12.7%), and a targeted 5-gene melanoma driver panel (BRAF, NRAS, KIT, GNAQ, GNA11) in 52 patients (31.3%). cfDNA-based NGS was available in 12 patients (7.2%). Genomic alterations were summarized and benchmarked against TCGA-SKCM and MSK-IMPACT datasets via cBioPortal. We considered assay heterogeneity, as Mayo panels varied in sequencing depth and CNV coverage, and hybrid-capture platforms often under-detect TERT promoter hotspots. Results: Patients had a median age of 67 years, and 63% were male. BRAF mutations occurred in 48.8% (BRAF V600E/K 41.6%; non-V600 7.2%). Additional MAPK alterations included NRAS (17.5%), KIT (5.4%), GNAQ (1.2%), and GNA11 (0.6%). In the comprehensive NGS subset, tumor-suppressor alterations included CDKN2A (17.5%), PTEN (7.8%), NF1 (9.0%), TP53 (8.4%), and TERT promoter mutations (22.9%). Median TMB was 11.55 mut/Mb (IQR 5.0-25.5). Co-alterations included BRAF+CDKN2A (7.2%), BRAF+PTEN (4.2%), NRAS+CDKN2A (4.2%), NRAS+PTEN (1.2%), and CDKN2A+PTEN (3.6%); overall, 18.1% harbored MAPK driver + tumor-suppressor co-alterations. Compared with TCGA and MSK cohorts, MBM showed similar MAPK driver frequencies but fewer MAPK + tumor-suppressor co-alterations and lower CDKN2A, PTEN, and TP53 disruption, alongside a more prevalent of TERT promoter mutations (22.9% vs 7% and 2.1%), which may partly reflect coverage differences. Conclusion: MBM exhibit a distinct genomic profile characterized by reduced tumor-suppressor loss, fewer MAPK-tumor-suppressor co-alterations, and higher prevalence of TERT promoter mutations. While assay heterogeneity limits direct cross-cohort comparisons, these patterns suggest potentially distinct biological features of intracranial melanoma and underscore the need for harmonized, MBM-specific molecular studies to guide therapeutic development. Citation Format: Dina Elantably, Joseph B. Parker, Jakob Hamilton, Ahmed Abdelhakeem, Oluwatayo Adeoye, Saivaishnavi Kamatham, Winston Tan, Arkadiusz Z. Dudek, Anastasios Dimou, Matthew S. Block, Robert McWilliams, Svetomir Markovic, Mahesh Seetharam, Roxana Dronca, Ruqin Chen. Genomic landscape of melanoma brain metastases: Real-world analysis and comparison with public melanoma cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2107.

465 Background: Molecular testing is crucial in advancing precision medicine, enabling oncologists to tailor targeted treatment strategies for cancer patients (pts). The National Comprehensive Cancer Network (NCCN) and ASCO guidelines recommend comprehensive biomarker testing for pts with mPC. However, compliance can vary considerably among institutions. This study aimed to assess current practices of molecular testing in diverse healthcare settings across the state of Florida and identify opportunities for improvement to optimize outcomes for pts diagnosed with mPC. Methods: We conducted a detailed 12-question survey, distributed both electronically and in-person to evaluate the molecular testing practices of healthcare providers throughout the state. The survey assessed multiple parameters including adherence to testing, reviewing test results to guide treatment decisions, and the availability of different supportive resources in biomarker testing. This initiative was executed in partnership with the Florida Society of Clinical Oncology and industry partners. Results: A total of 40 responses were collected from 11 institutions in Florida, including 5 academic centers and 6 community-based hospitals. Notably, 22.5% of respondents reported that their institutions either do not fully comply with NCCN guidelines or lack protocols to identify eligible pts and 67.5% stated they are responsible for their own biomarker education and updates. Only 56.4% consistently review molecular testing results during disease progression to guide treatment decisions. Nearly all institutions lack clinical decision support tools in the electronic medical records (EMR) to support testing, and 82.5% receive biomarker results outside the EMR. Additionally, 38.5% lack a standard process for obtaining prior authorization for testing. Furthermore, 38.5% lack a multidisciplinary review process for genetic test results, and 76.3% reported that their biomarker testing process does not involve geneticists or genetic counselors. Conclusions: Our study identified critical gaps in adherence to biomarker testing guidelines with many practices lacking decision support tools across healthcare institutions in Florida. Potential areas for improvement include better standardization of result integration into EMR, targeted educational initiatives, and stronger multidisciplinary collaborations. The implementation of these measures aims to improve the quality of care and outcomes for pts with mPC.

