Trends in phase III randomized controlled clinical trials on the treatment of advanced non‐small‐cell lung cancer

Abstract

The objective of this review was to analyze trends in outcomes and in the quality of phase III randomized controlled trials on advanced NSCLC published between 2000 and 2012, selecting 76 trials from a total of 122 retrieved in a structured search. Over the study period, the number of randomized patients per trial increased by 14 per year (P = 0.178). The sample size significantly increased between 2000 and 2012 in trials of targeted agents (460.1 vs. 740.8 patients, P = 0.009), trials of >1 drug (360.4 vs. 584.8, P = 0.014), and those including patients with good performance status (675.3 vs. 425.6; P = 0.003). Quality of life was assessed in 46 trials (60.5%), and significant improvements were reported in 10 of these (21.7%). Platinum‐based regimens were the most frequently investigated (86.8% of trials). Molecular‐targeted agents were studied in 25.0% of chemotherapy arms, and the percentage of trials including these agents increased each year. The median (interquartile range) overall survival (MOS) was 9.90 (3.5) months with an increase of 0.384 months per year of publication (P < 0.001). A statistically significant improvement in MOS was obtained in only 13 (18.8%) trials. The median progression‐free survival was 4.9 (1.9) months, with a nonsignificant increase of 0.026 months per year (P > 0.05). There has been a continuous but modest improvement in the survival of patients with advanced NSCLC over the past 12 years. Nevertheless, the quality of clinical trials and the benefit in outcomes should be carefully considered before the incorporation of novel approaches into clinical practice.

The State of the Science in Patient-Reported Outcomes for Patients with Lung Cancer

“…A recent review for quality of phase III RCTs on advanced NSCLC found that 43.5% trials used a generic PRO, the EORTC QLQ C30; 50% used FACT-Lung Cancer; and 37% used EORTC QLQ-Lung Cancer. 88 This is relatively consistent with an earlier review, which found that 57% of trials used EORTC QLQ C30, while 23% used FACT for lung cancer patients. 10 The NCI has developed PRO tools for symptom measurement, including PRO-CTCAE and the Patient Reported Outcomes Measurement Information System (PROMIS).…”

Efficacy of chemoradiotherapy versus radiation alone in patients with inoperable locally advanced non–small-cell lung cancer

“…Further studies are needed to evaluate the effects of different chemotherapy regimens on other outcome measures such as health-related quality of life, an accurate predictor of survival [40] for which data remain scarce for NSCLC. [41]…”

Palliative thoracic radiation therapy for non-small cell lung cancer: 2018 Update of an American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline

“…Perhaps more important a limitation was the use of 5-fluorouracil alone as the CC agent; modern evidence overwhelmingly supports platinum-containing chemotherapy as being most active against NSCLC. 9 The 2 other RCTs were reported after publication of the original guideline. These trials draw different conclusions than Ball et al The first, Nawrocki et al, was a phase II RCT enrolling 99 patients with protocol-specified incurable stage III NSCLC in a 1:1 randomization between radiation alone (3000 cGy in 10 fractions) versus the same radiation dose delivered concurrent with the third of 3 cycles of cisplatin/vinorelbine (cisplatin 80 mg/m 2 on day 1, vinorelbine 25 mg/m 2 on days 1 and 8).…”