tbuckley/cabot-search huggingface dataset:
Neoadjuvant pembrolizumab and lenvatinib in resectable mucosal melanoma: NeoPlus study update.
Authors: Lili Mao, Jie Dai, Xue Bai, Yan Kong, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Bin Lian, Bixia Tang, Xieqiao Yan, Xuan Wang, Siming Li, Li Zhou, Xiaoting Wei, Juan Li, Caili Li, Xiaowen Wu, Jun Guo, Lu Si
Journal: Journal of Clinical Oncology (2024)

9580 Background: Combination therapy of anti-PD1 agent with VEGFR inhibitor is a promising therapeutic approach in unresectable or metastatic mucosal melanoma. We conducted this study evaluating neoadjuvant lenvatinib and pembrolizumab in pts with resectable mucosal melanoma. Methods: This was a single-arm, open-label, single-center, phase 2 study conducted from Sep 2021. Eligible pts were adults (18-75 yr) with histologically confirmed, resectable mucosal melanoma. Pts received lenvatinib 20mg qd and pembrolizumab 200mg q3w for 2 cycles, followed by surgery. Pembrolizumab (200mg q3w) continued post operatively for further 15 cycles. The primary endpoint was complete pathologic response (pCR). Secondary endpoints were Relapse free survival (RFS, time from surgery to any event), Overall survival (OS) and safety. Results: Between Sep 2021 and Apr 2023, 26 pts were enrolled, median age was 57 yrs(range: 49-75), 19 were female. Primary sites included: 11 female genital, 8 ano-rectal, 5 head &amp; neck (1 nasal, 4 oral),2 esophageal. 15 pts (58%) were localized disease,11 (42%) were regional lymphatic disease. BRAF V600, NRAS or KIT mutations were presented in 1, 3 and 2 pts, respectively. 21 pts underwent surgery, 2 pts had a pCR (9.5%), 2 near PCR, 4 pPR, with a pathologic response rate of 38% (8/21,95%CI 18-62%). 5 pts did not proceed with planned surgery for pts preference. As of Dec 2023, 12 of 21 resected pts had relapsed (9/11 in female genital,2/4 in ano-rectal, 1/5 in head &amp; neck). Median follow up time was 19.1 months (95%CI 13.7-24.5). Median RFS was 12.4 months (95%CI 4.0-20.8), no difference was observed among these primary sites (female genital: 6.6 months, ano-rectal: 14.1 months, head &amp; neck: not reached). Median DMFS was not reached. IHC data of the resected tumor showed higher CD8+ T cells density in responders (R: pCR+near PCR+ pPR) than non-responders (NR: pNR) (p = 0.046). Tertiary lymphoid structures were detected in 9 pts. Most common TRAEs were hypertension (13, 50%), proteinuria (12, 46%), LDH increased (9,35%), hypothyroidism (8, 31%). Three pts experienced a dose reduction and 5 experienced a dose interruption due to an AE. No grade 4-5 toxicities were observed. Conclusions: Updated results confirmed that the combination of pembrolizumab plus lenvatinib as neoadjuvant therapy had moderate anti-tumor efficacy in resectable mucosal melanoma. Increased CD8+ T cell infiltration was observed in tumor with pathologic response, supporting further investigation in mucosal melanoma.
Antigen-specific profiling for neoadjuvant anti-PD-1 therapy in melanoma.