LBA1551 Background: Traditional cancer therapy is primarily delivered in clinical settings, imposing logistical, emotional, and financial burdens, particularly on rural and underserved patients. While international studies have demonstrated the safety of home-based chemotherapy, no randomized U.S. trials have evaluated this approach. Mayo Clinic’s CCBW program aims to expand access to high-quality cancer care by providing in-home cancer treatment, lab testing, telemedicine, remote patient monitoring, command center and paramedic support. This pragmatic randomized controlled trial evaluates feasibility and impact of home-based versus in-clinic cancer directed therapy on patient preference, acceptability, safety, and patient-reported outcomes. Methods: Adult patients (ECOG 0-2) receiving chemotherapy or hormonal therapy at Mayo Clinic Florida were randomized 1:1 after confirmation of treatment tolerance in clinic to receive (1) home-based care for 24 weeks or (2) in-clinic care for 8 weeks followed by home-based care for 16 weeks. Target accrual is 200 patients. A planned interim analysis after 50 enrollments assessed accrual, data completeness, technical challenges, safety, and study outcomes. The primary endpoint is patient ratings of their overall cancer care experience (0–10 scale, CAHPS Cancer Care Survey) at 8 weeks. 200 patients provide 80% power to detect a 0.45 standard deviation difference in mean ratings between arms with a 2-sided 2-sample t-test (α=0.05) and 20% missing data rate. Secondary endpoints are patient preference, comfort with home infusions, treatment worthwhileness, functional/symptom assessments (EORTC QLQ-F17, PRO-CTCAE, GP5), grade ≥3 AEs, hospitalizations, and overall survival. Cost is a tertiary endpoint. The trial is IRB-approved (#23001719) and registered (NCT05969860). Results: Enrollment began 8/23/23. As of 2/21/25, 52 patients (26 per arm) were enrolled and 36 started protocol treatment. Common cancers were breast (38%), colorectal (21%), prostate (19%), and multiple myeloma (14%). 64% (28/44) of patients were female; 84% identified as White, 14% as Black, and 2% as multiple races. Median distance to clinic was 20 miles (range 2-66). After 8 weeks, patients in both arms rated their overall cancer care experience highly (mean [SD]=9.69 [0.85] versus 9.54 [0.66] for home-based vs. in-clinic care, n=26). After 24 weeks, 73% preferred home-based care, 18% had no preference, and 9% preferred in-clinic care; 100% felt comfortable with home infusions. No grade ≥3 AEs related to location of care have occurred. Conclusions: Early findings support the feasibility, safety, and high patient acceptability of home-based cancer therapy. No safety concerns related to care location were observed and most patients preferred home-based treatment. Ongoing accrual and analysis will assess clinical outcomes and cost implications. Clinical trial information: NCT05969860 .

