Efficacy and safety of nanoparticle albumin‐bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non‐small cell lung cancer: A multicenter Phase 2 clinical trial

• Published in: Cancer medicine (Malden, MA) MA), 2023-06, Vol.12 (12), p.13041-13053
• Main Authors: Sonoda, Tomoaki, Umeda, Yukihiro, Demura, Yoshiki, Tada, Toshihiko, Nakashima, Koki, Anzai, Masaki, Yamaguchi, Makiko, Shimada, Akikazu, Ohi, Masahiro, Honjo, Chisato, Waseda, Yuko, Akai, Masaya, Ishizuka, Tamotsu
• Format: Article
• Language: English
• Subjects: Alanine transaminase; Albumin; Albumin-Bound Paclitaxel - adverse effects; Albumins - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Apoptosis; Aspartate aminotransferase; Brain research; Cancer therapies; Carcinoma, Non-Small-Cell Lung; Cell death; Chemotherapy; Clinical trials; Creatinine; Disease control; Drug dosages; Expected values; Hemoglobin; Humans; immune checkpoint inhibitor; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immunotherapy; Leukopenia; Lung cancer; Lung diseases; Lung Neoplasms; Magnetic resonance imaging; Medical prognosis; Metastasis; nab‐paclitaxel; Nanoparticles; Neutropenia; Neutropenia - chemically induced; Neutrophils; Non-small cell lung carcinoma; non‐small cell lung cancer; Paclitaxel; Paclitaxel - adverse effects; Patients; Peripheral neuropathy; programmed cell death 1 inhibitor; programmed death ligand 1 inhibitor; Review boards; Safety; Small cell lung carcinoma; Statistical analysis
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.5978

Background Whether immunotherapy improves the efficacy or worsens adverse events of subsequent chemotherapy remains unclear. We performed a Phase 2 study to evaluate the efficacy and safety of nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) as a treatment for advanced non‐small cell lung cancer (NSCLC) after treatment with programmed cell death 1 or programmed death ligand 1 [PD‐(L)1] inhibitor failure. Methods Nab‐paclitaxel (100 mg/m2) was administered on Days 1, 8, and 15 of a 28‐day cycle to patients with advanced NSCLC within 12 weeks after the failure of PD‐(L)1 inhibitor treatment. The primary endpoint was objective response rate (ORR) in all patients; the secondary endpoints were disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. Results Thirty cases were registered, and 29 cases were included in the analysis. The ORR was 55.2% (95% confidence interval [CI]: 28.1%–79.6%) and the DCR was 86.2% (95% CI: 65.9%–97.0%). The median PFS was 5.6 months (95% CI: 4.4–6.7 months), and PFS rates at 1‐ and 2‐year timepoints were 34.5% and 13.3%, respectively. The median OS was 11.9 months (95% CI: 0.8–23.0 months). Good performance status and responder of previous PD‐(L)1 inhibitor therapy were independent predictors of PFS. Grade 3 or higher toxicities included leukopenia (27.6%), neutropenia (31.0%), peripheral sensory neuropathy (6.9%), increased alanine aminotransferase and aspartate aminotransferase levels (3.4%), and interstitial lung disease (3.4%). Conclusions Nab‐paclitaxel therapy improved ORR after PD‐(L)1 inhibitor treatment failure with a durable response of 13% and acceptable toxicities in patients with advanced NSCLC.