Dexketoprofen Trometamol/Tramadol Hydrochloride

Dabrafenib plus trametinib (Dab + Tram) is an approved targeted therapy in patients with BRAF ^V600+ mutated metastatic non-small cell lung cancer (NSCLC). Here, we report the efficacy, safety, and quality of life (QoL) results of Dab + Tram treatment in Chinese patients with BRAF ^V600E mutation-positive metastatic NSCLC.

This is a single-arm, open-label, multicentre, phase II study (NCT04452877). Patients received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily. The primary endpoint was overall response rate (ORR) by central independent review per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria. Secondary endpoints included ORR by investigator assessment, progression-free survival (PFS), duration of response (DOR), overall survival (OS), safety, tolerability, and QoL.

At the data cut-off (March 11, 2021), 18 of 20 enrolled patients were still receiving treatment. The median age was 64 years; majority were female (55%), non-smokers (55%), and had ≥3 metastatic sites (70%). Nine patients received prior anticancer therapy in a therapeutic or metastatic setting. The median duration of follow-up was 5 months. The ORR by both central and investigator assessment was 75% [95% confidence interval (CI): 50.9-91.3%]. The median DOR, PFS, and OS were not reached/estimable at the cut-off date. The most common treatment-related adverse events (AEs) (all grades, in ≥30% of patients) were pyrexia, increased aspartate aminotransferase (AST), decreased neutrophil count, and decreased white blood cell (WBC) count. The self-reported QoL was improved or maintained during the treatment period.

Dab + Tram treatment is safe, effective, and can preserve or improve QoL in majority of Chinese patients with BRAF ^V600E mutation-positive metastatic NSCLC. The results are consistent with the global phase II study.

Dexketoprofen/tramadol 25/75 mg (DKP/TRAM) is a fixed-dose combination of a cyclooxygenase inhibitor and opioid receptor agonist. To better understand the efficacy and safety of DKP/TRAM in the treatment of moderate to severe acute lower back pain (LBP) with or without radiculopathy, we carried out a large explorative phase IV international, multicenter, prospective, randomized, double-blind, parallel group, placebo-controlled study (DANTE).

A total of 538 patients with or without a history of LBP and experiencing acute LPB of moderate to severe intensity [Numerical Rating Scale-Pain Intensity (NRS-PI) score > 5] were randomized 4:4:1:1 to DKP/TRAM 25/75 mg every 8 h (n = 211), tramadol (TRAM) 100 mg (n = 207), placebo-matched DKP/TRAM (n = 59), or placebo-matched TRAM (n = 61).

The proportion of patients achieving the primary endpoint, defined as the time to first achieve NRS-PI score < 4 or pain intensity reduction ≥ 30% from drug intake up to 8 h after the first dose, was higher in the DKP/TRAM arm than in the placebo group, but the difference was not statistically significant (46.1% vs. 42.6%, respectively; hazard ratio 1.11; 95% confidence interval 0.775, 1.595; p = 0.566). DKP/TRAM achieved superiority over TRAM in total pain relief at 4, 6, and 8 h (p < 0.05). Conversely, in relation to the secondary endpoints, a significantly greater reduction in NRS-PI score was seen with DKP/TRAM versus placebo starting from 1 h, and this reduction remained numerically lower throughout 8 h. Summed pain intensity difference values were also significantly lower at 4, 6, and 8 h with DKP/TRAM compared to TRAM (p < 0.05). Overall, DKP/TRAM was well tolerated.

Although the primary endpoint was not met, secondary efficacy analyses suggest the superiority of DKP/TRAM over placebo and TRAM alone in terms of total pain relief. DKP/TRAM can be considered to be an effective and safe option for the treatment of moderate to severe acute LBP.

EudraCT number: 2019-003656-37; ClinicalTrials.gov Identifier: NCT05170841.