Targeted Oncology最新文献

{"title":"Rechallenge with Anti-EGFR Treatment in RAS/BRAF wt Metastatic Colorectal Cancer (mCRC) in Real Clinical Practice: Experience of the GITuD Group.","authors":"Mercedes Salgado Fernández, Margarita Reboredo López, Marta Covela Rúa, Sonia Candamio, Paula González-Villarroel, Luis Felipe Sánchez-Cousido, Begoña Graña, Alberto Carral-Maseda, Soledad Cameselle-García, Vanesa Varela Pose, Maria Elena Gallardo-Martín, Nieves Martínez-Lago","doi":"10.1007/s11523-024-01062-z","DOIUrl":"10.1007/s11523-024-01062-z","url":null,"abstract":"<p><strong>Background: </strong>There are few third- and fourth-line therapeutic options for metastatic colorectal cancer (mCRC). In RAS/BRAF wild-type (wt) mCRC previously treated with anti-epidermal growth factor receptor (anti-EGFR) (first-line) and relapsed after a good response, retreatment with anti-EGFR (rechallenge) emerges as a therapeutic alternative.</p><p><strong>Objective: </strong>The aim was to show the activity and safety of anti-EGFR rechallenge in RAS/BRAF wt mCRC in real-world practice.</p><p><strong>Patients and methods: </strong>A multicenter, retrospective, observational study (six hospitals of the Galician Group of Research in Digestive Tumors) was conducted. Adult patients with RAS/BRAF wt mCRC, evaluated by liquid biopsy, were included. They received anti-EGFR rechallenge (cetuximab, panitumumab) as monotherapy, or combined with chemotherapy, in third- or subsequent lines. Efficacy (overall response rate [ORR], disease control rate [DCR], overall survival [OS], and progression-free survival [PFS]) and safety (incidence of adverse events [AEs]) were assessed.</p><p><strong>Results: </strong>Thirty-one patients were analyzed. Rechallenge (median 6 cycles [range 1-27], mainly cetuximab [80.7%]), started at a median anti-EGFR-free time of 18.4 months (1.7-37.5 months) after two (38.7%) or more (61.3%) lines of treatment; 64.5% of patients received a full dose. Median OS and PFS were 9.8 months (95% confidence interval [CI] 8.2-11.4) and 2.6 months (95% CI 1.7-3.4), respectively. ORR was 10%, and DCR was 30%. The most common AEs were diarrhea (35.5%), anemia (29%), emesis (6.4%), and neutropenia (6.4%); < 5% grade ≥ 3; 48.4% of patients reported anti-EGFR-related skin toxicity (grade > 1). Hypomagnesemia required supplements in 29% of patients. Dose delays (≥ 3 days) and reduction (≥ 20%) were reported in 11 (35.5%) and seven patients (22.6%), respectively.</p><p><strong>Conclusions: </strong>In RAS/BRAF wt mCRC patients, an anti-EGFR rechallenge provides a feasible therapeutic option with clinical benefit (survival) and a manageable safety profile.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"565-573"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082522","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":"Adverse Event Profile of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non-small Cell Lung Cancer: An Updated Meta-analysis.","authors":"Susu Zhou, Noriko Kishi, Parissa Alerasool, Nicholas C Rohs","doi":"10.1007/s11523-024-01073-w","DOIUrl":"10.1007/s11523-024-01073-w","url":null,"abstract":"<p><strong>Background: </strong>Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remain the frontline standard of care for patients with EGFR-mutant non-small cell lung cancer. An updated toxicity profile of EGFR-TKIs proves valuable in guiding clinical decision making.</p><p><strong>Objective: </strong>This study comprehensively assessed the risk of EGFR-TKI-related adverse events (AEs) involving different systems/organs.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, Web of Science, and Cochrane library for phase III randomized controlled trials comparing EGFR-TKI monotherapy with placebo or chemotherapy in patients with non-small cell lung cancer. The odds ratio (OR) of all-grade and high-grade adverse events (AEs) including dermatologic, gastrointestinal, hematologic, hepatic, and respiratory events was pooled for a meta-analysis. Subgroup analyses based on the control arm (placebo or chemotherapy) and individual EGFR-TKIs (erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib) were conducted.</p><p><strong>Results: </strong>Thirty-four randomized controlled trials comprising 15,887 patients were included. The pooled OR showed EGFR-TKIs were associated with a significantly increased risk of all-grade dermatologic AEs including paronychia, pruritus, rash, skin exfoliation, and skin fissures, gastrointestinal AEs including abdominal pain, diarrhea, dyspepsia, mouth ulceration, and stomatitis, hepatic AEs including elevated alanine aminotransferase and aspartate aminotransferase, and respiratory AEs including epistaxis, interstitial lung disease and rhinorrhea. Furthermore, a significantly increased risk of high-grade rash (OR 7.83, 95% confidence interval [CI] 5.11, 12.00), diarrhea (OR 2.10, 95% CI 1.44, 3.05), elevated alanine aminotransferase (OR 3.93, 95% CI 1.71, 9.03), elevated aspartate aminotransferase (OR 3.22, 95% CI 1.05, 9.92) and interstitial lung disease (OR 2.35, 95% CI 1.38, 4.01) was observed in patients receiving EGFR-TKIs. When stratified by individual EGFR-TKIs, gefitinib showed a significant association with all-grade and high-grade hepatotoxicity and interstitial lung disease.