tbuckley/cabot-search huggingface dataset:
Transarterial chemoembolization (TACE) combined with donafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): A real-world clinical study.
Authors: Weihong Zhang, Bowen Zhu, Yiyang Tang, Miao Xue, Yanqin Wu, Yue Zhao, Wenzhe Fan
Journal: Journal of Clinical Oncology (2024)

e16145 Background: To evaluate the efficacy and safety of TACE combined with Donafenib, which is as a new tyrosine kinase inhibitors therapy recommended by the China liver cancer staging (CNLC) system for the treatment of unresectable hepatocellular carcinoma (uHCC). Methods: We conducted a single-center, retrospective study on patients diagnosed with uHCC treated by TACE plus Donafenib as the first-line therapy between May 2021 and September 2023 at The First Affiliated Hospital of Sun Yat-sen University. The primary outcomes evaluated in this study were progression-free survival (PFS) and overall survival (OS). Local response, one-year survival rate, safety and tolerability were the secondary outcomes. Results: All of 48 eligible patients by August, 2023, with the median age of 59 years. The clinical characteristics were as follows: BCLC stage A:2 (4.2%), B:16 (33.3%), and C:30 (62.5%); Child-Pugh class A:33 (68.8%) and B:15 (31.2%); ECOG PS 0: 27 (56.2%) and 1: 21 (43.7%). In this study, 10 (20.8%) patients had huge intrahepatic lesions, 15 (31.2%) subjects exhibited extrahepatic metastases at multiple sites, 19 (42.2%) patients presented with portal vein tumor thrombus, and 4 patients were diffuse-type HCC.107 TACE sessions were performed. Three patients had liver transplantation as frequent therapy, and histopathological examination of tissue from these subjects revealed complete necrotic foci. The median PFS was 12.8 months (95% CI: 8.66–NA) , mOS was not reached and the one-year OS rate was 87.5% (95% CI: 77%-97%) in the survival results. The tumor objective response rate was 58.3% with 14.5% complete response and 43.7% partial response based on mRECIST assessment. The disease control rate of the study group was 81.3%. The most common treatment-related adverse events (TRAEs) observed were elevated aspartate aminotransferase (AST) levels (75.0%), increase in bilirubin level (72.9%), elevated alanine aminotransferase (ALT) levels (54.2%), hand-foot syndrome (53.1%), diarrhea (29.1%), rashes (22.9%), hair loss (18.4%) and hypertension (12.5%). Twenty-three (46.9%) patients presented with grade 3 or 4 TRAEs including elevated AST levels (22.4%), elevated ALT levels (16.3%), increase in bilirubin level (4%), diarrhea (4%) and hypertension (2%). No Grade 5 TRAEs were observed. Conclusions: The combination of TACE and Donafenib presented good efficacy and tolerability, which could be potentially used as the first-line treatment of Chinese uHCC patients.
Transarterial chemoembolization combined with donafenib or lenvatinib as first-line treatment for unresectable hepatocellular carcinoma: A single-center real-world retrospective study.
Authors: Huan Liu, Mingsheng Huang
Journal: Journal of Clinical Oncology (2024)

