TY - JOUR
T1 - Asian Subgroup Analysis of the Randomized Phase 3 CROWN Study of First-Line Lorlatinib Versus Crizotinib in Advanced ALK-Positive NSCLC
AU - Zhou, Qing
AU - Soo, Ross A.
AU - Chang, Gee Chen
AU - Chiu, Chao Hua
AU - Hayashi, Hidetoshi
AU - Kim, Sang We
AU - Teraoka, Shunsuke
AU - Goto, Yasushi
AU - Zhou, Jianying
AU - Ho-Fun Lee, Victor
AU - Kim, Dong Wan
AU - Han, Baohui
AU - Chung Man Ho, James
AU - Lin, Chia Chi
AU - Lu, Shun
AU - Polli, Anna
AU - Calella, Anna Maria
AU - Martini, Jean François
AU - Wong, Chew Hooi
AU - Mok, Tony
AU - Kim, Hye Ryun
AU - Wu, Yi Long
N1 - Funding Information:
This study was sponsored by Pfizer Inc. Editorial and medical writing support was provided by Annette Smith, PhD, and Laura George, PhD, CMPP, of CMC AFFINITY, McCann Health Medical Communications, and Alana Dorfstatter, PhD, of ClinicalThinking, Inc., and was funded by Pfizer . The authors thank the participating patients and their families, including the research nurses, trial coordinators, and operations staff. The authors also thank Deborah Shepard for support with the biomarker analyses for this study. All authors critically reviewed the manuscript and approved the final version for submission.
Publisher Copyright:
© 2023 The Authors
PY - 2023/5
Y1 - 2023/5
N2 - Introduction: Lorlatinib is a potent, third-generation inhibitor of ALK. In the planned interim analysis of the ongoing, phase 3, randomized, global CROWN trial (NCT03052608), lorlatinib resulted in significantly longer progression-free survival than crizotinib in patients with previously untreated, advanced, ALK-positive NSCLC. Here, we present a subgroup analysis of Asian patients in the CROWN study. Methods: Patients received lorlatinib 100 mg once daily or crizotinib 250 mg twice daily. The primary end point was progression-free survival assessed by blinded independent central review. Objective response rate (ORR), intracranial ORR, safety, and select biomarkers were secondary end points. Results: At data cutoff (September 20, 2021), 120 patients were included in the Asian intention-to-treat subgroup (lorlatinib n = 59; crizotinib n = 61). At 36 months, 61% (95% confidence interval [CI]: 47–72) and 25% (95% CI: 12–41) of patients in the lorlatinib and crizotinib groups, respectively, were alive without disease progression (hazard ratio for disease progression by blinded independent central review or death: 0.40; 95% CI: 0.23–0.71). ORR was 78% (95% CI: 65–88) versus 57% (95% CI: 44–70) for patients treated with lorlatinib and crizotinib, respectively. In patients with measurable, nonmeasurable, or both measurable and nonmeasurable brain metastases at baseline, intracranial ORR was 73% (95% CI: 39–94) versus 20% (95% CI: 4–48) for patients treated with lorlatinib and crizotinib, respectively. The definition of nonmeasurable brain metastases is: a brain lesion less than 10 mm in MRI scan is defined as nonmeasurable brain metastasi based on RECIST criteria (Clinical trial evaluation criteria). Hypercholesterolemia, hypertriglyceridemia, and edema were the most frequently reported adverse events with lorlatinib. Conclusions: Lorlatinib efficacy and safety in the Asian subgroup of CROWN were consistent with those in the overall population.
AB - Introduction: Lorlatinib is a potent, third-generation inhibitor of ALK. In the planned interim analysis of the ongoing, phase 3, randomized, global CROWN trial (NCT03052608), lorlatinib resulted in significantly longer progression-free survival than crizotinib in patients with previously untreated, advanced, ALK-positive NSCLC. Here, we present a subgroup analysis of Asian patients in the CROWN study. Methods: Patients received lorlatinib 100 mg once daily or crizotinib 250 mg twice daily. The primary end point was progression-free survival assessed by blinded independent central review. Objective response rate (ORR), intracranial ORR, safety, and select biomarkers were secondary end points. Results: At data cutoff (September 20, 2021), 120 patients were included in the Asian intention-to-treat subgroup (lorlatinib n = 59; crizotinib n = 61). At 36 months, 61% (95% confidence interval [CI]: 47–72) and 25% (95% CI: 12–41) of patients in the lorlatinib and crizotinib groups, respectively, were alive without disease progression (hazard ratio for disease progression by blinded independent central review or death: 0.40; 95% CI: 0.23–0.71). ORR was 78% (95% CI: 65–88) versus 57% (95% CI: 44–70) for patients treated with lorlatinib and crizotinib, respectively. In patients with measurable, nonmeasurable, or both measurable and nonmeasurable brain metastases at baseline, intracranial ORR was 73% (95% CI: 39–94) versus 20% (95% CI: 4–48) for patients treated with lorlatinib and crizotinib, respectively. The definition of nonmeasurable brain metastases is: a brain lesion less than 10 mm in MRI scan is defined as nonmeasurable brain metastasi based on RECIST criteria (Clinical trial evaluation criteria). Hypercholesterolemia, hypertriglyceridemia, and edema were the most frequently reported adverse events with lorlatinib. Conclusions: Lorlatinib efficacy and safety in the Asian subgroup of CROWN were consistent with those in the overall population.
KW - Anaplastic lymphoma kinase
KW - Lorlatinib
KW - Non–small cell lung cancer
KW - Phase 3
KW - Progression-free survival
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U2 - 10.1016/j.jtocrr.2023.100499
DO - 10.1016/j.jtocrr.2023.100499
M3 - Article
AN - SCOPUS:85159134819
SN - 2666-3643
VL - 4
JO - JTO Clinical and Research Reports
JF - JTO Clinical and Research Reports
IS - 5
M1 - 100499
ER -
