Targeted Oncology最新文献

{"title":"MET Alterations in Cancer and MET-Targeted Therapy: Detection Strategies, Treatment Efficacy, and Emerging Technologies.","authors":"Jieun Park, Chaithanya Chelakkot, Ji-Hye Nam, Hun Seok Lee, Chae Rin Kim, Yeonwoo Lee, Mi-Sook Lee, Yoon-La Choi, Young Kee Shin","doi":"10.1007/s11523-025-01166-0","DOIUrl":"https://doi.org/10.1007/s11523-025-01166-0","url":null,"abstract":"<p><p>The MET signaling pathway is dysregulated in several cancers through various mechanisms, including gene mutations, amplifications, rearrangements, and protein overexpression. MET inhibitors have demonstrated clinical benefits in solid tumors including non-small-cell lung cancer (NSCLC), highlighting the importance of optimizing MET alteration detection methods and cut-off values to enhance the efficacy of MET-targeted therapies and improve patient outcomes. Research on MET alterations has primarily focused on MET exon 14 skipping mutations, MET amplification, and MET overexpression. This review summarizes the frequency of MET alterations across different cancer types and the clinical validation of MET alterations in MET-targeted therapies, offering a detailed comparison of objective response rates (ORR) for therapies including crizotinib, capmatinib, tepotinib, savolitinib, telisotuzumab vedotin, telisotuzumab adizutecan, and amivantamab. The review also addresses the challenges in detecting MET exon 14 skipping mutations, such as issues with false positives and negatives, and underscores the need for standardization in MET amplification detection. Trials vary in their cut-offs for MET gene copy number (GCN) and MET/CEP7 ratio and MET expression detection methods, leading to inconsistencies in detection. Additionally, emerging technologies such as circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) analyses have been investigated for their potential to improve MET alterations detection. This review also highlights studies that demonstrate the potential of MET ctDNA and CTC analyses to predict treatment responses and identify resistance mechanisms in MET-targeted therapies.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2-Positive Urothelial Carcinoma: Current Evidence on Targeted Agents and Immunotherapy-Based Combinations.","authors":"Federica Ciciriello, Gaetano Pezzicoli, Antonello Biasi, Claudia D'Addario, Francesco Salonne, Camillo Porta, Mimma Rizzo","doi":"10.1007/s11523-025-01165-1","DOIUrl":"https://doi.org/10.1007/s11523-025-01165-1","url":null,"abstract":"<p><p>Despite the introduction of immunotherapy and antibody-drug conjugates (ADCs), 5-year survival rates for advanced urothelial cancer (UC) remain unsatisfactory. Modest results with conventional systemic treatments have prompted the need for tailored therapies that exploit actionable mutations, such as those involving the human epidermal growth factor receptor (HER)-2 proto-oncogene, which plays a key role in regulating cell growth, differentiation, and survival. HER2-positive UC accounts for 13-25% of all locally advanced/metastatic UC. HER2 overexpression in UC varies widely by tumour stage and is usually a late phenomenon associated with poorer prognosis. Given the crucial biological role of HER2 in UC and the proven activity of anti-HER2 drugs in other solid tumours (e.g. breast and gastric cancer), in this comprehensive review, we analyse clinical trials using HER2-targeting strategies in HER2-positive metastatic UC. Clinical trials of anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors in UC have shown limited efficacy. On the other hand, HER2-targeted ADCs such as trastuzumab deruxtecan and disitamab vedotin have shown encouraging results. However, the most interesting data come from the combination of HER2-targeted ADCs with immunotherapy because of the synergistic action of the two drugs: HER2-directed ADCs, with their cytotoxic effect, lead to the release of cancer antigens, enhancing the anti-tumour immune response, which is boosted by the immune checkpoint inhibitor. Moreover, this combination strategy may also offer some advantages in rewiring the tumour microenvironment, favouring an anti-cancer immune response. ADC and immune checkpoint inhibitor combinations are supported by solid preclinical evidence and are emerging as novel and promising tailored therapeutic approaches for advanced UC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Podcast on Real-World Evidence with Avelumab First-Line Maintenance and Treatment Sequencing in Locally Advanced or Metastatic