TPS1657 Background: Cancer treatments are traditionally administered in clinical settings, which can isolate patients from their familiar environments and exacerbate physical, psychosocial, and financial burdens. Travel requirements further amplify these challenges, particularly for underserved populations. Studies indicate that patients prefer receiving care at home, and international models have demonstrated the safety of home-delivered chemotherapy since the 1990s; however, no U.S. clinical trial data exists. In response, Mayo Clinic has developed the Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) program, a distributed cancer care delivery model that expands access to quality cancer care by bringing it to the home environment, providing in-home cancer treatment, lab testing, telemedicine, and community paramedic support. This trial evaluates the safety, acceptability, and impact of home-based subcutaneous (SC) nivolumab (Nivo) administration compared to in-clinic treatment within the CCBW initiative. Methods: This open-label, single-arm trial evaluates the impact of SC Nivo administration location—home versus infusion center—on patient reported cancer care experience, patient-preferred treatment location, acceptability, safety, and patient-reported outcomes. Eligible adult patients (ECOG 0-1) receiving IV Nivo for an FDA-approved indication and residing within 75 miles of Mayo Clinic Florida will transition to SC Nivo, receiving two initial in-clinic cycles. If tolerated without injection reactions, four cycles will be administered at home before resuming in-clinic treatment. Exclusion criteria include concurrent investigational/standard treatments or contraindications to immunotherapy. Fifty patients will be enrolled, with an estimated 75% (n=38) providing cancer care ratings after 8 weeks in-clinic and 8 weeks at-home, offering 85% power to detect a mean difference in ratings of 0.50 standard deviations. The primary endpoint is within-patient change in cancer care rating (0–10 scale, CAHPS Cancer Care Survey) comparing 8 weeks of in-clinic vs. at-home care. Secondary endpoints include patient-preferred treatment location, comfort with home injections, safety (grade 3+ adverse events), function (EORTC QLQ-F17), symptoms (PRO-CTCAE), side effect impact (GP5), and healthcare utilization (ER visits, hospitalizations). Cost will be assessed as a tertiary endpoint. The trial has FDA approval (IND #170079), Mayo Clinic IRB approval (#23009663), and ClinicalTrials.gov registration (NCT06265285). Enrollment began in April 2024, with an expected accrual period of 24 months. To date, 10 patients have been enrolled, and final analysis is expected 2.5 years after trial activation. Clinical trial information: NCT06265285 .

9029 Background: Addressing guideline concordant FP and TPP with cancer is challenging, especially for OT. SIM, a well-known education tool, has not been traditionally used to teach these topics. As part of the hematology/oncology fellowship curriculum, we designed a SIM applying LSP to bridge this educational gap. Methods: Applying LSP of contrasting cases, elaboration, feedback, generation and just-in-time telling, chief OTs and faculty designed a SIM with 3 clinical scenarios (CS) and 3 standardized pts (SP): FP for a female pt hospitalized for acute lymphoblastic leukemia tx, FP for a male pt in clinic for germ cell tumor tx, and breast cancer tx for a pregnant pt in 2 nd trimester. OT received written educational materials (WEM) and attended a lecture 1 week and 1 day pre SIM, respectively. OT were split into 2 groups; 1 started in the FP CS and 1 in the TPP CS, and then they switched. To reduce cognitive overload, each OT participated in 1 of 2 FP CS: half in the female FP CS and half in the male. Faculty and chiefs led debriefing sessions after all CS. The FP debrief ended with a special “learner as a teacher” part, where OT who attended the female CS taught those from the male CS about their topic and vice versa. The SIM concluded with "take-home" points. Pre (after having WEM) and post SIM anonymous surveys and verbal feedback assessed OT comfort, perceptions, and knowledge. Results: A 3 hour SIM with 14 OT and 5 faculty was completed successfully. SIM ended with all OT verbally sharing a learning point and positive feedback. All OT filled pre and post SIM surveys. Pre SIM, 17% reported having prior FP education, and 42% had prior TPP education. However, only 8% and 25% felt adequately prepared for FP and TPP discussions, respectively. Post SIM survey showed major improvement in comfort and knowledge about FP and TPP (see table 1). 75% of OT favored a combination of SIM and learning by teaching over other SIM formats. 83% supported having a TPP lecture before SIM. 100% reported satisfaction with FP and TPP SIM’s quality and wanted similar activities in the future. 92% were satisfied with the learner as a teacher tool. 100% felt education about FP and TPP with cancer should be part of fellowship training. Moral/cultural concerns were discussed as possible challenges in FP education. Conclusions: The application of LSP through SIM significantly increased OTs’ comfort discussing FP and TPP with cancer, and objectively enhanced their knowledge on these topics compared to after reading WEM. The SIM was largely perceived as a successful activity to educate about challenging topics and should become part of fellowship curriculum. Pre SIM % Post SIM % Comfortable addressing FP 17 92 Comfortable addressing TPP 8 100 Correct answers about female FP 63 83 Correct answers about male FP 67 94 Correct answers about TPP with cancer 68 98

