tbuckley/cabot-search huggingface dataset:
Efficacy of encorafenib/binimetinib in patients with metastatic melanoma with brain metastases: Results from the nationwide Dutch Melanoma Treatment Registry.
Authors: Manja Bloem, Olivier Jules van Not, Maureen J.B. Aarts, Franchette Van Den Berkmortel, Christian U. Blank, Willeke Blokx, Marye J. Boers-Sonderen, Han J. Bonenkamp, Jan Willem de Groot, John Haanen, Geke Hospers, Ellen Kapiteijn, Djura Piersma, Rozemarijn van Rijn, Marion Stevense - den Boer, Astrid Aplonia Maria Van Der Veldt, Gerard Vreugdenhil, Michel WJM Wouters, Karijn Suijkerbuijk, Alfonsus Johannes Maria van den Eertwegh
Journal: Journal of Clinical Oncology (2024)

9528 Background: Data on the effectiveness of encorafenib plus binimetinib in patients with melanoma brain metastases (BMs) are lacking. Therefore, we aimed to investigate the effectiveness of encorafenib/binimetinib treatment in melanoma patients with BMs. Methods: All melanoma patients with BMs treated with encorafenib/binimetinib between 2019 and 2023 in the Netherlands were included from the nationwide Dutch Melanoma Treatment Registry. Patients with prior BRAF/MEK inhibition treatment were excluded. We analyzed overall response rates (ORR), progression-free (PFS), and overall survival (OS) from start of encorafenib/binimetinib. We performed subgroup analysis for symptomatic versus asymptomatic BMs and previous treatment versus no previous treatment. Results: In total, 208 patients were included. Median age was 61 years and 58.2% of the patients was male. Lactate dehydrogenase levels were elevated in 48.1% of the patients and symptomatic BMs were present in 63.5%. Of all patients, 41.8% received prior immunotherapy and for 58.2% encorafenib/binimetinib was the first-line treatment. The median follow-up duration was 23.2 months. The ORR was 67.3%. Median PFS was 5.6 months (95% confidence interval (CI): 4.9-6.2) and median OS was 10.9 months (95% CI: 9.6-14.0). OS was significantly shorter in patients with symptomatic BMs versus asymptomatic BMs (median 9.7 versus 22.9 months, p&lt;0.01), while PFS was similar (median 5.6 versus 5.8 months, p=0.07). Previously untreated patients had worse prognostic characteristics than previously treated patients. PFS was not significantly different between patients with versus without previous systemic treatment (median 8.8 versus 5.2 months, p=0.08), while OS from start of encorafenib/binimetinib was longer for previously treated patients (median 15.9 versus 9.6 months, p&lt;0.01). Conclusions: Encorafenib plus binimetinib has clinical activity in real world melanoma patients with BMs, but PFS and OS are shorter than previously reported for patients without brain metastases. These data may aid physicians in clinical decision-making.
Implementation of hematology oncology lecture series for nursing staff.
Authors: Shirley Eng, Amir S. Steinberg, Joseph Quintas, Sammy Moussly, Richard Sweeney, Juan Trias, Carmel Sauerland, Patricia Kretschmer, Cynthia Wantroba
Journal: Journal of Clinical Oncology (2024)

e21005 Background: Westchester Medical Center has an oncology unit that provides care for hundreds of patients annually. Inpatient cancer patients often have especially complex medical treatment plans that require interdisciplinary collaboration and specialized knowledge of oncologic conditions. There is a need to implement formal teaching tailored to nursing staff devoted to topics in hematology and oncology. Our goal was to develop a monthly lecture series for nursing that deepened their understanding of cancer treatments, enabling them to assess and monitor patients with greater expertise. Methods: Topics were chosen based on relevance and are listed in the table. Speakers included full-time faculty, fellows and residents, pharmacists, and medical students. Ten lectures were completed and scheduled approximately once monthly in the mornings just prior to sign out for nursing shift change. Nursing staff were asked to complete a set of questions prior to each lecture (Pre-Test) They were given the same set of questions after each lecture (Post-Test) to determine whether there was an improvement in understanding of the topic. Informational handouts were distributed at the end of each lecture to provide participants with a summary of key points. A survey administered at the conclusion of the lecture series was collected to assess attitudes towards the lectures. Results: Overall test scores improved after each lecture was given, as demonstrated in the table: Pre and Post Lecture Test Scores. Additionally, feedback regarding the lectures was positive. 100% agreed that they gained a better understanding of topics related to hematology oncology and 92% agreed that participation in these lectures has improved their ability to function collaboratively on interprofessional healthcare teams. Conclusions: A didactic lecture series is a valuable component of hematology oncology education for nursing staff and will improve quality of care of the oncology service. Some limitations of this lecture series concerned nursing staff scheduling conflicts and their availability for lecture attendance. Possible interventions in the future may include setting aside time dedicated for monthly lectures and scheduling lectures for afternoons to avoid conflicts with shift changes and morning rounds. Nevertheless, our findings highlight the value of continued education in empowering nursing staff to deliver quality care to hematology oncology patients.[Table: see text]
Cutaneous melanoma during pregnancy: Management and real-world outcomes.