e16137 Background: Combined Transarterial chemoembolization (TACE) with tyrosine kinase inhibitor (TKI) treatment has been proven to be beneficial. This study aimed to retrospectively compare the efficacy and safety of Donafenib (DON)-TACE versus Lenvatinib (LEN)-TACE as first-line treatment for unresectable hepatocellular carcinoma (uHCC). Methods: From May 2020 to May 2023, a retrospective analysis was conducted on the clinical data of 93 patients with previously untreated uHCC who underwent treatment at the department of Interventional Radiology of the Third Affiliated Hospital of Sun Yat-sen University. Among them, 49 were in the DON-TACE group and 44 in the LEN-TACE group. The primary endpoint was progression-free survival (PFS) according to mRECIST, and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety outcome. Results: As of the data cut-off date Aug 26, 2023, the median PFS was 221 days (95% CI 141–366) in the DON-TACE group and 173 days (95% CI 108–215) in the LEN-TACE group (HR = 0.783, 95% CI 0.462–1.325, P = 0.362).ORR and DCR of the DON-TACE group were 55.1% (95% CI 40.23–69.33) and 75.51% (95% CI 61.13–86.66), respectively, while those of the LEN-TACE group were 61.36% (95% CI 45.49–75.64) and 81.82% (95% CI 67.29–91.81). No significant difference was observed either in ORR(P = 0.689) or DCR(P = 0.627) between the two groups. The incidence rates of total adverse events for any grade (85.71% vs 100.00%, P = 0.027) and ≥Grade 3 (22.496% vs 45.45%, P = 0.019) were significantly lower in the DON-TACE group. In addition, the incidence rates of AST increased (27.27% vs 56.82%, P = 0.005), diarrhea (6.12% vs 25.00%, P = 0.011), vomiting (0% vs 40.91%, P &lt; 0.001), proteinuria (0% vs 18.18%, P = 0.011), gastrointestinal hemorrhage (0% vs 13.64%, P = 0.048) and hypertension (2.04% vs 36.36%, P &lt; 0.001) for any grade were also significantly lower in the DON-TACE group. Conclusions: DON-TACE and LEN-TACE showed comparable efficacy as first-line therapies for uHCC patients. DON-TACE demonstrated a lower incidence of severe adverse events.
Effect of triplet regimen (single-agent chemotherapy plus anti-PD-1 antibody and tyrosine kinase inhibitors) on survival compared to chemotherapy in the second-line treatment of advanced biliary tract cancer: A retrospective analysis.
Authors: Zhengang Yuan, Peipei Shang
Journal: Journal of Clinical Oncology (2024)

e16132 Background: TOPAZ-1 and KEYNOTE-966 trials have demonstrated the survival benefit of immune checkpoint inhibitors (ICIs) plus chemotherapy in advanced biliary tract cancer (BTC). Although the ABC‐06 study proved the benefits of FOLFOX in 2nd line therapies, the efficacy is limited. There is no consensus regarding the optimal therapy regimen, and more effective therapeutic options are needed. This retrospective analysis aims to evaluate the efficacy of a triplet regimen compared to standard chemotherapy in 2nd line BTC. Methods: Pts &gt; 18 years, with ECOG PS 0/1, histologically confirmed metastatic BTC and progression on 1 st line Gemcitabine-based therapy were eligible. A triple regimen was referred as Cohort A: tislelizumab and other anti-PD-1 antibody, capecitabine or S-1 plus tyrosine kinase inhibitors (TKIs, lenvatinib or anlotinib). Standard chemotherapy was Cohort B: mFOLFOX or irinotecan plus capecitabine. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), overall response rates (ORR), disease control rate (DCR) and safety. Results: This study retrospectively collected and analyzed treatment and clinical information from 121 pretreated BTC pts from Oct. 2021 to Oct. 2023, with a median age of 60 (range 36-82) years and 48% (58) of the pts were female. Among them, 86 patients received the triple regimen, while 35 patients received standard chemotherapy. Pts’characteristics were well balanced between the two groups in terms of gender, age, ECOG score, primary site, CEA, CA199, or presence of distant metastasis. According to the RECIST1.1 criteria, 1 pt achieved CR and 31 pts had PR in the triple treatment cohort, ORR reached 37.2% (95%CI 27.0-48.3%), which was significantly higher than the 2.8% (95%CI 0.1-14.9%) in the standard chemotherapy cohort (p &lt; 0.0001). Accordingly, the DCR of the two groups were 89.5% (95%CI 81.1-95.1%) and 71.4% (95%CI 53.7-85.4%) respectively. As of Oct 31, 2023, all patients developed progression, and the median PFS in cohort A was 6 months, compared to 2.0 months in cohort B (HR, 0.29, 95%CI 0.16-0.52, p &lt; 0.0001). 64 patients of cohort A and 28 patients of cohort B developed death. The median OS in cohort A was 16.0 months, compared to 6.0 months in cohort B (HR 0.35, 95%CI 0.19~0.64, p &lt; 0.0001). Any grade TRAEs occurred in 54.7% pts of cohort A and 42.9% of cohort B. Most common grade 3 TRAEs were hypohepatia (19.8%), hand-foot syndrome (11.6%), gastrointestinal reaction (1.2%) in cohort A, and hypohepatia (8.6%), hand-foot syndrome (2.9%) in cohort B. Conclusions: The retrospective analysis suggests that the triple regimen as second-line treatment for advanced BTC pts may help improve the efficacy and survival, and is worthy of further prospective exploration.
Second-line systematic strategy options for the progression of lenvatinib plus tislelizumab treating unresectable hepatocellular carcinoma: A retrospective study.
Authors: Huang Xiaozhun, Xu Che, Chuling Wang
Journal: Journal of Clinical Oncology (2024)

