13 June 2024

Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study

 (JCO, IF: 45.3)

  • Solomon BJ, Liu G, Felip E, et al: Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study. J Clin Oncol JCO2400581, 2024

Purpose 目的

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.

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)和颅内活性。此,我们报告 CROWN 5 年随访后的长期结果。


Methods 研究方法

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.

96名ALK阳性NSCLC患者按1:1随机分配,接受洛拉替尼100mg,每天一次(n = 149)或克唑替尼250mg,每天两次(n = 147)。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。


Results 研究结果

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.

PFS的中位随访时间分别为60.2个月和55.1个月,洛拉替尼的中位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。


Conclusion 结论

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.



Trial registration: NCT03052608.