Authors: Daniel Yoon, Guanning Wang, Ajeya Nandi, Justin Kim, Aaron Nickie, Stella Park, Mary Carberry, Lydia Giles, Khushboo Patel, Ravi K. Amaravadi, Lynn M. Schuchter, Giorgos Constantine Karakousis, Xiaowei Xu, Tara C. Mitchell, Alexander C. Huang
Journal: Journal of Clinical Oncology (2024)

9576 Background: Anti-PD-1 therapy (aPD-1) has had significant clinical success in extending survivability of melanoma patients. However, two-third of the patients do not achieve long-lasting benefits, and currently, there exists no reliable method for predicting clinical response. We test whether monitoring melanoma-specific CD8 T cells in blood, lymph node, and tumor enables us to gain insights into the mechanism of clinical resistance, and identify potential predictive biomarkers. Methods: We leveraged a phase 2 clinical trial of neoadjuvant PD-1 blockade at University of Pennsylvania where patients with stage III melanoma patients receive a pre-treatment biopsy, treatment with a single dose of the aPD-1 therapy, followed by tumor and lymph node resection 4 weeks later, allowing for access to paired blood and tumor samples. We used a combinatorial tetramer system to track panels of 10 HLA-restricted melanoma and viral-specific CD8 T cell populations simultaneously. Results: Out of 35 patients analyzed, 53% of patients had detectable melanoma-specific CD8 T cells. Notably, these cells exhibited exhausted phenotypes both in blood and tumor, whereas viral-specific T cells displayed features resembling effector and memory CD8 T cells in blood and tumor, respectively. Thus. the presence of tumor antigen emerges as a crucial determinant in shaping the phenotype of melanoma-specific CD8 T cells, above that of the tissue microenvironment. Analysis of resected lymph node samples following PD-1 blockade reveals their supportive role in activating and proliferating anti-tumor T cells. Finally, pathologic responders to PD-1 blockade are characterized by both a higher quantity and a less exhausted phenotype of tumor-specific CD8 T cells. This suggests that assessing both the quantity and quality of these T cells can serve as a predictive indicator to distinguish responders from non-responders. Conclusions: These findings highlight the feasibility of antigen-specific profiling in a clinical trial setting, the importance of melanoma-specific CD8 T cells in checkpoint blockade responses, and their potential use an early on-treatment biomarker of clinical outcomes.
Adjuvant BRAF/MEK versus anti-PD-1 in BRAF-mutant melanoma: Propensity score–matched recurrence-free, distant metastasis-free, and overall survival analysis.
Authors: Manja Bloem, Melissa Melanie de Meza, 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, Alfonsus Johannes Maria van den Eertwegh, Karijn Suijkerbuijk, Michel WJM Wouters
Journal: Journal of Clinical Oncology (2024)

9573 Background: Adjuvant BRAF/MEK inhibitors (BRAF/MEKi) and immunotherapy with anti-PD-1 have become the standard of care for resected high-risk stage III and IV melanoma, but a head-to-head comparison is lacking. In our earlier study, we compared adjuvant BRAF/MEKi and anti-PD-1 in a nationwide cohort in the Netherlands. However, the follow-up was too limited for overall survival (OS) analysis. We present an updated analysis including OS with extended follow-up. Methods: We included all resected high-risk stage III melanoma patients treated with first-line adjuvant BRAF/MEKi and anti-PD-1 from the Dutch Melanoma Treatment Registry from 2018-2023. We performed a propensity score matched outcome analysis of 1- and 2-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and OS. Grade ≥ 3 toxicity rates and discontinuation rates due to toxicity were described. Results: In total, 225 BRAF/MEKi-treated patients and 729 anti-PD-1-treated patients were included. BRAF/MEKi-treated patients had lower disease stages (16.4% versus 10.2% stage IIIA disease; p=0.01) and more comorbidities (76.0% versus 63.8%; p&lt;0.01) than anti-PD-1-treated patients. Median follow-up duration was 20.9 months. Two similar groups of 213 patients each were created by propensity score matching. Before matching, RFS and DMFS were significantly shorter in the anti-PD-1 treated patients, OS was not (Table). After matching, the 1- and 2-year RFS, DMFS and OS rates were not significantly different (Table). Toxicity data will be presented at the meeting. Conclusions: Our results suggest no significant differences in outcomes between adjuvant BRAF/MEKi and anti-PD-1 treatment in stage III melanoma.[Table: see text]
Characterization of driver oncogenic mutations of in-transit melanoma metastases.