Urothelial Carcinoma.","authors":"Petros Grivas, Helen H Moon","doi":"10.1007/s11523-025-01162-4","DOIUrl":"10.1007/s11523-025-01162-4","url":null,"abstract":"<p><p>Avelumab first-line maintenance is an approved treatment for cisplatin-eligible or -ineligible patients with advanced urothelial carcinoma (UC) who are progression free following first-line platinum-based chemotherapy, based on the results of the JAVELIN Bladder 100 phase 3 trial. In recent years, an increasing number of real-world studies have examined the effectiveness and safety of avelumab first-line maintenance in heterogeneous populations from different countries, expanding the clinical evidence base. In this podcast, we discuss findings from these real-world studies, which have complemented clinical trials and provided additional insights about overall effectiveness, treatment sequencing involving second-line enfortumab vedotin monotherapy or other options, and healthcare resource utilization. We also briefly discuss the evolving treatment landscape in advanced UC in addition to benefits and limitations of real-world studies in general. Overall, across multiple studies involving more than 3000 patients worldwide, real-world outcomes with avelumab first-line maintenance treatment have been consistent with findings from the JAVELIN Bladder 100 trial, confirming the clinical benefits of this treatment approach for patients with advanced UC who are encountered in day-to-day practice.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Oncology in Rare Endocrine and Neuroendocrine Neoplasms: Experiences and Challenges of the CCCMunich^LMU Molecular Tumor Board.","authors":"Klara Dorman, Christoph J Auernhammer, Christine Spitzweg, Ralf Schmidmaier, Svenja Nölting, Matthias Kroiss, Martin Reincke, Christian Schulz, Martin Angele, Jens Werner, Christine Schmid-Tannwald, Josefine Rauch, Mathias Zacherl, Thomas Knösel, Jörg Kumbrink, Andreas Jung, Frederick Klauschen, Amanda Tufman, Danmei Zhang, Lena Weiss, Stefan Böck, Michael von Bergwelt-Baildon, Volker Heinemann, C Benedikt Westphalen, Kathrin Heinrich","doi":"10.1007/s11523-025-01152-6","DOIUrl":"https://doi.org/10.1007/s11523-025-01152-6","url":null,"abstract":"<p><strong>Background: </strong>Comprehensive genomic profiling (CGP) has become more generally accessible to patients with rare cancer, but data on the results and benefits are limited.</p><p><strong>Objective: </strong>Our objective was to gain a real-world understanding of the molecular landscape and targeted treatment options in neuroendocrine tumors, neuroendocrine carcinomas, adrenocortical carcinomas, pheochromocytomas, and carcinoids.</p><p><strong>Patients and methods: </strong>In this retrospective cohort study, we analyzed CGP results and clinical data from patients with neuroendocrine tumors, neuroendocrine carcinomas, adrenocortical carcinomas, pheochromocytomas, and carcinoids who were discussed in the CCCMunich^LMU Molecular Tumor Board (MTB) between May 2017 and April 2023.</p><p><strong>Results: </strong>In total, 104 patients with endocrine and neuroendocrine neoplasms were discussed in the MTB. CGP was technically successful in 99 patients. The most commonly mutated genes were TP53 (29.3%), RB1 (11.1%), and KRAS (10.1%). The highest overall prevalence of pathogenic alterations was detected in neuroendocrine carcinomas (76.9%) and carcinoids (83.3%), and the lowest prevalence of pathogenic alterations was seen in adrenocortical carcinoma (37.5%). Of the 99 patients with successful CGP, 35 received a treatment recommendation from the MTB based on the CGP results. Of these, ten patients ultimately received the recommended treatment. Of the ten treated patients, four experienced a longer progression-free survival under the targeted treatment than under their previous treatment.</p><p><strong>Conclusions: </strong>One-third of patients with rare endocrine and neuroendocrine neoplasms who underwent CGP had a druggable alteration and received a treatment recommendation from the MTB. However, only 28.6% of these patients were treated accordingly. Our experience highlights the unmet medical need for targeted treatment options in patients with rare cancers.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Outcomes of Pembrolizumab in Advanced Melanoma by Age and Sex: A National Population-Based Study.","authors":"Chin Hang Yiu, Alexander M Menzies, Christine Y Lu","doi":"10.1007/s11523-025-01164-2","DOIUrl":"https://doi.org/10.1007/s11523-025-01164-2","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors are standard treatment for advanced melanoma. Pembrolizumab (programmed cell death-1 inhibitor) monotherapy is recommended as first-line treatment. However, real-world evidence on its efficacy and safety in Australia, a region with the highest melanoma incidence, remains limited.