A phase I/II trial of weekly nab-paclitaxel for pretreated non-small-cell lung cancer patients without epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement.

Abstract

AIM:

We investigated the efficacy, safety and optimal schedule of nanoparticle albumin-bound paclitaxel monotherapy as second- or third-line treatment for non-small-cell lung cancer patients without epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement.

METHODS:

Patients with pretreated advanced non-small-cell lung cancer without epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement were included. The patients were administered 100 mg/m2 of nanoparticle albumin-bound paclitaxel on days 1, 8, 15 and 22 (level 0) or on days 1, 8 and 15 (level -1) every 4 weeks during phase I of the trial. The primary endpoint was objective response rate. The estimated objective response rate was 15% and the threshold was 5% with an α error of 0.05 and β error of 0.2 in phase II.

RESULTS:

The recommended schedule was determined as level -1 in phase I. The characteristics of the 55 patients enrolled in phase II were as follows: median age = 66 years, male/female = 40/15, second/third line = 34/21 and adenocarcinoma/squamous cell carcinoma/large cell carcinoma/others = 34/17/2/2. Objective response rate was 7.3% (95% confidence interval, 2.0-17.6%). Median progression-free survival was 3.4 months. Treatment-related grade 3 or 4 toxicities were neutropenia (36.4%), febrile neutropenia (5.5%) and pulmonary infection (3.6%). Three patients had grade 2 pneumonitis and one treatment-related death occurred due to adult respiratory distress syndrome.

CONCLUSION:

This study failed to meet predefined primary endpoints for pretreated patients with advanced non-small-cell lung cancer without epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement.

• Authors: Daijiro Harada, Toshiyuki Kozuki, Naoyuki Nogami, Akihiro Bessho, Shinobu Hosokawa, Nobuaki Fukamatsu, Katsuyuki Hotta, Kadoaki Ohashi, Toshio Kubo, Hiroshige Yoshioka, Toshihide Yokoyama, Naoyuki Sone, Shoichi Kuyama, Kenichiro Kudo, Masayuki Yasugi, Nagio Takigawa, Isao Oze, Katsuyuki Kiura
• Journal: Asia-Pacific journal of clinical oncology (Asia Pac J Clin Oncol) Vol. 15 Issue 4 Pg. 250-256 (Aug 2019) ISSN: 1743-7563 [Electronic] Australia
• PMID: 30938103 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
• Copyright: © 2019 The Authors. Asia-Pacific Journal of Clinical Oncology Published by John Wiley & Sons Australia, Ltd.

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Anaplastic Lymphoma Kinase
• ErbB Receptors
• Paclitaxel

Topics

• Aged
• Albumins (pharmacology, therapeutic use)
• Anaplastic Lymphoma Kinase (genetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• ErbB Receptors (genetics)
• Female
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Mutation
• Paclitaxel (pharmacology, therapeutic use)