e16135 Background: Lenvatinib plus Tislelizumab (LEN+TIS) is a first-line systemic treatment for unresectable hepatocellular carcinoma (uHCC) in the real world, however, most uHCC ultimately fail to respond to first-line therapy due to tumor progression or intolerable adverse effects. The progression-free survival (PFS) of Lenvatinib was approximately 8 months in both REFLECT and LEA-002 studies. Therefore, there were doubts about the second-line therapy after progressive disease (PD) of LEN+TIS, and no studies hade reported the specific switching mode. Methods: This study retrospectively analyzed the clinical data of the first-line treatment of uHCC with LEN+TIS in National Cancer Center/Cancer Hospital &amp; Shenzhen Hospital from April 2019 to December 2023. According to the actual use of drugs, Group A changed Lenvatinib to Regorafenib while Tislelizumab was not changed after PD of LEN+TIS; Group B replaced with Regorafenib plus other immune checkpoint inhibitors (including PD-1, PDL-1) after PD of LEN+TIS. The initial dose of Regorafenib was 80 to 160 mg, which could be adjusted according to patient tolerability, with Regorafenib administered orally once daily for the first 3 weeks, every 4 weeks as a cycle; Tislelizumab given 200mg intravenously every 3 weeks. Both group A and B were subdivided into two subgroups based on whether PFS of LEN+TIS had been more than 8 months. Short- and long-term outcomes were assessed by two independent radiologists according to mRESCIST criteria, all statistical analysis was performed using SPSS version 20. Results: After rigorous screening, a total of 446 samples were recruited in this study, including 208 in group A and 238 in group B. The baseline characteristics were comparable between the two groups, all patients were Child-Pugh grade A, and the median follow-up time was 9.8 months. Group A had higher objective response rates (ORR: 31.2%vs26.9%), PFS (7.6vs6.1months), and median overall survival (mOS: 12.8vs11.2months). Subgroup analysis showed that patients in group A who had first-line PFS shorter than 8 months had a better treatment effect than those with first-line PFS longer than 8 months (ORR: 36.9%vs17.7%; DCR:69.2%vs46.8%;PFS: 8.7vs 5.1months; OS: 14.4vs8.9months; P&lt;0.05); patients in group B who were treated with first-line systemic PFS shorter than 8 months was worse than that with first-line PFS longer than 8 months (ORR:12.2%vs38.6%; DCR:45.3%vs68.9%;PFS:5.6vs6.4months;OS:9.1vs12.6months; P&lt;0.05). No new adverse events were observed, no treatment-related deaths occurred in either group. Conclusions: If the PFS of LEN+TIS was shorter than 8 months, Lenvatinib should be changed to Regorafenib, Tislelizumab could be not changed. And if the PFS of LEN+TIS was longer than 8 months, Lenvatinib and Tislelizumab should be changed at the same time, which seemed to achieve better results.
A Classical Epithelial State Drives Acute Resistance to KRAS Inhibition in Pancreatic Cancer
Authors: Anupriya Singhal, Hannah C. Styers, Jonathan Rub, Zhuxuan Li, Stefan R. Torborg, Jung Yun Kim, Olivera Grbovic-Huezo, Huijin Feng, Zeynep Cagla Tarcan, Hulya Sahin Ozkan, Jill Hallin, Olca Basturk, Rona Yaeger, James G. Christensen, Doron Betel, Yan Yan, Iok In Christine Chio, Elisa de Stanchina, Tuomas Tammela
Journal: Cancer Discovery (2024)