Authors: Ashley Hickman, Katherine Emilie Rhoades Smith, Corrine K. Nelson, Carl H. Rose, Robert R. McWilliams, Lisa A. Kottschade, Svetomir Markovic, Yiyi Yan, Tina J. Hieken, Matthew Stephen Block
Journal: Journal of Clinical Oncology (2024)

e21554 Background: Pregnancy associated melanoma (PAM) occurs in 1% of female patients with melanoma and affects 1 in 2200 pregnancies. Antepartum evaluation of melanoma must incorporate both maternal and fetal factors, and currently there is lack of standardization. Our study aimed to review the incidence of antepartum melanoma at our institution and highlight patterns in management and treatment during this high-risk scenario. Methods: After IRB approval, the Mayo Clinic electronic medical record was searched with key words “melanoma” and “pregnancy”. 25 patients with melanoma during pregnancy were identified from 1987-2023. 6 patients were excluded as skin changes noted during pregnancy were not formally diagnosed as melanoma until after delivery. Abstracted data included demographic information, disease characteristics, staging (per AJCC guidelines at time of diagnosis), and clinical outcomes. Survival data were calculated. Results: 19 patients were included. Diagnosis occurred at an average maternal age of 30 years (range 24-38 years) and a mean gestational age of 20 weeks (range 6-35 weeks). All patients had a term delivery. 4 patients underwent labor induction at 37 weeks for staging/treatment. 60% of patients had a delay in imaging or treatment attributed to pregnancy, including 1 patient who was upstaged with metastatic disease based on postpartum imaging. 82% of stage I-III patients underwent wide local excision during pregnancy; however, 35% of sentinel lymph node sampling was delayed until postpartum. 3 stage II/III patients received adjuvant therapy (interferon or sargramostim) after delivery. Adjuvant immunotherapy was discussed with 2 patients in the postpartum period but ultimately not given due to the time lapse between surgery and delivery. 1 patient with stage IV disease diagnosed at a gestational age of 20 weeks was evaluated with MRI PET scan then treated with vemurafenib monotherapy during pregnancy. Workup and outcomes were reviewed by stage (Table 1). 7 of 19 patients had subsequent pregnancies, and 1 had recurrence of melanoma during a second pregnancy (stage II followed by stage IV). Due to a low number of censoring events, median progression free survival and overall survival were not reached. Conclusions: Melanoma diagnosed during pregnancy can be safely and effectively staged with sentinel lymph node surgery, MRI imaging (PET-MRI vs standard), and CT imaging with shielding without a need for early induction of labor nor a delay in cancer care. Furthermore, we report a patient with stage IV disease treated with vemurafenib during and immunotherapy after pregnancy, indicating that treating stage IV PAM with systemic therapy is a consideration. [Table: see text]
A phase 2 clinical trial of regorafenib in patients with advanced pretreated melanoma (RegoMel).