</p><p><strong>Conclusions: </strong>Epidermal growth factor receptor tyrosine kinase inhibitors were associated with a significantly increased risk of various types of AEs. Clinicians should be vigilant about the risks of these EGFR-TKI-related AEs, particularly for severe hepatotoxicity and interstitial lung disease, to facilitate early detection and proper management.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"547-564"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186977","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":"Anti-Angiogenic Tyrosine Kinase Inhibitor-Related Toxicities Among Cancer Patients: A Systematic Review and Meta-Analysis.","authors":"Tai Van Nguyen, Diaddin Hamdan, Géraldine Falgarone, Kien Hung Do, Quang Van Le, Frédéric Pamoukdjian, Guilhem Bousquet","doi":"10.1007/s11523-024-01067-8","DOIUrl":"10.1007/s11523-024-01067-8","url":null,"abstract":"<p><strong>Background: </strong>Targeting of angiogenesis has become a major therapeutic approach for the treatment of various advanced cancers. There are many unresolved questions on the toxicity of anti-angiogenic tyrosine kinase inhibitors (TKIs).</p><p><strong>Objective: </strong>We performed a meta-analysis to assess the toxicity prevalence of the different anti-angiogenic TKIs among cancer patients and in subpopulations of interest including patients with renal cell carcinoma.</p><p><strong>Patients and methods: </strong>We searched the MEDLINE and Cochrane Library databases to November 2023. Clinical trials were eligible if they set out to report the grade ≥3 toxicities related to one of the seven currently approved anti-angiogenic TKIs as monotherapies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was applied with PROSPERO (CRD42023411946).</p><p><strong>Results: </strong>The 421 eligible studies included a total of 56,895 cancer patients treated with anti-angiogenic TKI monotherapy. Twenty-four different cancer types were identified, mainly renal cell carcinoma (41.9% of the patients). The anti-angiogenic TKI was sorafenib (34.5% of the patients), sunitinib (30.5%), regorafenib (10.7%), pazopanib (9.4%), cabozantinib (7.7%), axitinib (4.3%), and lenvatinib (2.9%). The pooled prevalence of grade 3 and 4 toxicities was 56.1% (95% confidence interval 53.5-58.6), with marked between-study heterogeneity (I² = 96.8%). Toxicity profiles varied considerably depending on the type of TKI, the cancer type, and the specific patient characteristics. In particular, Asian patients and elderly people had higher prevalences of severe toxicities, with pazopanib being the best-tolerated drug. For patients treated with sunitinib, particularly those with metastatic RCC, there was no significant difference in terms of toxicity according to the regimen schedule.</p><p><strong>Conclusions: </strong>This meta-analysis highlights the toxicity profiles of anti-angiogenic TKI monotherapies, and thus enables high-level recommendations for the choice of anti-angiogenic TKIs on the basis of the patient's age, ethnicity, comorbidities, and comedications, for personalized treatment.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"533-545"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959470","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":"Targeted Alpha Therapy for Glioblastoma: Review on In Vitro, In Vivo and Clinical Trials.","authors":"Maram El Sabri, Leyla Moghaddasi, Puthenparampil Wilson, Frank Saran, Eva Bezak","doi":"10.1007/s11523-024-01071-y","DOIUrl":"10.1007/s11523-024-01071-y","url":null,"abstract":"<p><p>Glioblastoma (GB), a prevalent and highly malignant primary brain tumour with a very high mortality rate due to its resistance to conventional therapies and invasive nature, resulting in 5-year survival rates of only 4-17%. Despite recent advancements in cancer management, the survival rates for GB patients have not significantly improved over the last 10-20 years. Consequently, there exists a critical unmet need for innovative therapies. One promising approach for GB is Targeted Alpha Therapy (TAT), which aims to selectively deliver potentially therapeutic radiation doses to malignant cells and the tumour microenvironment while minimising radiation exposure to surrounding normal tissue with or without conventional external beam radiation. This approach has shown promise in both pre-clinical and clinical settings. A review was conducted following PRISMA 2020 guidelines across Medline, SCOPUS, and Embase, identifying 34 relevant