Benjamin J Solomon, Geoffrey Liu, Enriqueta Felip, Tony S K Mok, Ross A Soo, Julien Mazieres, Alice T Shaw, Filippo de Marinis, Yasushi Goto, Yi-Long Wu, Dong-Wan Kim, Jean-François Martini, Rossella Messina, Jolanda Paolini, Anna Polli, Despina Thomaidou, Francesca Toffalorio, Todd M Bauer
{"title":"洛拉替尼与克唑替尼在 ALK 阳性晚期非小细胞肺癌患者中的应用:III 期 CROWN 研究的 5 年结果。","authors":"Benjamin J Solomon, Geoffrey Liu, Enriqueta Felip, Tony S K Mok, Ross A Soo, Julien Mazieres, Alice T Shaw, Filippo de Marinis, Yasushi Goto, Yi-Long Wu, Dong-Wan Kim, Jean-François Martini, Rossella Messina, Jolanda Paolini, Anna Polli, Despina Thomaidou, Francesca Toffalorio, Todd M Bauer","doi":"10.1200/JCO.24.00581","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Lorlatinib improved progression-free survival (PFS) and intracranial activity versus crizotinib in patients with previously untreated, advanced, <i>ALK</i>-positive non-small cell lung cancer (NSCLC) in the phase III CROWN study. Here, we report long-term outcomes from CROWN after 5 years of follow-up.</p><p><strong>Methods: </strong>Two hundred ninety-six patients with <i>ALK</i>-positive NSCLC were randomly assigned 1:1 to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses.</p><p><strong>Results: </strong>With a median follow-up for PFS of 60.2 and 55.1 months, respectively, median PFS was not reached (NR [95% CI, 64.3 to NR]) with lorlatinib and 9.1 months (95% CI, 7.4 to 10.9) with crizotinib (hazard ratio [HR], 0.19 [95% CI, 0.13 to 0.27]); 5-year PFS was 60% (95% CI, 51 to 68) and 8% (95% CI, 3 to 14), respectively. Median time to intracranial progression was NR (95% CI, NR to NR) with lorlatinib and 16.4 months (95% CI, 12.7 to 21.9) with crizotinib (HR, 0.06 [95% CI, 0.03 to 0.12]). Safety profile was consistent with that in prior analyses. Emerging new <i>ALK</i> resistance mutations were not detected in circulating tumor DNA collected at the end of lorlatinib treatment.</p><p><strong>Conclusion: </strong>After 5 years of follow-up, median PFS has yet to be reached in the lorlatinib group, corresponding to the longest PFS ever reported with any single-agent molecular targeted treatment in advanced NSCLC and across all metastatic solid tumors. These results coupled with prolonged intracranial efficacy and absence of new safety signals represent an unprecedented outcome for patients with advanced <i>ALK</i>-positive NSCLC and set a new benchmark for targeted therapies in cancer.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3400-3409"},"PeriodicalIF":42.1000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458101/pdf/","citationCount":"0","resultStr":"{\"title\":\"Lorlatinib Versus Crizotinib in Patients With Advanced <i>ALK</i>-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study.\",\"authors\":\"Benjamin J Solomon, Geoffrey Liu, Enriqueta Felip, Tony S K Mok, Ross A Soo, Julien Mazieres, Alice T Shaw, Filippo de Marinis, Yasushi Goto, Yi-Long Wu, Dong-Wan Kim, Jean-François Martini, Rossella Messina, Jolanda Paolini, Anna Polli, Despina Thomaidou, Francesca Toffalorio, Todd M Bauer\",\"doi\":\"10.1200/JCO.24.00581\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Lorlatinib improved progression-free survival (PFS) and intracranial activity versus crizotinib in patients with previously untreated, advanced, <i>ALK</i>-positive non-small cell lung cancer (NSCLC) in the phase III CROWN study. Here, we report long-term outcomes from CROWN after 5 years of follow-up.</p><p><strong>Methods: </strong>Two hundred ninety-six patients with <i>ALK</i>-positive NSCLC were randomly assigned 1:1 to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses.</p><p><strong>Results: </strong>With a median follow-up for PFS of 60.2 and 55.1 months, respectively, median PFS was not reached (NR [95% CI, 64.3 to NR]) with lorlatinib and 9.1 months (95% CI, 7.4 to 10.9) with crizotinib (hazard ratio [HR], 0.19 [95% CI, 0.13 to 0.27]); 5-year PFS was 60% (95% CI, 51 to 68) and 8% (95% CI, 3 to 14), respectively. Median time to intracranial progression was NR (95% CI, NR to NR) with lorlatinib and 16.4 months (95% CI, 12.7 to 21.9) with crizotinib (HR, 0.06 [95% CI, 0.03 to 0.12]). Safety profile was consistent with that in prior analyses. Emerging new <i>ALK</i> resistance mutations were not detected in circulating tumor DNA collected at the end of lorlatinib treatment.</p><p><strong>Conclusion: </strong>After 5 years of follow-up, median PFS has yet to be reached in the lorlatinib group, corresponding to the longest PFS ever reported with any single-agent molecular targeted treatment in advanced NSCLC and across all metastatic solid tumors. These results coupled with prolonged intracranial efficacy and absence of new safety signals represent an unprecedented outcome for patients with advanced <i>ALK</i>-positive NSCLC and set a new benchmark for targeted therapies in cancer.</p>\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":\" \",\"pages\":\"3400-3409\"},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458101/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/JCO.24.00581\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO.24.00581","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/31 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的:在III期CROWN研究中,对于既往未经治疗的晚期ALK阳性非小细胞肺癌(NSCLC)患者,与克唑替尼相比,洛拉替尼可改善患者的无进展生存期(PFS)和颅内活动度。在此,我们报告 CROWN 5 年随访后的长期结果:296名ALK阳性NSCLC患者按1:1比例随机分配,接受lorlatinib 100毫克,每天一次(149人)或克唑替尼250毫克,每天两次(147人)。这份事后分析报告介绍了研究者评估的最新疗效结果、安全性和生物标志物分析:中位随访PFS分别为60.2个月和55.1个月,lorlatinib的中位PFS未达到(NR [95% CI, 64.3 to NR]),克唑替尼的中位PFS为9.1个月(95% CI, 7.4 to 10.9)(危险比[HR],0.19 [95% CI, 0.13 to 0.27]);5年PFS分别为60%(95% CI, 51 to 68)和8%(95% CI, 3 to 14)。洛拉替尼中位颅内进展时间为NR(95% CI,NR至NR),克唑替尼为16.4个月(95% CI,12.7至21.9)(HR,0.06 [95% CI,0.03至0.12])。安全性与之前的分析结果一致。在罗拉替尼治疗结束时收集的循环肿瘤DNA中未检测到新的ALK耐药突变:结论:经过5年的随访,lorlatinib组的中位生存期尚未达到,这是晚期NSCLC单药分子靶向治疗和所有转移性实体瘤中有报道的最长生存期。这些结果加上延长的颅内疗效和无新的安全性信号,代表了晚期ALK阳性NSCLC患者前所未有的治疗结果,为癌症靶向治疗树立了新的标杆。
Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study.
Purpose: Lorlatinib improved progression-free survival (PFS) and intracranial activity versus crizotinib in patients with previously untreated, advanced, ALK-positive non-small cell lung cancer (NSCLC) in the phase III CROWN study. Here, we report long-term outcomes from CROWN after 5 years of follow-up.
Methods: Two hundred ninety-six patients with ALK-positive NSCLC were randomly assigned 1:1 to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses.
Results: With a median follow-up for PFS of 60.2 and 55.1 months, respectively, median PFS was not reached (NR [95% CI, 64.3 to NR]) with lorlatinib and 9.1 months (95% CI, 7.4 to 10.9) with crizotinib (hazard ratio [HR], 0.19 [95% CI, 0.13 to 0.27]); 5-year PFS was 60% (95% CI, 51 to 68) and 8% (95% CI, 3 to 14), respectively. Median time to intracranial progression was NR (95% CI, NR to NR) with lorlatinib and 16.4 months (95% CI, 12.7 to 21.9) with crizotinib (HR, 0.06 [95% CI, 0.03 to 0.12]). Safety profile was consistent with that in prior analyses. Emerging new ALK resistance mutations were not detected in circulating tumor DNA collected at the end of lorlatinib treatment.
Conclusion: After 5 years of follow-up, median PFS has yet to be reached in the lorlatinib group, corresponding to the longest PFS ever reported with any single-agent molecular targeted treatment in advanced NSCLC and across all metastatic solid tumors. These results coupled with prolonged intracranial efficacy and absence of new safety signals represent an unprecedented outcome for patients with advanced ALK-positive NSCLC and set a new benchmark for targeted therapies in cancer.
期刊介绍:
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.