Background Clonal hematopoiesis (CH) is defined by somatic mutations in hematopoietic stem cells, often conferring a selection advantage based on clonal selection pressures. CH in DNA Damage Response and Repair (DDR, e.g. TP53, PPM1D) genes are frequent in individuals exposed to chemotherapy and radiation (chemo/XRT). In metastatic prostate cancer (mPC) patients, the prevalence of CH is estimated at 57% and is increased among those with prior exposure to chemo or XRT. In these patients, the use of radiotheranostics is becoming more prevalent and are now being tested in earlier lines of therapy. We have identified an increase in DDR-somatic variants post lutetium-177-PSMA, raising concern for long term hematologic safety. Here, we evaluate the spectrum of CH and CCUS (clonal cytopenias of undetermined significance) in mPC patients, prior to receiving radioisotope therapies. Methods We performed error corrected next-generation sequencing (NGS) on peripheral blood samples from 67 mPC patients enrolled in the Prostate Cancer Medically Optimized Genome Enhanced Therapy Study (PROMOTE) study (NCT #01953640). All patients enrolled also had whole exome sequencing (WES) performed on initial metastatic biopsies and on whole blood for germline genotyping. Somatic variants with a variant allele fraction (VAF) ≥0.5% were considered as CH, using standard bioinformatic variant calling algorithms. Results The median age at NGS was 74.4 years (range, 58.4-92.3). While all patients received androgen deprivation therapy (ADT) +/- androgen receptor pathway inhibitor (ARPI), 67.2% (n=45, pelvic XRT- 35, palliative XRT- 10) received prior XRT and 3% (n=2) received prior docetaxel. No patients in this cohort received prior platinum or PARP inhibitor. Of those treated with XRT or chemo, the median time from first exposure to CH sample collection was 4.1yrs (range, 0.12-29.6) and 2.3yrs (range, 0.6-4.0), respectively. Of the 67 patients, we identified a total of 111 pathogenic variants in 59 (88.1%) patients. We compared our NGS data to the germline data and tumor for each patient (All samples obtained at the same time point; Wang et al 2018). Our analysis excluded 2 ATM variants likely to be germline, and 1 TP53 variant likely to be tumor-derived. Each patient had at least one somatic variant, with a median of 2 variants (range, 1-6The median CH VAF was 1.8% (range, 0.5-50.2) with 91.0% of alterations detected at a VAF of <10%. Specific somatic variants, presence/absence of CH, number of variants, nor VAF was associated with age, prior chemo, or XRT exposures. At time of NGS, 54% of patients were anemic (hgb <13g/dL), 7% were thrombocytopenic (platelets <135 x109), 6% were leukopenic (WBC <3 x 109), and no patients were neutropenic (ANC <1 x109). Persistent cytopenias, lasting >3months, were present in 25% (n=17) of patients; however, bone marrow biopsies (BMB) were performed only in 6% (n=4). Three (75%) of these 4 patients had mPC infiltration in the BM, and 1 (25%) had mild dysplasia not meeting criteria for MDS but meeting criteria for CCUS (CHEK2 somatic variant). At last follow-up, there were no patients formally diagnosed to have myeloid neoplasm (MN). Median overall survival (OS) from prostate cancer diagnosis was 8.6yrs (range, 1.4-28.4). With a median follow up of 2.2yrs (range 0.1-10.8) after CH testing, 3.0% (n=2) were alive, with most deaths occurring due to mPC. The presence of CH did not impact overall survival (OS), however, presence of cytopenias at the time of NGS testing was associated with worse outcomes (median OS 2.5yrs vs 1.2 yrs., p=0.025). Conclusions We define the landscape of CH mutations in mPC patients predominantly treated with ADT/ARPI and XRT, demonstrating that DNMT3A, TET2, PPM1D and ASXL1 are frequently mutated (88%) and largely subclonal (91% with VAF ≤10%). While 25% of these patients had cytopenias, with cytopenias negatively impacting survival, due to inadequate BM biopsy work up, the true prevalence of CCUS and MN could not be estimated. Given the advancement of genotoxic therapies and the high prevalence of subclonal CH in mPC, future studies investigating CH as a predictive biomarker of hematological dysfunction are much needed.

Melanoma is the deadliest form of skin cancer. The median age at diagnosis is 66. While most patients are treated with immunotherapy, the use of targeted therapy is a valid alternative for patients whose tumors harbor a BRAF or c-KIT driver mutation. These agents, while effective, come with a variety of side effects which limit their use, especially in older patients. We sought to assess the efficacy and toxicity of these agents in older melanoma patients. Melanoma patients over 65 treated with BRAF/MEK or c-KIT inhibitors were retrospectively identified, and their data were analyzed for treatment efficacy and toxicity. All data were compared using the Chi-square test for categorical comparisons and the Kruskal–Wallis method for median comparisons. One hundred and sixteen patients were identified. One hundred and six patients were treated with BRAF/MEK inhibitors. The assessed response rate (RR) was 83% and was comparable across different subgroups, including advanced line patients and those with a more aggressive disease. The median progression free survival (PFS) was 7.9 months, and the median overall survival (OS) was 15.7 months. Twenty-seven percent experienced grade 3–4 toxicity leading to a 24% treatment discontinuation rate. Another 10 patients were treated with the c-KIT inhibitor imatinib, for whom the assessed RR was 55%. The median PFS was 4.3 months, and the median OS was 22.6 months. Forty percent needed dose reductions, yet none had to stop treatment due to adverse effects. The use of targeted therapy in older patients is effective yet challenging due to toxicity. Deploying mitigation strategies can help maximizing their usefulness.

4574 Background: Mutations of COMPASS-related proteins KMT2D, KMT2C, and KDM6A are observed in 66% of advanced urothelial carcinomas (UC). In vivo, the administration of tazemetostat, an enzymatic EZH2 inhibitor (EZH2i), reduced tumor burden and enhanced the immune response in animal models of UC. We hypothesized that tazemetostat might improve response to immunotherapy in advanced UC. Methods: ETCTN 10183 (NCT03854474) is a multicenter pilot study evaluating the safety and efficacy of tazemetostat 800 mg BID+ pembrolizumab 200 mg given every three weeks for up to two years in patients (pts) with platinum-refractory (Arm A) or cisplatin/chemo-ineligible advanced UC (Arm B). The primary objective was to identify the recommended phase two dose (RP2D) of tazemetostat in combination with pembrolizumab. Secondary objectives included safety, response rate, and progression-free survival. Translational objectives included determining tumor mutational burden in COMPASS-related genes, tumor subtyping, TCR clonality, T cell infiltration, and PDL-1 expression. Results: There were no dose-limiting toxicities in the safety lead-in phase (n=6 pts), and the RP2D for tazemetostat was established at 800 mg BID. Baseline characteristics for Arm A N=12, Arm B N=13: 72% males; 96% white, 4% Black; 88% ECOG PS 0-1; 88% had bladder primary, 20% Stage III, 72% stage IV; 80% had visceral or bone metastases. The median number of cycles was 5 in Arm A (range 1-35) and 4 in Arm B (range 2-12). Treatment related G3/4 adverse events (AEs) were observed in 8 patients, most common were anemia and lymphopenia (n=2 each). Treatment related G1/2 AEs included nausea (n=6); skin and subcutaneous tissue disorders (n=3); anemia, lymphopenia, and thrombocytopenia (n=2 each). Among evaluable patients (n=10 in each arm), partial response rate was: Arm A 30%, Arm B 20%; stable disease: Arm A 30%, Arm B 30%; and progressive disease: Arm A 30%, Arm B 20%. 