The efficacy of 40 mg versus dose de-escalation to less than 40 mg of afatinib (Giotrif) as the first-line therapy for patients with primary lung adenocarcinoma harboring favorable epidermal growth factor mutations

Abstract

The choice of a first-line therapy for lung cancer is a crucial decision that can impact the survival as well as the quality of life of a patient. Inhibitors of epidermal growth factor receptor (EGFR) such as afatinib, erlotinib, and gefitinib have previously been used to treat non-small cell lung cancer harboring favorable EGFR mutations. Although afatinib has greater efficacy than other EGFR inhibitors, adverse events related to its use can result in the discontinuation of the therapy. In this study, we compared the therapeutic efficacy in lung cancer patients of a regimen of 40 mg/day of afatinib with that of a lower dose regimen of <40 mg/day resulting either from a lower starting dose of 30 mg/day or dose adjustment. Seventy-nine patients were treated with 40 mg/day and 67 received de-escalated doses of <40 mg/day. There was no significant difference in the clinical characteristics of the two groups except that the proportion of patients with a body weight of 50 kg or more was greater in the 40 mg/day group. Otherwise, there were no significant differences between the two groups in the average time to treatment failure (TTF), the rates at which the administration of a second-line therapy was necessary, or the frequency and severity of adverse events. Overall, these results suggest that it is possible to calibrate the dosage of afatinib to suit individual patient parameters such as low body weight, and that such calibration can be advised based on the given patient’s individual experience of the drug.

Clinical analysis of EGFR‐positive non‐small cell lung cancer patients treated with first‐line afatinib: A Nagano Lung Cancer Research Group

“…In a real‐world cohort study in Taiwan, there was no significant difference in median PFS in the first six months between the 40 mg and < 40 mg groups (12.0 vs. 11.0 months, respectively) . In a retrospective analysis of the efficacy of 40 mg versus dose reduction to < 40 mg of afatinib, there were no significant differences between the groups in the median time to treatment failure (405 vs. 472 days, respectively; P = 0.2271) . In our study, the median PFS rates in the < 40 mg and 40 mg groups were 14.2 and 15.7 months, respectively.…”

Efficacy and Safety of <b><i>ALK</i></b> Tyrosine Kinase Inhibitors in Elderly Patients with Advanced <b><i>ALK</i></b>-Positive Non-Small Cell Lung Cancer: Findings from the Real-Life Cohort

“…Similar efficacy despite the lower dose intensity with each of the ALK TKIs assessed might reflect the slower drug metabolism in the elderly as compared to younger individuals, resulting in similar exposure levels – as it was observed with afatinib, an epidermal growth factor receptor TKI [18, 19]. …”

Synergistic antitumor activity of low-dose c-Met tyrosine kinase inhibitor and sorafenib on human non-small cell lung cancer cells

“…Briefly, 1x10 5 cells were seeded into 6-well plates and incubated with designated concentrations of Sorafenib and/or PF-2341066 dissolved in DMSO (0.5 µM PF, 2.5 µM Sora, 0.5 µM PF + 2.5 µM Sora) for 24 h at 37˚C and 5% CO 2 . Then, the cells were harvested.…”

“…Migration assays were performed using polycarbonate membrane chambers (pore size, 8.0 µm; EMD Millipore, Billerica, MA, USA) as previously demonstrated (27). Briefly, NCI-H1993 cells (1x10 5 ) were suspended in 100 µl RPMI-1640 medium containing 1.5% FBS were added to the upper chambers. The lower compartments of the chamber were filled with RPMI-1640 medium containing 15% FBS and the designated concentrations of Sorafenib and/or PF-2341066 dissolved in DMSO (0.5 µΜ PF, 2.5 µΜ Sora, 0.5 µΜ PF + 2.5 µΜ Sora).…”

“…The first-line standard treatment for NSCLC, including surgery, chemotherapy and radiotherapy, is selected depending on the disease and patient characteristics (4). Currently, platinum-based regimens are first-line chemotherapies; single-agent docetaxel, pemetrexed or erlotinib are prominent second-line therapies (5). However, no response or resistance to conventional chemotherapies is a problem when studying the pathological processes and new therapeutic strategies for lung tumors (6).…”