</p><p><strong>Objective: </strong>This study aimed to assess real-world outcomes of pembrolizumab in patients with advanced melanoma in Australia.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using national Pharmaceutical Benefits Scheme and National Death Index data via the Australian Bureau of Statistics DataLab. Patients who initiated pembrolizumab monotherapy for stage III/IV unresectable melanoma (1 January, 2017-30 June, 2022) were included. Kaplan-Meier analyses and multivariate Cox regressions were performed to assess overall survival and time to treatment discontinuation. Immune-related adverse events were inferred from corticosteroid and levothyroxine prescriptions. Subgroup analyses were performed by age (18-64, 65-84, ≥ 85 years) and sex.</p><p><strong>Results: </strong>Among 4127 patients, the median overall survival was 816 days. Mortality was higher in patients aged 65-84 years (adjusted hazards ratio 1.39, 95% confidence interval 1.24-1.56) and ≥85 years (adjusted hazards ratio 1.93, 95% confidence interval 1.69-2.21) versus 18-64 years. Median time to treatment discontinuation was 377 days, with a higher discontinuation rate in female individuals (adjusted hazards ratio 1.19, 95% confidence interval 1.09-1.29). Incident corticosteroid and levothyroxine prescriptions were observed in 19.3 and 7.6% of patients, respectively.</p><p><strong>Conclusions: </strong>Our findings align with clinical trials, demonstrating similar survival outcomes. Younger patients benefited more from pembrolizumab, while female individuals had shorter treatment durations. Further research is required to explore immune checkpoint inhibitor efficacy, safety, and treatment disparities.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Podcast on Integrating Genetic Testing for Homologous Recombination Repair Gene Alterations in Patients with Prostate Cancer in the USA: a Multidisciplinary Approach to Overcoming the Obstacles.","authors":"Brittany M Szymaniak, Alicia K Morgans, Neal D Shore","doi":"10.1007/s11523-025-01159-z","DOIUrl":"10.1007/s11523-025-01159-z","url":null,"abstract":"<p><p>Homologous recombination repair (HRR) gene alterations in prostate cancer predispose patients to more aggressive disease and a poorer prognosis. The presence of these HRR gene alterations may inform patient eligibility for clinical trials and targeted therapies, and importantly, through cascade testing, help identify family members at risk of developing an inherited cancer. This finding highlights the importance of testing for HRR gene alterations in patients with prostate cancer. Despite the potential implications of such testing to patient care, in a cross-sectional retrospective study in the USA, only 37.7% of patients with advanced prostate cancer underwent HRR testing between 2014 and 2022. The aim of this podcast is to identify obstacles to testing for HRR gene alterations that healthcare professionals encounter in day-to-day clinical practice, as well as discuss ways to potentially overcome them. In this multidisciplinary podcast, a genetic counselor, a medical oncologist, and a urologist discuss the importance of testing for HRR gene alterations and, using their different clinical perspectives, explore ways that healthcare professionals can integrate testing results into clinical practice.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discontinuation of Immune Checkpoint Inhibition in Patients with Advanced Unresectable Melanoma Achieving CR, PR, or SD.","authors":"Anna M Czarnecka, Paweł Teterycz, Krzysztof Ostaszewski, Piotr Błoński, Magdalena Zielińska, Łukasz Galus, Robert Dziura, Natasza Kempa-Kamińska, Katarzyna Galwas, Bożena Cybulska-Stopa, Jacek Mackiewicz, Marcin Ziętek, Grażyna Kamińska-Winciorek, Katarzyna Kozak, Piotr Rutkowski","doi":"10.1007/s11523-025-01156-2","DOIUrl":"https://doi.org/10.1007/s11523-025-01156-2","url":null,"abstract":"<p><strong>Background: </strong>The optimal duration of immunotherapy (ITH) remains undefined for patients with metastatic melanoma, and debates on de-escalation strategies are ongoing. Patients in the pivotal KEYNOTE and CheckMate trials who experienced a complete response (CR) on ITH had long-term responses, even after treatment was terminated early because of toxicity or at the physician's discretion.