Apatinib, an oral inhibitor of VEGFR-2, has been demonstrated rapid efficacy and safety in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients within the first 8 weeks in the previous study. Here we report the biochemical and structural response in progressive RR-DTC within 14 cycles' follow up.
Ten patients (5 female, 54±14 y) with RR-DTC who experienced PD during the previous 14 months received apatinib 750 mg qd in 28-day cycles until PD, drug intolerance or consent withdrawal from the study. Serum thyroglobulin/thyroglobulin-antibody (Tg/TgAb) and total target lesions (TL) examined by CT, MRI etc., were evaluated every follow-up. All adverse events (AE) were recorded and graded according to CTCAE 4.0. Study interruption and sequential reduction (500 and 250 mg qd) were allowed due to AE.
Serum Tg levels dropped rapidly in all patients on an average of 6 weeks with a median reduction of 70% (range 7%-91%), and a total of 18 TL decreased rapidly in the average of 9.2 weeks with an average 42% decline, indicating a rapid biochemical and structural response, then tended stable thereafter. Fluctuations in Tg could be observed in all subjects because of treatment interruption or dose regulation, rebounding by a median of 14% (range, 2-135%). The TLs seemed not to be affected by drug withdrawal that much as Tg. AE≥grade 3 occurred in all patients, most frequently including hand-foot-skin reaction (60%), hypertension (40%) and hypocalcemia (40%). At the end of the 14th cycle, 6 patients were still in follow-up evaluated as PR, with an average reduction of 53% in TL and median reduction of 78% (range, 9-88%) in Tg. Two experienced PD, whose PFS were 112 days and 281 days. The remaining 2 subjects dropped out because of proteinuria and dying of pneumonia.
In patients with progressive RR-DTC, the encouraging biochemical and structural response, median follow-up time, and tolerable AEs of apatinib have prompted further investigation in a phase 3 trial.
Clinical trial identification
Legal entity responsible for the study
National Natural Science Foundation of China (Grant No 81571714).
All authors have declared no conflicts of interest.