Abstract Intratumoral heterogeneity in pancreatic ductal adenocarcinoma (PDAC) is characterized by a balance between basal and classical epithelial cancer cell states, with basal dominance associating with chemoresistance and a dismal prognosis. Targeting oncogenic KRAS, the primary driver of pancreatic cancer, shows early promise in clinical trials, but efficacy is limited by acquired resistance. Using genetically engineered mouse models and patient-derived xenografts, we find that basal PDAC cells are highly sensitive to KRAS inhibitors. Employing fluorescent and bioluminescent reporter systems, we longitudinally track cell-state dynamics in vivo and reveal a rapid, KRAS inhibitor–induced enrichment of the classical state. Lineage tracing uncovers that these enriched classical PDAC cells are a reservoir for disease relapse. Genetic or chemotherapy-mediated ablation of the classical cell state is synergistic with KRAS inhibition, providing a preclinical proof of concept for this therapeutic strategy. Our findings motivate combining classical state–directed therapies with KRAS inhibitors to deepen responses and counteract resistance in pancreatic cancer. Significance: KRAS inhibitors hold promise in pancreatic cancer, but responses are limited by acquired resistance. We find that a classical epithelial cancer cell state is acutely resistant to KRAS inhibition and serves as a reservoir for disease relapse. Targeting the classical state alongside KRAS inhibition deepens responses, revealing a potent therapeutic strategy. See related commentary by Marasco and Misale, p. 2018
Tumor suppressive role of the antimicrobial lectin REG3A targeting the O-GlcNAc glycosylation pathway
Authors: Nicolas Moniaux, Nicolas Geoffre, Alice Deshayes, Alexandre Dos Santos, Sylvie Job, Claire Lacoste, Tung-Son Nguyen, Marion Darnaud, Mélanie Friedel-Arboleas, Catherine Guettier, Janne Purhonen, Jukka Kallijärvi, Gilles Amouyal, Paul Amouyal, Christian Bréchot, Romain R. Vivès, Marie Annick Buendia, Tarik Issad, Jamila Faivre
Journal: Hepatology (2024)

Antimicrobial proteins of the regenerating family member 3 alpha (REG3A) family provide a first line of protection against infections and transformed cells. Their expression is inducible by inflammation, which makes their role in cancer biology less clear since an immune-inflammatory context may preexist or coexist with cancer, as occurs in HCC. The aim of this study is to clarify the role of REG3A in liver carcinogenesis and to determine whether its carbohydrate-binding functions are involved.
Mechanisms of Response and Tolerance to Active RAS Inhibition in <i>KRAS</i>-Mutant Non–Small Cell Lung Cancer
Authors: Haniel A. Araujo, Ximo Pechuan-Jorge, Teng Zhou, Minh Truong Do, Xin Hu, Frank R. Rojas Alvarez, Maria E. Salvatierra, Heladio P. Ibarguen, Richard Lee, Rashi Raghulan, Harshit Shah, Mariela A. Moreno Ayala, Kevin Chen, Nataliya Tovbis Shifrin, Shuhong Wu, Luisa M. Solis Soto, Marcelo V. Negrao, Don L. Gibbons, David S. Hong, Jack A. Roth, John V. Heymach, Jianjun Zhang, Jingjing Jiang, Mallika Singh, Jacqueline A. M. Smith, Elsa Quintana, Ferdinandos Skoulidis
Journal: Cancer Discovery (2024)