Authors: Iris Dirven, Manon Vounckx, Jolien Isabel Kessels, Nathalie Vanlaer, Berlinde von Kemp, Giuseppe Fasolino, Bart Neyns
Journal: Journal of Clinical Oncology (2024)

9518 Background: A majority of advanced melanoma patients (pts) will eventually progress despite treatment with PD-(L)1/CTLA-4/LAG-3 immune checkpoint- and BRAF-/MEK-inhibitors (BRAF-/MEKi; restricted to BRAF V600 -mutant pts). Retrospective case observations indicate activity of regorafenib (REGO) in this setting (1). Methods: This single center, prospective, two-stage, phase 2 clinical trial, investigates REGO 80 mg QD (continuous dosing) in pts with advanced melanoma refractory to standard of care treatment. Objective response rate (ORR, by RECIST v1.1) served as the primary endpoint. The sample size (n=16) was determined according to a Simon’s two-stage minimax statistical design; the trial is considered positive if 3 or more responses are observed. Response assessments are performed every 6 weeks (q6w) during the first 24w, and q12w thereafter. Secondary endpoints are safety, progression free survival (PFS) and overall survival (OS). REGO treatment beyond first progression was permitted if considered to be of potential clinical benefit. Database lock was on Jan 9 th , 2024. Results: From Oct 2022 to Sep 2023, 16 pts were enrolled (9 male, med age 61y; AJCC stage IIIC: 1; IV-M1a: 1; -M1c: 12, -M1d: 2, ECOG PS 0-1: 100%). Oncogenic driver mutations were identified in BRAF V600 : 7-, KIT: 3-, NF1: 3-, NRAS Q61K : 2-, RAF fusion: 1 pt. The ORR was 31% (: 5 partial responses (PR) - 4 confirmed in 3 KIT-,and 1 BRAF V600 -mut pt; and 1 unconfirmed in a BRAF V600 -mut pt). One KIT-mut pt had previously progressed on imatinib. The median duration of response (DoR) was 29.7w (range 12-44). The disease control rate (DCR) was 56%. The median time on REGO monotherapy was 12.3w [95% CI 2.3-22.3], treatment is ongoing in 3 pts. At first progression, 6 BRAF V600 -mut pts continued REGO in association with BRAF-/MEKi, in 5 response evaluable pts there is an ORR of 40% (2 PR with DoR of 24w and 30w) and DCR of 80%. At database lock, 11 pts were alive with a median follow up of 48.4w (range 24-63), 13 pts have progressed on REGO monotherapy (median PFS 11.9w [95% CI 3.5-20.3]; median OS was not reached). There were no grade ≥ 4 treatment related adverse events (TRAE); 56% of pts had at least one grade 3 TRAE, including hypertension (n=3) and maculo-papular rash (n=2). There was one toxicity-related REGO discontinuation. Conclusions: This phase 2 clinical trial on REGO monotherapy in advanced pretreated melanoma patients met its primary endpoint and demonstrated significant anti-tumor activity in KIT-mutant melanoma patients. In BRAF V600 -mutant melanoma, continuation of REGO in combination with BRAF-/MEK-inhibitors demonstrated promising activity in patients who previously progressed on BRAF-/MEK-inhibitors for which further prospective investigation is ongoing. 1. Dirven I. et al. ESMO Meeting 2023. Clinical trial information: NCT05370807 .
Treatment-free survival after immunotherapy discontinuation in advanced melanoma: A systematic review and meta-analysis of real-world studies.
Authors: Ziyao Eric Lu, Muhammad Shahmir Abbasi, Adam Ephraim, Colton Hemphill, Caroline Lapp, Heidi Kuznia, Muhammad Zubair Afzal, Keisuke Shirai
Journal: Journal of Clinical Oncology (2024)

e21523 Background: Immune checkpoint inhibitors (ICIs) have altered the treatment landscape of advanced melanoma with remarkable improvements in progression-free survival (PFS). Durable responses to ICI cessation have been shown in early clinical trials for ICI usage in melanoma, although the optimal duration of immunotherapy remains unclear. Treatment-free survival (TFS) after immunotherapy cessation for patients with complete response (CR), partial response (PR), and stable disease (SD) has been reported in real-world studies and may help to guide discontinuation of ICI therapy. Methods: A systematic search was conducted using PubMed, Embase, and the Cochrane Library to identify real-world studies reporting TFS after immunotherapy in advanced cutaneous melanoma patients with CR, PR, and SD at 12 and 24 months. Discontinuation due to iRAEs were included. Effect sizes were pooled using a random-effects model using the meta and metafor packages in R after logit transformation. Inter-study heterogeneity was quantified using I 2 statistic. Results: Systematic review yielded 34 studies investigating TFS in prospective and retrospective studies. Of these, three retrospective cohort studies reported real-world TFS at 12 and 24 months. Overall, 738 patients with advanced melanoma were included in this meta-analysis, with 384 patients in CR, 278 patients in PR, and 76 patients in SD at time of ICI discontinuation. Mean patient age was 66.4 and 61.9% of patients were male. Pooled 12 and 24-month TFS proportions were higher for patients with CR than PR and for patients with PR than SD. Pooled 24-month TFS was statistically significantly greater in patients with CR compared to SD. I 2 statistics showed considerable heterogeneity between studies ( &gt; 80% in CR and PR subgroups). Conclusions: 12 and 24-month TFS after ICI discontinuation was significant for patients with CR and PR to therapy, suggesting the feasibility of ICI discontinuation in patients after therapy response. Pooled 12-month TFS for patients with SD was 66%, although with decline to 36% at 24 months. Limitations of this meta-analysis include a limited number of included studies. Further research is needed to determine the optimal duration of ICI therapy for patients with advanced melanoma depending on best overall therapy response. [Table: see text]
Ethnic disparities in biomarker testing of patients with metastatic NSCLC in the United States: A real-world analysis.
