Dataset Information

A Phase I/II Study of Neoadjuvant Cisplatin, Docetaxel, and Nintedanib for Resectable Non-Small Cell Lung Cancer.

ABSTRACT:

Purpose

Nintedanib enhances the activity of chemotherapy in metastatic non-small cell lung cancer (NSCLC). In this phase I/II study, we assessed safety and efficacy of nintedanib plus neoadjuvant chemotherapy, using major pathologic response (MPR) as primary endpoint.

Patients and methods

Eligible patients had stage IB (?4 cm)-IIIA resectable NSCLC. A safety run-in phase was followed by an expansion phase with nintedanib 200 mg orally twice a day (28 days), followed by three cycles of cisplatin (75 mg/m²), docetaxel (75 mg/m²) every 21 days plus nintedanib, followed by surgery. With 33 planned patients, the study had 90% power to detect an MPR increase from 15% to 35%.

Results

Twenty-one patients (stages I/II/III, N = 1/8/12) were treated. One of 15 patients treated with nintedanib 200 mg achieved MPR [7%, 95% confidence interval (CI), 0.2%-32%]. Best ORR in 20 evaluable patients was 30% (6/20, 95% CI, 12%-54%). Twelve-month recurrence-free survival and overall survival were 66% (95% CI, 47%-93%) and 91% (95% CI, 79%-100%), respectively. Most frequent treatment-related grade 3-4 toxicities were transaminitis and electrolyte abnormalities. On the basis of an interim analysis the study was discontinued for futility. Higher levels of CD3⁺ and cytotoxic CD3⁺CD8⁺ T cells were found in treated tumors of patients who were alive than in those who died (652.8 vs. 213.4 cells/mm², P = 0.048; 142.3 vs. 35.6 cells/mm², P = 0.018).

Conclusions

Although tolerated, neoadjuvant nintedanib plus chemotherapy did not increase MPR rate compared with chemotherapy historical controls. Additional studies of the combination in this setting are not recommended. Posttreatment levels of tumor-infiltrating T cells were associated with patient survival. Use of MPR facilitates the rapid evaluation of neoadjuvant therapies.See related commentary by Blakely and McCoach, p. 3499.

SUBMITTER: Cascone T

PROVIDER: S-EPMC7446232 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

A Phase I/II Study of Neoadjuvant Cisplatin, Docetaxel, and Nintedanib for Resectable Non-Small Cell Lung Cancer.

Cascone Tina T Sepesi Boris B Lin Heather Y HY Kalhor Neda N Parra Edwin R ER Jiang Mei M Godoy Myrna C B MCB Zhang Jianjun J Fossella Frank V FV Tsao Anne S AS Lam Vincent K VK Lu Charles C Mott Frank E FE Simon George R GR Antonoff Mara B MB Mehran Reza J RJ Rice David C DC Behrens Carmen C Weissferdt Annikka A Moran Cesar C Vaporciyan Ara A AA Lee J Jack JJ Swisher Stephen G SG Gibbons Don L DL Wistuba Ignacio I II William William N WN Heymach John V JV

Clinical cancer research : an official journal of the American Association for Cancer Research 20200319 14

<h4>Purpose</h4>Nintedanib enhances the activity of chemotherapy in metastatic non-small cell lung cancer (NSCLC). In this phase I/II study, we assessed safety and efficacy of nintedanib plus neoadjuvant chemotherapy, using major pathologic response (MPR) as primary endpoint.<h4>Patients and methods</h4>Eligible patients had stage IB (≥4 cm)-IIIA resectable NSCLC. A safety run-in phase was followed by an expansion phase with nintedanib 200 mg orally twice a day (28 days), followed by three cycle ...[more]

PMID: 32193228

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Dataset Information

A Phase I/II Study of Neoadjuvant Cisplatin, Docetaxel, and Nintedanib for Resectable Non-Small Cell Lung Cancer.

Purpose

Patients and methods

Results

Conclusions

Publications

A Phase I/II Study of Neoadjuvant Cisplatin, Docetaxel, and Nintedanib for Resectable Non-Small Cell Lung Cancer.

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