</p><p><strong>Objective: </strong>Our study explores the duration of planned ITH drug holidays-intentional ITH suspension until disease progression off treatment-in patients with unresectable and metastatic melanoma treated for at least 6 months with ITH.</p><p><strong>Patients and methods: </strong>We enrolled 222 patients who received anti-programmed cell death protein-1-based ITH, experienced stable disease, partial response, or complete response during ITH, and had no treatment-limiting toxicities.</p><p><strong>Results: </strong>At a median follow-up of 63 months since the first ITH cycle, median overall survival after the drug holiday start (OS3) was not reached, and the 5-year OS3 rate was 79.3%. Median progression-free survival since the start of drug holiday (PFS3) was not reached, with a 3-year PFS3 rate of 65% for all patients, and the highest rate was in the complete response group (72.3%). After the drug holidays, upon disease progression off treatment, the objective response rate to ITH reintroduction was 58.9%. Again, durable, ongoing objective responses were achieved on ITH reintroduction after drug holidays. The best radiological response achieved before drug holidays correlated with the duration of ITH drug holidays, with the longest duration of disease control without treatment for complete responders.</p><p><strong>Conclusions: </strong>Drug holidays in patients with unresectable and metastatic melanoma after an objective response or prolonged disease stabilization during ITH result in durable control of the disease, particularly in patients with complete response.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship of Prior Anticancer Treatments with Palbociclib Clinical Outcomes in Patients with HR⁺/HER2^- Advanced Breast Cancer in Real-World Settings.","authors":"Gabrielle B Rocque, Joanne L Blum, Yan Ji, Timothy Pluard, John Migas, Shailendra Lakhanpal, Erin Jepsen, Yao Wang, Monica Z Montelongo, Zhe Zhang, Eric Gauthier, Debu Tripathy","doi":"10.1007/s11523-025-01158-0","DOIUrl":"https://doi.org/10.1007/s11523-025-01158-0","url":null,"abstract":"<p><strong>Background: </strong>In the real-world POLARIS study, patients with hormone receptor-positive (HR⁺)/human epidermal growth factor receptor 2-negative (HER2^-) advanced/metastatic breast cancer (ABC) who had received palbociclib + endocrine therapy (ET) had a median real-world progression-free survival (rwPFS) of 20.9 months in the first line of therapy (1LOT) and 13.5 months in second or later LOTs (≥ 2LOT).</p><p><strong>Objective: </strong>The aim of this study is to assess the relationship of prior anticancer treatments with clinical outcomes.</p><p><strong>Patients and methods: </strong>Kaplan-Meier estimates of rwPFS and overall survival (OS) are described by prior anticancer treatments in patients with HR⁺/HER2^- ABC who received palbociclib + ET.</p><p><strong>Results: </strong>A total of 1250 patients received ≥ 1 palbociclib dose (1LOT: 901 [72.1%]; ≥ 2LOT: 349 [27.9%]). In the 1LOT group, 563 (62.5%) had received prior (neo)adjuvant treatments: 24.3% ET alone, 26.6% chemotherapy alone, 45.5% ET + chemotherapy, and 3.6% other treatments; both median rwPFS and OS were numerically longer in patients who had received ET alone (30.4 months and not reached, respectively) and had had no prior treatment (23.7 and 53.3 months, respectively) than in patients with prior chemotherapy alone (15.9 and 38.4 months, respectively). In the ≥ 2LOT group, patients with prior ET alone (21.5%; 19.8 months) or chemotherapy alone (16.6%; 15.5 months) in the (neo)adjuvant and/or metastatic setting had numerically longer median rwPFS than those with prior ET + chemotherapy (41.3%; 11.6 months); OS was comparable regardless of prior treatment.</p><p><strong>Conclusions: </strong>Patients with HR⁺/HER2^- ABC who had received ET alone prior to palbociclib tended to have better clinical outcomes, while those with prior chemotherapy had less clinical benefit.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT03280303.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effectiveness of Atezolizumab Plus Bevacizumab Versus Tremelimumab Plus Durvalumab in Patients with Hepatocellular Carcinoma (HCC) in a Real-World Setting.","authors":"Federica Lo Prinzi, Federico Rossari, Marianna Silletta, Silvia Camera, Silvia Foti, Mara Persano, Francesco Vitiello, Emanuela Di Giacomo, Mariam Grazia Polito, Margherita Rimini, Andrea Casadei-Gardini","doi":"10.1007/s11523-025-01161-5","DOIUrl":"https://doi.org/10.1007/s11523-025-01161-5","url":null,"abstract":"<p><strong>Background: </strong>There are no studies that directly compare atezolizumab plus bevacizumab and tremelimumab plus durvalumab (STRIDE), two first-line options for the systemic therapy of advanced hepatocarcinoma (HCC).