Authors: Diya Jayram, Shreyas S Bellur, Ahmad Ozair, Shahzaib Ahmad, Mohammad Arfat Ganiyani, Atulya Aman Khosla, Andrea McCracken, Suresh Marada, Charlie Hurmiz, Steven Bowman, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2024)

e20617 Background: National Comprehensive Cancer Network guidelines recommend biomarker testing prior to intervention in metastatic non-small cell lung cancer (mNSCLC). However, biomarker testing remains low, particularly in minorities, especially when targeted therapy against actionable driver mutations improves outcomes and quality of life significantly. We sought to determine testing rates and assess disparities between Hispanic and non-Hispanic Whites. Methods: A retrospective cohort study was conducted in accordance with "strengthening the reporting of observational studies in epidemiology" (STROBE) guidelines. All Hispanic and non-Hispanic White patients across a US oncology-focused hospital consortium (Guardian Research Network) were identified from 01/2018 to 01/2023. Socio-demographic details, clinical profiles, and details related to biomarker testing, treatment, and clinical outcomes were extracted. We also ascertained the area deprivation index (ADI) based on zip code as a surrogate for socio-economic stratification. We grouped patients into validated quintiles of ADI. We extracted testing details of the most common driver mutations – EGFR, ALK, KRASG12C, and PDL1. Data were analyzed using descriptive and inferential statistics. Results: Out of 4898 eligible patients with mNSCLC, 9.89% (n = 484/4898) were Hispanic, and 90.11% (n = 4414/4898) were non-Hispanic Whites. Overall testing rates for EGFR, ALK, KRASG12C and PD-L1 were 36.07% (n = 1767/4898), 33.60% (n = 1646/4898), 3.76% n = 184/4898) and 48.42% (n = 2372/4898). EGFR and ALK testing revealed significant differences showing reduced testing in the non-Hispanic White population (Table 1.) Multivariate logistic regression revealed no significant association between ADI, ethnicity and biomarker testing. Four hundred and eighty-three individuals underwent biomarker testing but did not receive treatment. Forty-three percent (n = 205/483) were alive at the time of data extraction, with 5.18% (n = 25/483) identified as Hispanic. Conclusions: Our analysis reveals that biomarker testing remains low in patients with mNSCLC, showing decreased testing rates of EGFR and ALK in non-Hispanic Whites when compared to Hispanic Whites. Purposeful strategies such as education and testing awareness campaigns are warranted to overcome low testing rates in patients diagnosed with mNSCLC.[Table: see text]
Enhanced dacarbazine efficacy in advanced melanoma patients previously treated with immune checkpoint inhibitors in Korea.
Authors: Soo Jung Lee, Jihyun Na, In Hee Lee, Jeeyeon Lee, Seok-Jong Lee
Journal: Journal of Clinical Oncology (2024)

e21528 Background: Immune checkpoint inhibitors (ICI) have revolutionized advanced malignant melanoma treatment. But the lack of effective options post-ICI failure presents a significant challenge. Despite its modest efficacy, chemotherapy with dacarbazine remains practical choice in metastatic melanoma patients after ICI failure. Researchers suggested an increased efficacy of chemotherapy in melanoma patients previously treated with ICI. In this study, we aimed to assess the efficacy of dacarbazine of patients with or without prior ICI treatment. Methods: 71 patients with histologically confirmed malignant melanoma, who diagnosed and underwent chemotherapy between 2011 and 2023 at the Kyungpook National University Chilgok Hospital (Daegu, Korea) were included in this retrospective study. We included patients who had received either dacarbazine single or CVD(Cisplatin, Vinblastine, Dacarbazine) regimen for an unresectable stage IIIC, IIID or IV acral, cutaneous, mucosal melanoma according to American Joint Committee on Cancer(AJCC) 8th edition. Results: Among a total of 71 individuals, there were 16 patients who had not previously received pembrolizumab treatment (DTI-only group). There were 55 patients in the pembrolizumab (pem-DTI group) experienced group. The median PFS was 2.3 months in the DTI-only group and 3.9 months in the pem-DTI group, reflecting a significant PFS difference of 1.6 months. And the median OS was 6.8 months in the DTI-only group and 19.0 months in the pem-DTI group, demonstrating a statistically significant difference. In the univariate and multivariate analysis for PFS, the use of pembrolizumab was advantageous compared to non-use (HR 0.246, 95% CI 0.106-0.576, p= 0.001). The only favorable condition in the univariate analysis for OS was the use of pembrolizumab compared to non-use (HR 0.198, 95% CI 0.068-0.574, p= 0.003). The mean duration of response for the DTI-only group was 4.64 months, while for the pem-DTI group, it was 8.11 months, indicating that the pem-DTI group exhibited a longer duration. Conclusions: We have demonstrated superior PFS and OS in the group of metastatic melanoma patients who received dacarbazine after prior treatment with pembrolizumab compared to those treated with dacarbazine alone. Dacarbazine may still be a valid option after failure of ICI +/- targeted treatment. Future studies should focus on the immunomodulatory effects of dacarbazine on the tumor microenvironment, which could be harnessed to potentially enhance sensitivity to immune checkpoint-based therapy.