Authors: Mohamad El Moheb, Susan Kim, Chunyan Cao, Yunwei Zhang, Mahnoush S Shafiei, Chengli Shen, Kathleen Haden, Lynn T Dengel, Mohammad Fallahi-Sichani, Allan Tsung, Craig Slingluff, Russell G Witt
Journal: Journal of Clinical Oncology (2024)

9586 Background: In-transit melanoma (ITM) is a distinctive form of melanoma metastasis, marked by aggressive locoregional progression and characterized by the entrapment of tumor cells within the lymphatic channels before reaching regional lymph nodes (LN). The mechanisms leading to lymphatic trapping rather than progression to distant metastasis are not well-understood. Previous research indicates a clonal origin for ITM, suggesting specific early-stage genetic alterations may drive this clinical phenotype. In this study, we sought to identify driver oncogenic mutations specific to ITM that may serve as potential targets. Methods: We analyzed data from the MSK-IMPACT database, which includes targeted sequencing of 341-468 genes for patients with cutaneous melanoma. Patients were stratified into four groups based on the type of sample sequenced: in-transit, primary tumor, regional LN, and distant metastases. We examined the prevalence of driver mutations and genetic variants across these groups, adjusting for multiple comparisons. Results: A total of 528 patients were included, of which 74 were in the ITM, 103 in the primary, 133 in the regional LN, and 218 in the metastatic group. The mean age of the cohort was 59 years (SD = 16) and 67% were male. Among the in-transit samples, 68% were treatment-naïve at the time of sequencing, 36% received anti-PD1 monotherapy, and 12% received anti-PD-1 combination therapy. None of the patients received targeted therapy. NRAS Q61 driver mutations were significantly more common in ITM than all other groups (all p&lt;0.05). NF-1 driver mutations were significantly less common in ITM than distant metastasis (p=0.007) (Table). Comparative analysis across all genes showed a lower incidence of NF-1 mutations in ITM relative to metastatic samples (12% vs 38%, p=0.007). Gene interaction analysis showed mutual exclusivity between NRAS and PAK5 mutations in ITM (p=0.02), but not in other groups (p&gt;0.05). Conclusions: This study reveals distinct driver oncogenic mutations specific to ITM, characterized by a high incidence of NRAS mutations, retained NF-1 function and the novel finding of mutual exclusivity between NRAS and PAK5. Closer examination of the interplay between NRAS, NF-1 and PAK5 interactions in ITM may provide deeper insights into the molecular mechanisms of ITM and offer potential therapeutic targets for ITM. [Table: see text]
Length of treatment after partial or complete remission in immunotherapy for metastatic melanoma: An EUMelaReg real world study.