studies out of 526 initially found. In pre-clinical studies, TAT demonstrated high binding specificity to targeted GB cells, with affinity rates between 60.0% and 84.2%, and minimal binding to non-targeted cells (4.0-5.6%). This specificity significantly enhanced cytotoxic effects and improved biodistribution when delivered intratumorally. Mice treated with TAT showed markedly higher median survival rates compared to control groups. In clinical trials, TAT applied to recurrent GB (rGB) displayed varying success rates in extending overall survival (OS) and progression-free survival. Particularly effective when integrated into treatment regimens for both newly diagnosed and recurrent cases, TAT increased the median OS by 16.1% in newly diagnosed GB and by 36.4% in rGB, compared to current standard therapies. Furthermore, it was generally well tolerated with minimal adverse effects. These findings underscore the potential of TAT as a viable therapeutic option in the management of GB.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"511-531"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Podcast on Platinum Eligibility and Treatment Sequencing in Platinum-Eligible Patients with Locally Advanced or Metastatic Urothelial Carcinoma.","authors":"Shilpa Gupta, Helen H-S Moon, Srikala S Sridhar","doi":"10.1007/s11523-024-01074-9","DOIUrl":"10.1007/s11523-024-01074-9","url":null,"abstract":"<p><p>The treatment landscape for patients with advanced urothelial carcinoma continues to evolve. Enfortumab vedotin plus pembrolizumab has received Food and Drug Administration approval based on recent phase 3 trial data showing superior efficacy compared with first-line platinum-based chemotherapy; however, its distinct toxicity profile may make it less suitable for some patients, and availability in some countries may be limited by cost considerations. Consequently, platinum-based chemotherapy is expected to remain an important first-line treatment option. Choice of platinum regimen (cisplatin- or carboplatin-based) is informed by assessment of clinical characteristics, including performance status, kidney function, and presence of peripheral neuropathy or heart failure. For patients without disease progression after completing platinum-based chemotherapy, avelumab first-line maintenance treatment is recommended by international guidelines. For patients who have disease progression, pembrolizumab is the preferred approach. Additionally, following results from a recent phase 3 trial, nivolumab plus cisplatin-based chemotherapy has also received Food and Drug Administration approval and is an additional first-line treatment option for cisplatin-eligible patients. Later-line options for patients with advanced urothelial carcinoma, depending on prior treatment, may include enfortumab vedotin, erdafitinib (for patients with FGFR2/3 mutations or fusions/rearrangements), sacituzumab govitecan, and platinum rechallenge. For the small proportion of patients ineligible for any platinum-based chemotherapy (i.e., unsuitable for cisplatin or carboplatin), immune checkpoint inhibitor monotherapy with pembrolizumab or atezolizumab is a first-line treatment option, although approved agents vary between countries. In summary, this podcast discusses recent developments in the treatment landscape for advanced urothelial carcinoma, eligibility for platinum-based chemotherapy, potential first-line treatment options, and treatment sequencing. Supplementary file1 (MP4 246907 KB).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"483-494"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durvalumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in Biliary Tract Cancer: a Real-World Retrospective, Multicenter Study","authors":"Margherita Rimini, Gianluca Masi, Sara Lonardi, Federico Nichetti, Tiziana Pressiani, Daniele Lavacchi, Lucchetti Jessica, Guido Giordano, Mario Scartozzi, Emiliano Tamburini, Alessandro Pastorino, Ilario Giovanni Rapposelli, Bruno Daniele, Erika Martinelli, Ingrid Garajova, Giuseppe Aprile, Marta Schirripa, Vincenzo Formica, Francesca Salani, Costanza Winchler, Francesca Bergamo, Rita Balsano, Eleonora Gusmaroli, Angotti Lorenzo, Matteo Landriscina, Andrea Pretta, Ilaria Toma, Chiara Pirrone, Anna Diana, Francesco Leone, Oronzo Brunetti, Giovanni Brandi, Silvio Ken Garattini, Maria Antonietta Satolli, Federico Rossari, Lorenzo Fornaro, Monica Niger, Valentina Zanuso, Antonio De Rosa, Francesca Ratti, Luca Aldrighetti, Filippo De Braud, Silvia Foti, Mario Domenico Rizzato, Caterina Vivaldi, Cascinu Stefano, Lorenza Rimassa, Lorenzo Antonuzzo, Andrea Casadei-Gardini","doi":"10.1007/s11523-024-01060-1","DOIUrl":"https://doi.org/10.1007/s11523-024-01060-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed cell death ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC).