TY - JOUR
T1 - Intracranial efficacy of selpercatinib in RET fusion-positive non–small cell lung cancers on the LIBRETTO-001 trial
AU - Subbiah, Vivek
AU - Gainor, Justin F.
AU - Oxnard, Geoffrey R.
AU - Tan, Daniel S.W.
AU - Owen, Dwight H.
AU - Cho, Byoung Chul
AU - Loong, Herbert H.
AU - McCoach, Caroline E.
AU - Weiss, Jared
AU - Kim, Yu Jung
AU - Bazhenova, Lyudmila
AU - Park, Keunchil
AU - Daga, Haruko
AU - Besse, Benjamin
AU - Gautschi, Oliver
AU - Rolfo, Christian
AU - Zhu, Edward Y.
AU - Kherani, Jennifer F.
AU - Huang, Xin
AU - Kang, Suhyun
AU - Drilon, Alexander
N1 - Publisher Copyright:
© 2021 The Authors; Published by the American Association for Cancer Research.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Purpose: We report the intracranial efficacy of selpercatinib, a highly potent and selective RET inhibitor, approved in the United States for RET fusion-positive non–small cell lung cancers (NSCLC). Patients and Methods: In the global phase 1/2 LIBRETTO-001 trial (NCT03157128) in advanced RET-altered solid tumors, selpercatinib was dosed orally (160 mg twice every day) in 28-day cycles. Patients with baseline intracranial metastases had MRI/CT scans every 8 weeks for 1 year (12 weeks thereafter). In this preplanned analysis of patients with RET fusion-positive NSCLC with baseline intracranial metastases, the primary endpoint was independently assessed intracranial objective response rate (ORR) per RECIST 1.1. Secondary endpoints included intracranial disease control rate, intracranial duration of response, and intracranial progression-free survival (PFS) independently reviewed. Results: Eighty patients with NSCLC had brain metastases at baseline. Patients were heavily pretreated (median ¼ 2 systemic therapies, range ¼ 0–10); 56% of patients received ≥1 course of intracranial radiation (14% whole brain radiotherapy, 45% stereotactic radiosurgery). Among 22 patients with measurable intracranial disease at baseline, intracranial ORR was 82% [95% confidence interval (CI), 60–95], including 23% with complete responses. Among all intracranial responders (measurable and nonmeasurable, n ¼ 38), median duration of intracranial response was not reached (95% CI, 9.3–NE) at a median duration of follow-up of 9.5 months (IQR ¼ 5.7, 12.0). At 12 months, 55% of intracranial responses were ongoing. In all 80 patients, median intracranial PFS was 13.7 months (95% CI, 10.9–NE) at a median duration of followup of 11.0 months (IQR ¼ 7.4, 16.5). No new safety signals were revealed in patients with brain metastases compared with the full NSCLC trial population. Conclusions: Selpercatinib has robust and durable intracranial efficacy in patients with RET fusion-positive NSCLC.
AB - Purpose: We report the intracranial efficacy of selpercatinib, a highly potent and selective RET inhibitor, approved in the United States for RET fusion-positive non–small cell lung cancers (NSCLC). Patients and Methods: In the global phase 1/2 LIBRETTO-001 trial (NCT03157128) in advanced RET-altered solid tumors, selpercatinib was dosed orally (160 mg twice every day) in 28-day cycles. Patients with baseline intracranial metastases had MRI/CT scans every 8 weeks for 1 year (12 weeks thereafter). In this preplanned analysis of patients with RET fusion-positive NSCLC with baseline intracranial metastases, the primary endpoint was independently assessed intracranial objective response rate (ORR) per RECIST 1.1. Secondary endpoints included intracranial disease control rate, intracranial duration of response, and intracranial progression-free survival (PFS) independently reviewed. Results: Eighty patients with NSCLC had brain metastases at baseline. Patients were heavily pretreated (median ¼ 2 systemic therapies, range ¼ 0–10); 56% of patients received ≥1 course of intracranial radiation (14% whole brain radiotherapy, 45% stereotactic radiosurgery). Among 22 patients with measurable intracranial disease at baseline, intracranial ORR was 82% [95% confidence interval (CI), 60–95], including 23% with complete responses. Among all intracranial responders (measurable and nonmeasurable, n ¼ 38), median duration of intracranial response was not reached (95% CI, 9.3–NE) at a median duration of follow-up of 9.5 months (IQR ¼ 5.7, 12.0). At 12 months, 55% of intracranial responses were ongoing. In all 80 patients, median intracranial PFS was 13.7 months (95% CI, 10.9–NE) at a median duration of followup of 11.0 months (IQR ¼ 7.4, 16.5). No new safety signals were revealed in patients with brain metastases compared with the full NSCLC trial population. Conclusions: Selpercatinib has robust and durable intracranial efficacy in patients with RET fusion-positive NSCLC.
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U2 - 10.1158/1078-0432.CCR-21-0800
DO - 10.1158/1078-0432.CCR-21-0800
M3 - Article
C2 - 34088726
AN - SCOPUS:85111700467
SN - 1078-0432
VL - 27
SP - 4160
EP - 4167
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -