1874 - A prospective phase II trial of carboplatin (CBDCA) and nab-paclitaxel (nabPTX) for advanced non-small cell lung cancer (NSCLC) with interstitial lung disease (ILD)

Background

Because of the high risk of exacerbation of ILD, patients with concomitant advanced NSCLC and ILD have been excluded from most clinical trials of chemotherapy, despite around 10% of all NSCLC cases. This study prospectively evaluated the efficacy and safety of nab-paclitaxel in combination with CBDCA in advanced NSCLC patients with ILD.

Methods

Enrolled patients had treatment-naïve, advanced NSCLC with ILD. Patients received 100 mg/m²nabPTX weekly and CBDCA at area under the concentration-time curve (AUC) 6 once every 3 weeks for 4-6 cycles. The primary endpoint was overall response rate (ORR); secondary endpoints included toxicity, progression-free survival (PFS) and overall survival (OS).

Results

Thirty-six patients were enrolled between April 2014 and September 2017. Sixteen patients (44.4%) had an adenocarcinoma, followed by 15 (41.7%) squamous cell carcinoma, and 5 (13.9%) non-small cell carcinoma. The median number of cycles administered were 4 (range: 1-6). The ORR was 55.6% (95% confidence interval [CI]: 39.6-70.5). The median PFS and OS were 5.3 months (95% CI: 3.9-8.2) and 15.4 months (95% CI: 9.4-18.7). There was no significant difference between two groups, however, numerically better treatment outcomes were observed in the Sq group: the ORR was 66.7% (95% CI: 41.7–84.8) in the Sq group compared with 47.6% (95% CI: 28.3–67.6) in the Non-Sq group (P = 0.254); median PFS was 8.2 months (95% CI: 4.0–10.2) in the Sq group vs. 4.1 months (95% CI: 3.3-5.4) in the Non-Sq group (HR, 0.60 [95% CI, 0.30–1.20]; p = 0.15); median OS was 16.8 months (95% CI: 9.8–not reached) in the Sq group vs. 11.9 months (95% CI: 7.3-17.4) in the Non-Sq group (HR, 0.56 [95% CI, 0.24–1.28]; p = 0.17). Two patients (5.6%) experienced grade ≥2 pneumonitis and one patient (2.8%) died. After the protocol treatment, 24 patients (66.7%) underwent second-line therapy. Most preferred regimen were S-1 (n = 12, 50%), followed by vinorelbine (n = 4, 16.7%) and docetaxel (n = 3, 12.5%).

Conclusions

This is the first prospective phase II trial of weekly nabPTX in combination with CBDCA in advanced NSCLC patients with ILD. This treatment showed favorable efficacy and was well tolerated.

Clinical trial identification

UMIN000012901.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Harada: Honoraria (institution): GlaxoSmithKline K.K.; Honoraria (institution): Hisamitsu Pharmaceutical Co.,Inc; Honoraria (institution): Boehrnger INgelheim. S. Oizumi: Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Chugai Pharmaceutical Co.; Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Eli Lilly. Y. Fujita: Honoraria (institution): Eli Lilly; Honoraria (institution): Chugai Pharma; Honoraria (institution): Taiho Pharmaceutical; Honoraria (institution): Pfizer; Honoraria (institution): Hisamitsu Pharmaceutical; Honoraria (institution): Novartis; Honoraria (institution): Ono Pharmaceutical. All other authors have declared no conflicts of interest.