Treatment rationale and design of the PROLONG study: safety and efficacy of pembrolizumab as first-line therapy for elderly patients with non-small cell lung cancer.

BACKGROUND: Pembrolizumab is recommended as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) and a Programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥50% without driver mutations. However, the safety and efficacy were not investigated among patients who were ≥75 years old. METHODS: This open-label single-arm phase II study is designed to evaluate pembrolizumab as first-line therapy for patients who are ≥75 years old with advanced NSCLC and a PD-L1 TPS of ≥50% without driver mutations. The primary endpoint is progression-free survival, and the secondary endpoints are overall survival, objective response rate, safety, and quality of life. Recruitment started in October 2017 and is expected to continue for approximately 3 years. CONCLUSIONS: Given the currently poor prognosis of elderly patients with advanced NSCLC, we hope that the findings of this study will facilitate more effective treatment in this setting.

Carboplatin plus Weekly Paclitaxel Combined with Bevacizumab as First-line Treatment for Non-small Cell Lung Cancer.

AIM: We aimed to evaluate the efficacy and safety of carboplatin plus weekly paclitaxel with bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB/IV or postoperative recurrent NSCLC (n=33) were treated with carboplatin (area under the curve of 6) on day 1; paclitaxel (80 mg/m2) on days 1, 8, and 15; and bevacizumab (15 mg/kg) on day 1 repeated every 4 weeks, for four to six cycles; followed by maintenance bevacizumab (15 mg/kg) every 3 weeks. RESULTS: The overall response rate was 76%. The median progression-free survival and overall survival were 8.4 months and 22.2 months, respectively. Grade 3-4 toxicities included neutropenia in 55% of patients, anemia in 18%, febrile neutropenia in 12%, and anorexia in 9%. No treatment-related deaths were observed. CONCLUSION: Carboplatin plus weekly paclitaxel with bevacizumab was effective and well tolerated by patients with advanced NSCLC.

[Adverse events during pemetrexed administration caused by concomitant nonsteroid anti-inflammatory therapy].

Pemetrexed, a folate metabolic antagonist, is considered to be effective against plural mesotheliomas, non-small cell lung cancer, and especially for non-squamous cell cancer. However, it has been reported to have adverse interactions with nonsteroid anti-inflammatory drugs(NSAIDs). In the present study, we compared the incidence of adverse events between patients receiving pemetrexed therapy with and without concomitant NSAID administration. No significant difference in the incidence of hematotoxic events of Grade 3 or worse was observed. As for the incidence of non-hematotoxic events, the increase in the amount of creatinine, namely a severe adverse effect of Grade 2 or more, was significantly higher in the combined therapy group (p=0.018). No other significant differences were noted for other adverse events. A creatinine increase to Grade 2 or greater developed significantly earlier in the combined group(median value, 12.7 courses; p=0.0063). Our results suggest that renal dysfunction may easily develop as a result of continued pemetrexed administration combined with NSAID therapy. Therefore, it is necessary to take precautions against adverse side effects such as renal dysfunction when combining pemetrexed with NSAID therapy, by conducting periodic examinations.