</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The present study investigated for the first time the impact on survival of adding durvalumab to cisplatin/gemcitabine compared with cisplatin/gemcitabine in a real-world setting.</p><h3 data-test=\"abstract-sub-heading\">Patients and Methods</h3><p>The analyzed population included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab in combination with cisplatin/gemcitabine or with cisplatin/gemcitabine alone. The impact of adding durvalumab to chemotherapy in terms of overall survival (OS) and progression free survival (PFS) was investigated with univariate and multivariate analysis.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Overall, 563 patients were included in the analysis: 213 received cisplatin/gemcitabine alone, 350 received cisplatin/gemcitabine plus durvalumab. At the univariate analysis, the addition of durvalumab was found to have an impact on survival, with a median OS of 14.8 months versus 11.2 months [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.50–0.80, <i>p</i> = 0.0002] in patients who received cisplatin/gemcitabine plus durvalumab compared to those who received cisplatin/gemcitabine alone. At the univariate analysis for PFS, the addition of durvalumab to cisplatin/gemcitabine demonstrated a survival impact, with a median PFS of 8.3 months and 6.0 months (HR 0.57, 95% CI 0.47–0.70, <i>p</i> &lt; 0.0001) in patients who received cisplatin/gemcitabine plus durvalumab and cisplatin/gemcitabine alone, respectively. The multivariate analysis confirmed that adding durvalumab to cisplatin/gemcitabine is an independent prognostic factor for OS and PFS, with patients &gt; 70 years old and those affected by locally advanced disease experiencing the highest survival benefit. Finally, an exploratory analysis of prognostic factors was performed in the cohort of patients who received durvalumab: neutrophil–lymphocyte ratio (NLR) and disease stage were to be independent prognostic factors in terms of OS. The interaction test highlighted NLR ≤ 3, Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0, and locally advanced disease as positive predictive factors for OS on cisplatin/gemcitabine plus durvalumab.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In line with the results of the TOPAZ-1 trial, adding durvalumab to cisplatin/gemcitabine has been confirmed to confer a survival benefit in terms of OS and PFS in a real-world setting of patients with advanced BTC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":"125 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834792","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":"Correction to: Tremelimumab: A Review in Advanced or Unresectable Hepatocellular Carcinoma.","authors":"Nicole L France, Hannah A Blair","doi":"10.1007/s11523-024-01053-0","DOIUrl":"10.1007/s11523-024-01053-0","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"481"},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Futibatinib: A Review in Locally Advanced and Metastatic Cholangiocarcinoma.","authors":"Sheridan M Hoy","doi":"10.1007/s11523-024-01059-8","DOIUrl":"10.1007/s11523-024-01059-8","url":null,"abstract":"<p><p>Futibatinib (LYTGOBI^®) is an oral small molecule compound that selectively, irreversibly and potently inhibits the tyrosine kinase activity of fibroblast growth factor receptor (FGFR)1-4. It is approved in the EU, Japan and the USA for the treatment of adults with locally advanced or metastatic cholangiocarcinoma (CCA) harbouring an FGFR2 fusion or rearrangement who have progressed following systemic therapy. In the phase II part (FOENIX-CCA2) of a multinational phase I/II study in this patient population, monotherapy with futibatinib 20 mg once daily was associated with clinically meaningful and durable responses, sustained health-related quality of life (HR-QOL), and a manageable safety profile with supportive care and as-needed dose modifications. Indeed, hyperphosphataemia (the most common all grade and grade 3 treatment-related adverse event) was manageable with phosphate-lowering therapy and dose reductions or interruptions. Although further efficacy and tolerability data are expected, current evidence indicates that futibatinib is a valuable targeted therapy option for adults with locally advanced or metastatic CCA harbouring an FGFR2 fusion or rearrangement who have progressed following systemic therapy, a patient population with limited treatment options and poor life expectancy.