Authors: Nethanel Asher, Peter Mohr, Eva Ellebaek, Marc Bender, Joanna Mangana, Lidija Kandolf, Iva Gavrilova, Paolo Antonio Ascierto, Helen Gogas, Piotr Rutkowski, Dirk Schadendorf, Lars Bastholt, Michael Weichenthal
Journal: Journal of Clinical Oncology (2024)

9531 Background: A significant proportion of patients (pts) with non-resectable melanoma treated with immune checkpoint inhibitors (ICI) achieve durable remissions, but there is limited data on the optimal duration of ICI therapy in these pts. Therefore, the influence of the duration and maintenance of ICI therapy in pts with a partial (PR) or complete remission (CR) on further outcome was investigated. Methods: Primary objectives was the survival outcome after achieving PR or CR in non-resectable stage III/IV melanoma in relation to baseline prognostic variables and duration of maintenance treatment with ICIs in 1 st line. This retrospective study evaluated melanoma cases from the EUMelaReg treatment registry, who achieved a best overall response (BOR) of PR or CR with either single agent anti-PD1 or combined anti-PD1/anti-CTLA4 in 1 st line. Cases were stratified according to treatment duration after achieving a PR or CR: &lt; 6 months (M), 6-12 M, &gt; 12 M. To address immortal time bias, cases with early progression were cloned into all respectively compatible strata. These synthetical strata were further analyzed and compared by propensity score weighting, and robust confidence intervals were retrieved by bootstrapping techniques. Results: A total of 1,291 pts were included in the analysis. After cloning, 2,144 cases could be stratified to the synthetical arms of &lt;6 M (26.5%), 6-12 M (31.4%) or &gt;12 M (42.1%) treatment continuation after achieving PR or CR. Adjusted Kaplan-Meier estimates showed that treatment until progressive disease (PD) or &gt; 12 M after remission resulted in prolonged progression-free (PFS) and overall survival (OS) compared to the &lt; 6 M arm (hazard ratio (HR): 0.82 [95% confidence interval (CI): 0.6-0.9] and HR: 0.67 [95% CI: 0.5-0.9], respectively).This effect was more pronounced in PR (HR 0.66 for OS) than in (HR 0.84 for OS). Treatment for 6-12 M compared to &lt; 6 M also showed a trend towards prolonged PFS and OS (HR: 0.85 [95% CI: 0.7-1.1] and HR: 0.82 [95% CI: 0.6-1.1], respectively). Conclusions: This study showed PFS and OS benefit for pts continuing on treatment for &gt; 12 M or until progression after achieving PR or CR compared to pts treated for &lt; 6 M. [Table: see text]
PD-1 inhibitors versus conventional therapies for adjuvant treatment of resected acral melanoma: A systematic review and meta-analysis.
Authors: Yu Xu, Tong Li, Wei Sun, Wangjun Yan, Chun-Meng Wang, Tu Hu, Xiaowei Zhang, Zhiguo Luo, Xin Liu, Yong Chen
Journal: Journal of Clinical Oncology (2024)

e21555 Background: Acral melanoma (AM) is a rare and aggressive melanoma subtype with unique characteristics in western Caucasian population, but mostly prevalent in Asian population. FDA has approved pembrolizumab and nivolumab for the adjuvant treatment of melanoma. However, its role in AM is still unclear. In US and mainland of China, high-dose interferon alfa was once approved, while in other part of the world, there was no standard treatment for adjuvant therapy of AM. Thus, we performed a meta-analysis to summarize the efficacy of anti-PD-1 monotherapy in patients with AM in adjuvant setting and derive implications for early-stage AM management. Methods: A systematic review of electronic databases was conducted to identify studies that assessed relapse-free survival (RFS) and overall survival (OS) between adjuvant PD-1 and conventional therapy (interferon (IFN) / chemotherapy) or observation alone in patients with AM. RFS was the primary endpoint, OS was the secondary endpoint. We estimated RFS/OS using the fixed-effect model. Statistical analyses in our study were carried out using Stata 12.0 (Stata Corp LP, College Station, TX, USA). Results: Five retrospective studies that totally involving 516 patients with AM were recruited, including 3 China studies and 2 non-China studies. Among them, there were 260 PD-1, 74 IFN, 178 OBS and 4 chemotherapy, respectively. Adjuvant PD-1 inhibitor achieved better efficacy than conventional therapy, showing significant improvement both in RFS (HR 0.76, 95%Cl 0.61-0.95) and OS (HR 0.57 0.37-0.88). This trend of RFS/OS benefit was observed in all subgroups, includes control treatment (OBS/IFN) or study region (China/non-China). Conclusions: Our data supports that patients with resected AM are more likely to derive benefit from adjuvant PD-1 comparing to conventional treatment or observation alone. Perspective studies are warranted to explore the role of adjuvant PD-1 in AM. [Table: see text]
A randomised, controlled, multicentre trial of imiquimod versus radiotherapy for lentigo maligna.