Resistance to inactive state-selective RASG12C inhibitors frequently entails accumulation of RASGTP, rendering effective inhibition of active RAS potentially desirable. Here, we evaluated the antitumor activity of the RAS(ON) multiselective tricomplex inhibitor RMC-7977 and dissected mechanisms of response and tolerance in KRASG12C-mutant non-small cell lung cancer (NSCLC). Broad-spectrum reversible RASGTP inhibition with or without concurrent covalent targeting of active RASG12C yielded superior and differentiated antitumor activity across diverse comutational KRASG12C-mutant NSCLC mouse models of primary or acquired RASG12C(ON) or RASG12C(OFF) inhibitor resistance. Interrogation of time-resolved single-cell transcriptional responses established an in vivo atlas of multimodal acute and chronic RAS pathway inhibition in the NSCLC ecosystem and uncovered a regenerative mucinous transcriptional program that supports long-term tumor cell persistence. In patients with advanced KRASG12C-mutant NSCLC, the presence of mucinous histologic features portended poor response to sotorasib or adagrasib. Our results have potential implications for personalized medicine and the development of rational RAS inhibitor-anchored therapeutic strategies. Significance: Our work reveals robust and durable antitumor activity of the preclinical RAS(ON) multiselective inhibitor RMC-7977 against difficult-to-treat subsets of KRASG12C-mutant NSCLC with primary or acquired RASG12C inhibitor resistance and identifies a conserved mucinous transcriptional state that supports RAS inhibitor tolerance. See related commentary by Marasco and Misale, p. 2018.
Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer
Authors: Julien Dilly, Megan T. Hoffman, Laleh Abbassi, Ziyue Li, Francesca Paradiso, Brendan D. Parent, Connor J. Hennessey, Alexander C. Jordan, Micaela Morgado, Shatavisha Dasgupta, Giselle A. Uribe, Annan Yang, Kevin S. Kapner, Felix P. Hambitzer, Li Qiang, Hanrong Feng, Jacob Geisberg, Junning Wang, Kyle E. Evans, Hengyu Lyu, Aislyn Schalck, Ningping Feng, Anastasia M. Lopez, Christopher A. Bristow, Michael P. Kim, Kimal I. Rajapakshe, Vahid Bahrambeigi, Jennifer A. Roth, Kavita Garg, Paola A. Guerrero, Ben Z. Stanger, Simona Cristea, Scott W. Lowe, Timour Baslan, Eliezer M. Van Allen, Joseph D. Mancias, Emily Chan, Abraham Anderson, Yuliya V. Katlinskaya, Alex K. Shalek, David S. Hong, Shubham Pant, Jill Hallin, Kenna Anderes, Peter Olson, Timothy P. Heffernan, Seema Chugh, James G. Christensen, Anirban Maitra, Brian M. Wolpin, Srivatsan Raghavan, Jonathan A. Nowak, Peter S. Winter, Stephanie K. Dougan, Andrew J. Aguirre
Journal: Cancer Discovery (2024)

KRAS inhibitors demonstrate clinical efficacy in pancreatic ductal adenocarcinoma (PDAC); however, resistance is common. Among patients with KRASG12C-mutant PDAC treated with adagrasib or sotorasib, mutations in PIK3CA and KRAS, and amplifications of KRASG12C, MYC, MET, EGFR, and CDK6 emerged at acquired resistance. In PDAC cell lines and organoid models treated with the KRASG12D inhibitor MRTX1133, epithelial-to-mesenchymal transition and PI3K-AKT-mTOR signaling associate with resistance to therapy. MRTX1133 treatment of the KrasLSL-G12D/+; Trp53LSL-R172H/+; p48-Cre (KPC) mouse model yielded deep tumor regressions, but drug resistance ultimately emerged, accompanied by amplifications of Kras, Yap1, Myc, Cdk6, and Abcb1a/b, and co-evolution of drug-resistant transcriptional programs. Moreover, in KPC and PDX models, mesenchymal and basal-like cell states displayed increased response to KRAS inhibition compared to the classical state. Combination treatment with KRASG12D inhibition and chemotherapy significantly improved tumor control in PDAC mouse models. Collectively, these data elucidate co-evolving resistance mechanisms to KRAS inhibition and support multiple combination therapy strategies. Significance: Acquired resistance may limit the impact of KRAS inhibition in patients with PDAC. Using clinical samples and multiple preclinical models, we define heterogeneous genetic and non-genetic mechanisms of resistance to KRAS inhibition that may guide combination therapy approaches to improve the efficacy and durability of these promising therapies for patients. See related commentary by Marasco and Misale, p. 2018.
ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma
Authors: Simone Benitz, Alec Steep, Malak M. Nasser, Jonathan Preall, Ujjwal Mukund. Mahajan, Holly McQuithey, Ian Loveless, Erick T. Davis, Hui-Ju Wen, Daniel W. Long, Thomas Metzler, Samuel Zwernik, Michaela Louw, Donald Rempinski, Daniel J. Salas-Escabillas, Sydney M. Brender, Linghao Song, Ling Huang, Brian K. Theisen, Zhenyu Zhang, Nina G. Steele, Ivonne Regel, Filip Bednar, Howard C. Crawford
Journal: Cancer Discovery (2024)

Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions, to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor PDX1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in a mouse and human. We identified the receptor tyrosine kinase ROR2 as marker of a gastric metaplasia-like identity in pancreas neoplasms. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition. Significance: We discovered the receptor tyrosine kinase ROR2 as an important regulator of cellular identity in pancreatic precancerous lesions and pancreatic cancer. ROR2 drives an aggressive PDAC phenotype and confers resistance to KRAS inhibitors, suggesting that targeting ROR2 will enhance sensitivity to this new generation of targeted therapies. See related commentary by Marasco and Misale, p. 2018.
Sustained Intraprocedural Cardiac Arrest During BASILICA TAVR
Authors: Morgan R. Casper, Garrett Cohen, Benjamin Stripe
Journal: Journal of the American College of Cardiology (2024)

The bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction (BASILICA) procedure allows patients with severe aortic stenosis and anatomical challenges from aortic leaflet orientation, positioning of coronary ostia, and height of sinuses of Valsalva to undergo TAVR. We present a case of intraprocedural cardiac arrest secondary to iatrogenic left main coronary artery obstruction following a successful BASILICA procedure.
Mature B, T and NK-cell, plasma cell and histiocytic/dendritic cell neoplasms: classification according to the World Health Organization and International Consensus Classification
Authors: Judith A. Ferry, Brian Hill, Eric D. Hsi
Journal: Journal of Hematology & Oncology (2024)

Abstract In 2022, two updated classification systems for lymphoid neoplasms were published by the World Health Organization (WHO Classification of Haematolymphoid Tumours, 5th edition, referred to hereafter as WHO-HAEM5) and the International Consensus Conference (ICC) (Alaggio et al. in Leukemia 36(7):1720–1748, 2022; Campo et al. in Blood 140(11):1229–1253, 2022). Both classifications were conceived by both pathologists and clinicians with expertise in the field. The reasons for this have been reviewed previously (Arber et al. in Virchows Arch 482(1):1–9, 2023; Cree in Leukemia 36(7):1701–1702, 2022, Leukemia 36(11):2750, 2022). Given that both groups were using data-driven processes and consensus and used the revised 4th edition of the WHO Classification of Haematolymphoid Tumours (WHO-HAEM4R) as a starting point, it is not entirely surprising that the resulting classifications are quite similar. However, they are not identical and reflect preferences or approaches for certain unsettled areas as well as preferred terminology. In this review, we will compare nomenclature of the WHO-HAEM5 and ICC classifications, focusing on lymphoid neoplasms and lymphoproliferative disorders (LPDs).
Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma
Authors: Hyery Kim, Hee Mang Yoon, Eun Key Kim, Young Shin Ra, Hyo-Won Kim, Mi-Sun Yum, Min-Jee Kim, Jae Suk Baek, Yu Sub Sung, Sang Min Lee, Hyeong-Seok Lim, Byung Joo Lee, Hyun Taek Lim, Dohyung Kim, Jihee Yoon, Hyunwoo Bae, Soojin Hwang, Yun-Ha Choi, Kyung Ah Kim, In Hee Choi, Seung Won Lee, Su-Jung Park, Beom Hee Lee
Journal: Neuro-Oncology (2024)

The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1 manifestations (eg, neurocognitive function, growth reduction, and café-au-lait spots) are unknown.