According to the outcomes from the phase 3 ACTIVE trial, the frontline treatment with the drug apatinib together with gefitinib has been shown superior progression-free survival (PFS) in patients with the advanced EGFR-mutant non-small cell lung cancer (NSCLC).
"This combined regimen of apatinib plus gefitinib is expected to be established a new first-line treatment option for patients with EGFR-mutant NSCLC,” words by Li Zhang, MD, of the Sun Yat-sen University Cancer Center in China, and who was the presenter of the study.
The ACTIVE trial was conducted by enrolling the total of 313 patients. The patients were assigned in order to receive apatinib plus gefitinib or placebo plus gefitinib.
The median age at baseline was 59 years and 41% of considered patients were the male. About three-quarters of patients were the nonsmokers and maximum had the stage IV disease. Epidermal Growth Factor Receptor ex19del existed in about 52% of patients.
The ORR (Objective Response Rate) was common between arms, at 77.1% & 73.7% combined regimen of apatinib plus gefitinib in comparison to the gefitinib, respectively (P =.5572). The duration of response, however, was longer in the apatinib plus gefitinib group at 12.9 months compared with 9.3 months in the gefitinib arm.
The combined regimen of the drugs apatinib plus gefitinib prolonged progression free survival with a median of about 13.7 months in comparison to about 10.2 months with gefitinib 250 mg. When stratified by the mutation, patients with the exon 19 deletion mutation had increased progression free survival (HR, 0.67; 95% CI, 0.45-0.99) vs patients with L858R mutation (HR, 0.72; 95% CI, 0.48-1.09).
The safety profile of a combined regimen of apatinib plus gefitinib was consistent with that of individual treatment components, with no additional safety signal identified. Rates of all-grade treatment-related adverse events (TRAEs) and grade ≥3 TRAEs were 98.7 % versus 98.1 % and 84.1 % versus 37.7 % for apatinib plus gefitinib vs placebo plus gefitinib, respectively.
Hypertension (46.5 % for apatinib plus gefitinib versus 2.6 % for placebo plus gefitinib), proteinuria (17.8 % versus 0.6 %) and alanine aminotransferase increase (7.6 % versus 3.2 %) were the most common grade ≥3 TRAEs.
With a conclusive statement, Dr Zhang stated that, “apatinib plus gefitinib is generally well tolerated, and the toxicities are manageable.” “This combined regimen is able to provide a bit more convenient treatment for those patients who needed long-term administration", He also added.
Background of Apatinib: Rivoceranib (Apatinib) specifically is the first successful small-molecule TKI (Tyrosine Kinase Inhibitor) in order to be approved for the treatment of gastric cancer (China, Dec 2014).
It is quite necessary to consider that in the US and other existing jurisdictions, this medicine is investigational and the safety as well as efficacy yet to be established. Orphan Drug designation has been granted in Europe, South Korea and the US.
It has been clinically tested with more than the 1K patients at the global level. Apatinib has also demonstrated potential in order to boost the results in combination treatment together with chemotherapeutics and immunotherapy, as well as for maintenance therapy.
Additional data as well as research will require to be conducted in order to verify the clinical applications in this context.
Background of Gefitinib: Gefitinib, also known by its brand name Iressa, is a kind of agent that is prescribed for certain breast, lung and other cancers.
Gefitinib falls under the class of drugs named EGFR inhibitor, which mainly interrupts the signaling with the help of EGFR in target cells.
Therefore, uses of gefitinib are only known to be quite effective in cancers with mutated and overactive EGFR, but resistances to this drug can arise with the help of other mutations. This medication is marketed by Teva and AstraZeneca.