Randomized phase III study comparing the first-line chemotherapy regimens in patients with driver mutation-negative advanced non-small cell lung cancer and poor performance status complicated with chronic obstructive pulmonary disease

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD) with poor performance status (PS) are common in clinical practice with few related studies. Present studies have found that weekly low-dose docetaxel or gemcitabine combined with platinum is suitable for elderly or poor PS patients with advanced NSCLC. METHODS: Untreated advanced driver mutation-negative NSCLC patients with COPD and PS ≥2 were enrolled in this double-blind randomized trial. Both groups controlled their COPD symptoms according to the GOLD guidelines. The anti-tumor regimens included docetaxel (37.5 mg/m(2), D1, D8)/carboplatin (AUC 5.0) (DC group) and gemcitabine (1,000 mg/m(2), D1, D8)/carboplatin (AUC 5.0) (GC group) were used every 3 weeks with continuous chemotherapy for 4–6 cycles or until disease progression. The primary endpoints were progression-free survival (PFS), and overall survival (OS). RESULTS: Among the 52 patients (DC, n=25; GC, n=27), the median follow-up time was 12.3 months. There was no significant difference in tumor overall response rate (ORR; DC, 20.0% vs. GC, 22.2%, P=0.845) and disease control rate (DCR; DC, 72.0% vs. GC, 74.1%, P=0.064) between the 2 groups. The median PFS (GC, 6.5 vs. DC, 5.5 months; P=0.296) and the median OS (GC, 14.9 vs. DC, 12.3 months; P=0.548) of the GC group was slightly longer than the DC group. The main adverse reactions were myelosuppression and there were few adverse reactions of grade 3–4. Compared with the anti-tumor therapy only group in previous literature, the median PFS in this study was longer (6.2 months, 95% CI: 3.533–6.733 vs. 3.5 months, 95% CI: 2.432–4.568; P=0.589). There was also no significant difference in median OS and median PFS between the 2 groups (14.0 vs. 15.0 months, P=0.718). Chemotherapy cycle (P<0.001) was an independent prognostic factor for PFS, while chemotherapy cycle (P=0.011) and PS (P=0.041) were independent prognostic factors for OS. CONCLUSIONS: Weekly low-dose docetaxel or gemcitabine combined with carboplatin chemotherapy regimens can yield survival benefits and a tolerable safety profile in patients with driver mutation-negative advanced NSCLC and poor PS complicated with COPD, with no significant difference between the two regimens. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-15006164.