Apatinib a new treatment alternative for thyroid cancer?

In individuals with progressive locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC), the VEGFR-2* inhibitor apatinib demonstrated significant clinical benefits in terms of progression-free survival (PFS) and overall survival (OS), with a manageable safety profile, findings from the phase III REALITY trial suggest.

About a third of patients with DTC experience recurrence and 30 percent of tumours eventually become refractory to RAI therapy. [J Cancer 2011;2:193-199; Am J Med 1994;97:418-428] Despite the reported PFS benefit of other angiogenesis inhibitors such as sorafenib and lenvatinib for RAIR-DTC, no significant OS benefit has been observed, apart from that seen in a subgroup of patients >65 years. [Lancet 2014;384:319-328; N Engl J Med 2015;372:1868; J Clin Oncol 2017;35:2692-2699]

Given the poor prognosis (10-year survival rate of 10 percent) and limited treatment options, exploration of alternative treatment strategies for this patient subgroup is warranted, said the researchers. [J Clin Endocrinol Metab 2006;91:2892-2899; J Clin Endocrinol Metab 2013;98:172-180] “[Our findings] showed that patients with progressive locally advanced or metastatic RAIR-DTC could derive clinical benefits from apatinib.”

Ninety-two participants from China (61 percent female, mean age at baseline 55.7 years) were randomized 1:1 to receive apatinib 500 mg daily or placebo. Placebo recipients who had disease progression were allowed to cross over to apatinib. [JAMA Oncol 2021;doi:10.1001/jamaoncol.2021.6268]

After a median follow-up of 18.1 months, median PFS was significantly longer with apatinib compared with placebo (22.2 vs 4.5 months; hazard ratio [HR], 0.26; p<0.001). PFS rates were also higher with apatinib vs placebo at both 12 (60 percent vs 12 percent) and 24 months (37 percent vs 4 percent). “REALITY met its primary endpoint of PFS at the prespecified interim analysis,” said the researchers.

In the full analysis set, apatinib increased median OS compared with placebo (not reached vs 29.9 months; HR, 0.42; p=0.04). “[The] improved OS could potentially be underestimated owing to patients with progressive disease in the placebo arm crossing over to apatinib therapy,” the researchers explained.

The apatinib arm also had markedly higher confirmed objective response rate (ORR) and disease control rate (DCR) as opposed to placebo (54 percent vs 2 percent [ORR] and 96 percent vs 59 percent [DCR]; p<0.001 for both).

About three-quarters (74 percent) of apatinib recipients reported grade ≥3 treatment-related adverse events (TRAEs), the most common being hypertension (35 percent) and hand-foot syndrome (17 percent); none of these occurred among placebo recipients. Thirty-seven percent of those on apatinib had a dose reduction due to TRAEs of any grade.

“The safety profile of apatinib was consistent with the AEs associated with other antiangiogenic therapies, including the most common [AEs],” said the researchers. [JAMA Oncol 2016;2:529-534; Oncologist 2018;23:306-315; Semin Oncol 2019;46:57-64]

However, the findings may not be generalizable across all populations, as these were obtained from a Chinese cohort. The use of placebo as control owing to limited drug accessibility may have also been a limiting factor, especially since patients on placebo were permitted to transition to apatinib following disease progression.

“[Nonetheless,] this study suggests that apatinib offers a favourable benefit-risk profile in patients with RAIR-DTC,” said the researchers.