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"473-480"},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899206","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":"Divarasib in the Evolving Landscape of KRAS G12C Inhibitors for NSCLC.","authors":"Danielle Brazel, Misako Nagasaka","doi":"10.1007/s11523-024-01055-y","DOIUrl":"10.1007/s11523-024-01055-y","url":null,"abstract":"<p><p>Kristen Rat Sarcoma viral oncogene (KRAS) mutations are one of the most common oncogenic drivers found in 12-14% of non-small cell lung cancer (NSCLC) and 4% of colorectal cancer tumors. Although previously difficult to target, sotorasib and adagrasib are now approved for previously treated NSCLC patients with KRAS G12C mutations. In preclinical studies, divarasib was 5 to 20 times as potent and up to 50 times as selective as sotorasib and adagrasib. While sotorasib met its primary endpoint in the phase III second line study against docetaxel, the progression-free survival (PFS) benefit was small and no overall survival (OS) benefit was observed. Adagrasib has demonstrated clinical benefit in the phase I/II KRYSTAL-1 study setting, however, 44.8% of patients reported grade 3 or higher toxicities. Divarasib has been studied in a phase I dose expansion cohort with promising efficacy [objective response (ORR) 53.4% and PFS 13.1 months]. Although most patients reported toxicities, the majority were low-grade and manageable with supportive care. Here we discuss these results in the context of the evolving KRAS G12C landscape.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"297-301"},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Evidence of FOLFIRI Combined with Anti-Angiogenesis Inhibitors or Anti-EGFR Antibodies for Patients with Early Recurrence Colorectal Cancer After Adjuvant FOLFOX/CAPOX Therapy: A Japanese Claims Database Study","authors":"Yoshinori Kagawa, Chaochen Wang, Yongzhe Piao, Long Jin, Yoshinori Tanizawa, Zhihong Cai, Yu Sunakawa","doi":"10.1007/s11523-024-01063-y","DOIUrl":"https://doi.org/10.1007/s11523-024-01063-y","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Background&lt;/h3&gt;&lt;p&gt;Oxaliplatin-containing adjuvant regimens (folinic acid, fluorouracil, and oxaliplatin/capecitabine and oxaliplatin [FOLFOX/CAPOX]) are used after curative resection of colorectal cancer (CRC). However, real-world evidence regarding treatment sequences and outcomes in patients with early recurrence CRC after adjuvant chemotherapy is limited.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Objective&lt;/h3&gt;&lt;p&gt;We aimed to describe the patient characteristics, treatment sequence, and overall duration of second-line (2L) therapy in patients with early recurrence CRC who received adjuvant chemotherapy (FOLFOX/CAPOX) followed by folinic acid, fluorouracil, and irinotecan (FOLFIRI) + anti-angiogenesis drugs (AA) or FOLFIRI + anti-epidermal growth factor receptor (EGFR) antibodies.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Methods&lt;/h3&gt;&lt;p&gt;This retrospective study analyzed Japanese administrative data from November 2014 to March 2023 of adult patients who underwent CRC resection surgery, started FOLFOX/CAPOX ≤3 months (mo) after surgery, and had early CRC recurrence. Early recurrence was defined as initiation of FOLFIRI+AA or FOLFIRI+anti-EGFR antibodies as 2L therapy, ≤12 mo of discontinuing adjuvant chemotherapy. Patient characteristics, treatment sequence, median time to treatment discontinuation (mTTD), i.e., duration between the start and end dates of 2L therapy (Kaplan–Meier method), and factors associated with 2L time to treatment discontinuation constituted the study outcomes (Cox regression model). Subgroup analyses were performed for timing of early CRC recurrence (≤6 mo and 6–12 mo) and tumor sidedness.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;Among the 832 selected patients (median age [minimum–maximum] 67 (24–86) years, 56.4% male), CAPOX (71.3%) was more commonly used than FOLFOX (28.7%) as adjuvant therapy. FOLFIRI+AA (72.5%) was used more commonly than FOLFIRI+anti-EGFR antibodies (27.5%) in 2L. AA and anti-EGFR antibodies groups had similar mTTD: 6.2 mo (95% confidence interval 5.8, 6.9) and 6.1 mo (95% confidence interval 5.2, 7.4). Age ≥70 years showed significant association with shorter 2L treatment duration (hazard ratio 1.2, 95% confidence interval 1.0, 1.4; &lt;i&gt;p&lt;/i&gt; = 0.03). The AA cohort’s mTTD was numerically shorter in the ≤6 mo recurrence subgroup compared with the 6–12 mo recurrence subgroup (6.1 mo vs 8.1 mo); the anti-EGFR antibodies cohort had similar mTTD (5.8 mo vs 6.2 mo). The AA and anti-EGFR antibodies cohorts also had similar mTTD in the left-sided CRC subgroup (6.5 mo vs 6.2 mo), but not in the right-sided subgroup (5.6 mo vs 3.9 mo).&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Conclusions&lt;/h3&gt;&lt;p&gt;This is the first administrative data-based real-world evidence on treatment sequence and outcomes for patients with early recurrence CRC treated with FOLFIRI+AAs or FOLFIRI+ anti-EGFR antibodies after adjuvant FOLFOX/CAPOX therapy in Japan. Both regimens had similar TTD, but","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":"61 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834405","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}