Authors: Angela M Hong, Serigne N Lo, Gerald B Fogarty, Jonathan Stretch, Wei Wang, Pablo Fernandez Penas, Richard CW Martin, Matthew C Foote, Hans Peter Soyer, Jeremy Ruben, Victoria Mar, Lilian Rocha, Christopher Wratten, Helena Collgros, Amanda Regio Pereira, Bruna Melhoranse Gouveia, Richard A Scolyer, Madeleine T King, Pascale Guitera
Journal: Journal of Clinical Oncology (2024)

9502 Background: Lentigo maligna (LM) is a form of melanoma in situ that occurs mainly on sun exposed skin. For patients with LM who are not suitable for surgery due to location, size, patient preference or co-morbidities, topical imiquimod or radiotherapy are alternative non-surgical treatments. There are no prospective randomized controlled trial data to form the basis of any recommendations for the management of LM. This multi-institutional, international randomized phase 3 trial evaluated the efficacy and safety of imiquimod verus radiotherapy for patients with LM. The primary hypothesis was that treatment of LM with topical imiquimod would result in fewer treatment failures than radiotherapy. Methods: Patients aged &gt; 18 years old with LM not suitable for surgery were randomly assigned (1:1) to imiquimod or radiotherapy. The primary endpoint was treatment failure within 24 months. Secondary endpoints included development of invasive disease within the area, side effects and patient-reported quality of life (QOL) assessed with validated questionnaires (skin-specific Skindex-16 and generic EQ-5D-5L). Results: Between August 2015 and November 2021, 126 patients were randomised from 8 centres (imiquimod 60, radiotherapy 58 in final analysis). The median age was 72 years and 94.9% of lesions were on the head and neck area. Median follow-up was 27 months (range 3-62 months). Six (10.5%) patients in the imiquimod group and 12 (24.0%) patients in the radiotherapy group developed recurrence within 24 months (OR 2.68, 95% CI, 0·92-7.8, p = 0.063). Median time to recurrence was not reached in either group. Treatment failure was significantly different within the subgroup of patients who had reflectance confocal microscopy (RCM) follow up of the LM (imiquimod 4/46, 8.7% radiotherapy 13/52 25.0%; OR 3.50 95% CI 1.05-11.65, p = 0.033). Only one RCM feature was associated with failure at 24 months and significantly different between treatment groups : the presence of atypical round cells at the dermal-epidermal junction (6.9 % of imiquimod failure and 27% of radiotherapy failure: p = 0.035). There were no differences between trial groups in patient-reported skin symptoms (itching, burning/stinging, pain, irritation), skin-specific emotional and functional QOL impacts, or generic QOL at any time points. Conclusions: Both imiquimod and radiotherapy are valid, well-tolerated and efficient non-surgical options for LM. There is no significant difference in the acute or long term QoL for the two treatments. Clinical trial information: NCT02394132 .
Case series: Outcomes of immunotherapy in locally advanced and metastatic cutaneous squamous cell carcinoma in Lakes and Waikato region.
