Dataset Information

A phase I study of the tyrosine kinase inhibitor anlotinib combined with platinum/pemetrexed-based chemotherapy in untreated nonsquamous non-small-cell lung cancer.

ABSTRACT:

Background

Anlotinib hydrochloride is an oral small molecule inhibitor of multiple tyrosine kinases, and it has been approved as a third-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with other chemotherapy regimens in patients with nonsquamous NSCLC.

Methods

This phase I study followed a 3 + 3 dose reduction design with three doses of anlotinib (12 mg, 10 mg, and 8 mg). Anlotinib was given at an initial dose of 12 mg with pemetrexed (500 mg/m²) plus cisplatin (75 mg/m²) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD), and secondary endpoints included progression-free survival (PFS) and overall survival (OS).

Results

A total of eight participants were enrolled. Dose-limiting toxicities (DLTs) were observed in two patients (pts) at anlotinib 12 mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred with 10 mg anlotinib, and the MTD was 10 mg. Among seven evaluable pts, four achieved a confirmed partial response (PR), and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95% CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs were observed during the treatment.

Conclusion

The feasible dose of anlotinib in combination with platinum/pemetrexed-based chemotherapy as a first-line regimen was 10 mg, which was well tolerated and showed promising antitumor activity in advanced nonsquamous NSCLC.

SUBMITTER: Huang M

PROVIDER: S-EPMC8993710 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

A phase I study of the tyrosine kinase inhibitor anlotinib combined with platinum/pemetrexed-based chemotherapy in untreated nonsquamous non-small-cell lung cancer.

Huang Meijuan M Liu Yongmei Y Yu Min M Li Yanying Y Zhang Yan Y Zhu Jiang J Li Li L Lu You Y Lu You Y

Investigational new drugs 20211101 2

<h4>Background</h4>Anlotinib hydrochloride is an oral small molecule inhibitor of multiple tyrosine kinases, and it has been approved as a third-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with other chemotherapy regimens in patients with nonsquamous NSCLC.<h4>Methods</h4>This phase I study followed a 3 + 3 dose reduction design with three doses of anlotini ...[more]

PMID: 34724131

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Dataset Information

A phase I study of the tyrosine kinase inhibitor anlotinib combined with platinum/pemetrexed-based chemotherapy in untreated nonsquamous non-small-cell lung cancer.

Background

Methods

Results

Conclusion

Publications

A phase I study of the tyrosine kinase inhibitor anlotinib combined with platinum/pemetrexed-based chemotherapy in untreated nonsquamous non-small-cell lung cancer.

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