medwireNews: The phase III DREAM trial indicates that an oral formulation of paclitaxel is noninferior to the intravenous (iv) preparation with regard to progression-free survival (PFS) and is tolerable in patients with advanced gastric cancer who have failed first-line therapy.
The researchers explain that paclitaxel is currently only available as an iv formulation, and owing to its poor solubility in water, has to be given with a vehicle to aid administration. However, the most commonly used vehicle “is associated with hypersensitivity reactions and altered/nonlinear pharmacokinetics of paclitaxel”, they say.
Furthermore, “[t]he oral administration route is preferred to the IV route for paclitaxel, not only for convenience but also because achieving a longer exposure is more important than a higher concentration for the efficacy of cell-cycle phase-specific agents such as paclitaxel”, the study authors write in Annals of Oncology.
Therefore, they recruited 236 patients who had not responded to first-line chemotherapy with a fluoropyrimidine, given alone or alongside platinum-based agents, to investigate the efficacy and tolerability of DHP107, an oral preparation comprising paclitaxel and lipids.
In the per-protocol set, progression-free survival (PFS) was a median of 3.0 months for the 106 participants who were randomly assigned to receive DHP107 200 mg/m2 twice daily on days 1, 8 and 15 of every 4-week cycle and 2.6 months for their 116 counterparts given iv paclitaxel 175 mg/m2 on the first day of each 3-week cycle. This equated to a nonsignificant hazard ratio of 0.85, where the upper limit of the confidence interval was within the prespecified noninferiority margin.
Other efficacy endpoints, such as median overall survival and overall response rate – which were both assessed in the final analysis set comprising all 236 participants – also did not differ significantly between the DHP107 and iv paclitaxel groups, at 9.7 versus 8.9 months and 17.8% versus 25.4%, respectively.
Grade 3–4 adverse effects occurred in 68.6% of DHP107-treated patients, compared with 83.9% of those given iv paclitaxel. Neutropenia was the most common side effect in both study arms, with events of grade 3 or 4 observed in 42.4% and 53.4% of participants, respectively.
Yoon-Koo Kang, from the University of Ulsan College of Medicine in Seoul, South Korea, and fellow DREAM investigators point out that there were no hypersensitivity reactions in the DHP107 group even
though the agent was given without premedication. By contrast, 2.5% of iv paclitaxel-treated patients had hypersensitivity reactions despite receiving routine premedication with dexamethasone, diphenhydramine and H2-blocker.
And they conclude: “DHP107 is the first oral paclitaxel formulation to demonstrate equivalent efficacy and safety to IV paclitaxel for the treatment of advanced gastric cancer.
“This novel oral formulation of paclitaxel may also prove useful in other tumor types where IV paclitaxel is currently used (e.g. breast cancer).”
Kang Y-K, Ryu M-H, Park SH, et al. Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus IV paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy. Ann Oncol; Advance online publication 9 February 2018. doi: https://doi.org/10.1093/annonc/mdy055
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