8 pts were on study treatment for ≥ 9 cycles (5 in Arm A, 3 in Arm B). All pts are off protocol treatment. Median progression-free survival was 3.06 (95% CI: 1.38-7.75) months for Arm A and 3.02 (95%CI: 2.4-5.65) for Arm B. Conclusions: Tazemetostat 800 mg BID and pembrolizumab combination is feasible and well-tolerated in patients with advanced UC. In this pilot study, improvement in efficacy relative to historical controls of pembrolizumab alone appears to be modest. Response in tumors with COMPASS-related mutations and EZH2 activity will be evaluated. Clinical trial information: NCT03854474 .

e23270 Background: Melanoma is the most lethal form of skin cancer which have seen drastic improvement in patient survival over the last decade. BRAF is the most common driver mutation in melanoma, seen in ≈50% of all patients (≈30% of patients > 65). The use of BRAF & MEK inhibitors yields high response rates, though it is limited by toxicity and development of acquired resistance. Acknowledging these limitations, we aimed at assessing the efficacy and toxicity of these agents in melanoma patients > 65. Methods: We identified electronic medical records of all melanoma patients > 65 that were treated with BRAF & MEK inhibitors at our institution over the years 2017-2023. Data was retrospectively collected including demographics, disease characteristics, treatment given, response patterns and toxicity. Results: 106 patients were identified. The median age was 71 (65-89), 55% were males. The median follow up was 28.9 months. 32 (30%) patients were treated at first line, 58 (55%) at second line and 16 (15%) at third line. 88 (83%) evaluable patients received treatment for unresectable/metastatic disease of which 84% had an objective response (60% partial response, 24% complete response). Response rate (RR) was 82%, 85% and 87% for first, second and third line respectively. RR was 86% for patients with an increased serum lactate dehydrogenase. 33% of patients had active central nervous system (CNS) metastases at treatment initiation, for whom the systemic RR was 80% and the CNS RR was 39%. The median progression free survival (PFS) was 7.9 months, with a PFS of 6, 8.3 and 13.4 months for first, second and third line respectively. The median PFS was 5.7 months for patients with active CNS disease. The median overall survival (OS) from treatment initiation was 15.7 months (12.5, 14.5, 31.9 for first, second & third line respectively). The median OS for patients with CNS disease was 9.8 months. 16 patients were treated in the adjuvant setting, of which 6 (37%) finished treatment as planned, 3 stopped due to disease progression (19%) and 6 stopped due to toxicity (37%). 88% of patients experienced adverse events (AEs) of any grade, with 27% having grade 3-4 toxicity. There were no grade 5 toxicities reported. 36% of patients experienced one AE, while 52% experienced two or more. 21% of patients stopped treatment due to toxicity, 28% needed a dose reduction and 20% changed to different BRAF/MEK inhibitors. 10% of patients needed systemic corticosteroids to treat AEs. The most common toxicities seen were fever (30%), fatigue (30%), skin rash (22%), elevated liver function tests (20%), arthralgia/myalgia (15%), nausea (14%) and diarrhea (11%). 7% had decrease in cardiac ejection fraction with one grade 3 leading to treatment discontinuation. Conclusions: Treatment with BRAF & MEK inhibitors is challenging in older patients, with a high prevalence of toxicity leading to treatment modifications and discontinuation. Efficacy seems to be the same as in the general population.