</p><p><strong>Objective: </strong>We conducted a real-world retrospective analysis to compare the clinical efficacies of these two regimens.</p><p><strong>Patients and methods: </strong>Using TriNetX data on patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stages B or C, the analysis included patients treated with atezolizumab plus bevacizumab or with the STRIDE regimen. The primary endpoint was overall survival (OS) comparing the two treatment groups.</p><p><strong>Results: </strong>Before applying propensity-score matching, a total of 2,307 consecutive patients were identified. Among them, 1,998 received atezolizumab plus bevacizumab, and 309 were treated with STRIDE. After matching, 618 patients remained, with 309 in each cohort. The analysis showed no significant difference between the two treatments: median OS was 15.4 months (95% confidence interval (CI) 14.7-51.6) and 15.5 months (95% CI 15.0-47.0) for patients treated with atezolizumab plus bevacizumab versus STRIDE, respectively (HR 0.94; 95% CI 0.73-1.22, p = 0.67). The univariate analyses of baseline clinical and laboratory characteristics indicated that the only differentiating factor between the two regimens was better survival for females receiving atezolizumab plus bevacizumab (HR 1.77; 95% CI 1.00-3.16, p = 0.04).</p><p><strong>Conclusions: </strong>Atezolizumab plus bevacizumab and STRIDE demonstrated no statistical difference in OS, showing them to be equally valid alternatives for patients with advanced HCC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dermatologic Adverse Event Mitigation and Management Strategies with Amivantamab + Lazertinib Therapy for Advanced Non-Small Cell Lung Cancer: A Vodcast.","authors":"Danny Nguyen, Edgardo S Santos","doi":"10.1007/s11523-025-01163-3","DOIUrl":"10.1007/s11523-025-01163-3","url":null,"abstract":"<p><p>Targeted therapies have transformed outcomes of patients with advanced non-small cell lung cancer. Amivantamab, a bispecific antibody targeting epidermal growth factor receptor (EGFR) and MET, and lazertinib, a third-generation EGFR tyrosine kinase inhibitor, were approved in 2024 for the first-line treatment of EGFR-mutated (exon 19 deletion/exon 21 L858R substitution) locally advanced or metastatic non-small cell lung cancer. While EGFR-targeted therapies have demonstrated clinical efficacy, they are associated with on-target dermatologic adverse events (AEs). This vodcast aims to educate on strategies to mitigate and manage dermatologic AEs associated with amivantamab + lazertinib. The MARIPOSA study assessed amivantamab + lazertinib versus osimertinib in previously untreated patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer. In the same population, the COCOON study assessed the impact of enhanced versus standard dermatologic management on the incidence of grade ≥ 2 dermatologic AEs. In MARIPOSA, amivantamab + lazertinib significantly improved overall survival (median not reached vs 36.7 months) and progression-free survival (median 23.7 vs 16.6 months) versus osimertinib. The most common EGFR-associated dermatologic AEs were rash and paronychia. To address these AEs, the COCOON study evaluated enhanced dermatologic management strategies (including prophylactic oral and topical antibiotics and moisturizer) versus standard of care dermatologic management, which resulted in a two-fold reduction in grade ≥ 2 dermatologic AEs with COCOON versus standard dermatologic management. We further discuss the COCOON prophylactic regimen together with reactive and expert-recommended dermatologic management approaches. In conclusion, amivantamab + lazertinib is an effective treatment that significantly improves overall survival. While dermatologic AEs are common, effective proactive management strategies, as demonstrated in the COCOON study, can help reduce the incidence and severity of dermatologic AEs. Prioritizing education for healthcare providers and patients will facilitate timely identification and proactive and reactive management of these events, ultimately improving the treatment experience for patients undergoing therapy with amivantamab and lazertinib.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}