Authors: Ahrabie Yogarajah, Alistair Wickham, Prashanth Hari Dass
Journal: Journal of Clinical Oncology (2024)

e21529 Background: Cutaneous squamous cell carcinomas (CSCC) have an incidence of 425 per 100,000 in New Zealand (1). 5% progress to locally advanced or metastatic disease. Immunotherapy is unfunded for this indication despite excellent response and safety profile (2). The objective was to evaluate real world outcomes of patients who managed to access immunotherapy. Methods: Review of referrals to medical oncology in the Lakes &amp;amp; Waikato region between 1 August 2017 to 31 August 2022 with unresectable locally advanced or metastatic CSCC who had immunotherapy. Patients who were not referred to medical oncology, could not afford immunotherapy and/or unsuitable for a clinical trial were excluded from analysis. Results: 13/15 (86.7%) reviewed were male. Mean age was 71. 7 were locally advanced and 8 were metastatic. 14 self-funded pembrolizumab (11 first line, 3 second line). 1 accessed immunotherapy via a trial. 12 (80%) had significant responses; 3 achieved a complete response and 9 achieved a partial response. Median duration of response was not reached, with a median number of 18 cycles delivered. Median follow up was 23.8 months. 9 (60%) remain alive with ongoing response. 6 died on treatment; 3 from non-malignancy and non-treatment related causes. No Grade IV toxicities were observed. Grade III transaminitis was seen in one patient. Grade I-II toxicities seen in 11 (73.3%), including arthralgia (26.7%), fatigue (20%), transaminitis (13.3%), rash (20%), hypothyroidism (6.7%), diarrhoea (6.7%) and dyspnoea (6.7%). Conclusions: Despite an elderly &amp; comorbid cohort, immunotherapy resulted in durable responses and excellent safety profile, highlighting the unmet need for immunotherapy funding in New Zealand. More understanding is required around the different responses to anti-PD1 therapies for the same malignancy type. (1) Pondicherry A, et al. The burden of non-melanoma skin cancers in Auckland, New Zealand. Australas J Dermatol. 2018 Aug; 59(3):210-213 (2) Hughes B, et al. Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicentre, phase II trial. Ann Oncol. 2021;32(10):1276-1285.
Descriptive and content analysis of breast cancer vlogs on YouTube.
Authors: Nina Morena, Elly Htite, Yitzchok Ahisar, Victoria Hayman, Carrie A. Rentschler, Ari N. Meguerditchian
Journal: Journal of Clinical Oncology (2024)

e21016 Background: Vlogs, or “video blogs,” are personally-created experiential videos based on wide-ranging topics, usually posted to YouTube. Many women with breast cancer (BC) document their cancer experiences in YouTube vlogs. These may have the potential to serve as peer-to-peer support and provide community. This study provides a descriptive and content analysis of vlogs by women with BC. Methods: YouTube was searched in incognito mode in 11/2023 using the search terms “breast cancer vlog.” A maximum of 10 videos/creator were included based on viewership and date created. Video characteristics collected included: title, length, number of views, likes, comments, and playlist inclusion. Videos were assessed for sponsorship, presence of explanation and discussion on BC, type of content, and themes. Creator characteristics included age, location, and engagement approaches. Descriptive and content analysis were performed to assess and analyze video content and potential areas where peer-to-peer support may be provided. Results: 90 vlogs by 13 creators were included, all originating from personal accounts. Mean video length, number of views, and number of comments were 21.4 minutes (SD 9.1), 266,780 (SD 534,465), and 1485 (SD 3422), respectively. 38.9% included hashtags. 12.2% included paid sponsorships. Most common filming location was at home (96.7%), followed by the hospital (31.1%), or in the car (21.1%). Home vlogs were most often set in the living room (44.3%), bedroom (33.0%), or kitchen (20.6%). 56.7% included visuals of treatment as well as physical findings. Creators addressed motivation for vlogging in 48.9%; the two most common reasons were wanting to build a community and helping others in a similar situation. In 46.7%, creators explicitly expressed emotion. Most common themes were treatment (85.6%), mental health (81.1%), side effects (72.2%), appearance (63.3%), and family relationships (36.7%). Subthemes included young age, finances, and the importance of online community support. Patient-directed advice was offered in 60.0%, mostly on treatment-related issues. In 56.7%, creators provided explicit treatment definitions. Chemotherapy was discussed in 70.0%; surgery in 57.8%, primarily mastectomy; radiation in 30.0%; general side effects in 71.1%. 24.4% were about a new diagnosis. When mentioned (44.4%), most common creator location was the USA. When mentioned (30.0%), most common age demographic was 20-29 years old. Conclusions: Vlogs by women with BC receive significant levels of engagement. The dedication to building community demonstrated by vlog creators, and the personal nature of their storytelling, advice, and suggestions, may make these vlogs a potential resource for peer-to-peer support.