Intracranial outcomes with ipilimumab and nivolumab in melanoma brain metastases following progression on anti-PD-1 therapy.
Authors: Sarah E. Lochrin, Hannah L Kalvin, James William Smithy, Parisa Momtaz, Alexander Noor Shoushtari, Katherine Panageas, Michael A. Postow
Journal: Journal of Clinical Oncology (2024)

9555 Background: Ipilimumab + nivolumab (ipi/nivo) is effective for melanoma brain metastases (MBM), but the efficacy of ipi/nivo in MBM in patients (pts) whose melanoma has progressed on anti-PD-1 is unknown. Methods: We conducted a retrospective analysis of pts with progressive MBM who received ipi/nivo at Memorial Sloan Kettering Cancer Center following prior anti-PD-1. Cohort A included pts with ≥1 untreated MBM (≥5mm) without local interventions (such as neurosurgery, radiotherapy). Cohort B included pts who had received local interventions for all MBMs before starting ipi/nivo. The primary endpoint was intracranial (IC) progression free survival (PFS). IC response was assessed based on clinical radiological interpretation for Cohort A. Kaplan-Meier methods were used to estimate time-to-event outcomes. Results: Fifty-seven pts were identified: 28 and 29 in Cohort A and B, respectively. All pts had received prior anti-PD-1, 42% prior ipi, a median of 2 (IQR: 1, 3) prior lines, and 21% (12/57) of pts prior treatment was in the adjuvant setting only. 79% (45/57) of pts had cutaneous, 14% (8/57) acral, 5% (3/57) unknown primary and 2% (1/57) mucosal melanoma. Median age was 64 (IQR: 58, 71) and 55 (IQR: 47, 70) years in Cohort A and B, respectively. Cohort A had median lesion size (largest measurable MBM) of 1.0cm (IQR: 0.60, 2.12), and 64% (18/28) of pts had &gt;5 lesions; Cohort B had a median lesion size 1.5cm (IQR: 1.10, 2.00) and 28% (8/29) of pts had &gt;5 lesions. 14% (8/57) of pts received concurrent steroid (equivalent of ≥dexamethasone 4mg daily) upon starting ipi/nivo, and leptomeningeal disease was present in 14% (4/28) and 7% (2/29) of Cohort A and B, respectively. The IC response rate was 11% (3/28, 2 were complete (CR)) in Cohort A.Both patients with CR were asymptomatic with ≤ 2 lesions and no prior CTLA-4 exposure. Most (20/28, 71%) in Cohort A had best response of progressive disease (PD); all that had a best response of stable disease (SD; 5/28, 18%) sustained that response for less than 6 months. Median IC-PFS was 1.7 (95% CI: 1.3,4.4) and 7.6 (95% CI: 3.6, -) months, and median overall survival (OS) was 6.7 (95% CI: 3.6,10) and 24 (95% CI: 11, -) months in Cohort A and B. 24-month OS was 19% (95% CI: 8.1,45) and 51% (95% CI: 35,75) in Cohort A and B. 30% (8/27) and 66% (19/29) of pts had subsequent systemic therapy, and 48% (13/27) and 52% (15/29) subsequent local therapy in Cohorts A and B. Conclusions: Ipi/nivo has limited efficacy in patients with progressive MBM post-PD-1 therapy in the absence of local therapy. These results highlight the unmet clinical need for more effective therapies to address progressive MBM post-PD-1 therapy, an increasingly relevant clinical scenario particularly in light of the growing use of adjuvant and neoadjuvant anti-PD-1.