Catequentinib Shows Promise in Treatment of Advanced Synovial Sarcoma

Catequentinib (Anlotinib) improved disease control and progression-free survival (PFS) in patients with advanced synovial sarcoma (SS) compared with dacarbazine, according to data from the phase 3 APROMISS study (NCT03016819) presented during the 2021 ASCO Annual Meeting.¹

Results from a single arm of the trial showed that patients treated with catequentinib achieved a median PFS of 2.89 months (95% CI, 2.73-6.87) compared with 1.64 months (95% CI, 1.45-2.70) in those treated with dacarbazine (HR, 0.449; 95% CI, 0.270-0.744). More patients treated with catequentinib (n = 52) had PFS of at least 12 months at 29.6% vs 3.7% of patients treated with dacarbazine (n = 27).

“The difference in PFS was significant, and the risk of disease progression was reduced by 67%,” said Brian A. Van Tine, MD, PhD, lead study author and an associate professor of medicine at Washington University School of Medicine, Siteman Cancer Center, in St Louis, Missouri. “Catequentinib is effective for the treatment of patients with SS.”

Catequentinib is a multi-targeted receptor tyrosine kinase (RTK) inhibitor targeting VEGFR1-3, FGFR1-3, PDGFRβ, c-Kit and RET. The agent has previously demonstrated efficacy across several tumor types and is approved in China for the treatment of patients with non–small cell lung cancer based on results from the randomized phase 3 ALTER303 trial (NCT02388919) and for patients with soft tissue sarcoma based on results from the phase 2/3 ALTER0203 trial (NCT02449343).²

APROMISS enrolled adult patients with metastatic or recurrent advanced SS. Patients had an ECOG performance status of 1 or less, measurable lesions by RECIST 1.1, and progressed on at least 1 line of therapy that must have included an anthracycline-containing regimen. Prior pazopanib use was permitted. The study was an intention-to-treat analysis and the primary end point was PFS.

Patients were randomized 2:1 to receive either catequentinib or dacarbazine. Catequentinib was administered orally at a dose of 12 mg once daily, 2-weeks on and 1-week off in a 3-week cycle. Dacarbazine was given intravenously. Patients with disease progression while being treated with dacarbazine were allowed to cross over to catequentinib at the time of progression.

The median age of patients in the catequentinib arm was 42.0 years (range, 20-80) and 40.5 years (range, 20-73) in the dacarbazine arm. Nearly three-quarters of patients treated with catequentinib (73%) received more than 1 prior line of therapy compared with 65.4% in the dacarbazine cohort. The majority of patients in both groups were White, 81.5% and 82.7%, respectively.

PFS rates were also reported for patients at 4-, 6-, and 12-month intervals. Patients in the catequentinib arm had response rates of 48.1%, 42.3%, and 26.9%, respectively. Those in the dacarbazine arm had response rates of 14.9%, 11.1%, and 3.7%, respectively. Van Tine noted that there was a statistically significant difference between those receiving catequentinib and those receiving dacarbazine (P < .05).

“Of note, there were 3 partial responses to catequentinib on study and 6 patients who [did not experience progression] greater than 1 year. In comparison no patients [treated with] dacarbazine had a partial response and only 1 patient made it to 1 year [progression-free],” Van Tine said.

In an analysis of patients based on prior pazopanib 40 patients who did not have prior pazopanib and were treated with catequentinib had a median PFS of 2.79 months (95% CI, 1.58-6.97) compared with 1.64 months (95 % CI, 1.45-1.78) in the 21 patients who went on to receive dacarbazine (HR, 0.347; 95% CI, 0.189-0.639; log-rank P = 0.0004). In those who were treated with prior pazopanib and went on to receive catequentinib (n = 12) the median PFS was 3.02 (95% CI, 1.55-not evaluable [NE]) compared with 2.14 months (95% CI, 1.28-NE) in 6 patients treated with dacarbazine (HR, 0.826; 95% CI, 0.266-2.566; log-rank P = 0.7683). Van Tine highlighted that those who received dacarbazine and had prior pazopanib saw an improved PFS compared with those who did not.

Finally, an observed benefit was observed with catequentinib across all subgroups.

In terms of safety, 23.1% of patients in the catequentinib group had an adverse effect (AE) of grade 3 or higher compared with 25.9% of those treated with dacarbazine. Notable grade 3 or greater AEs in the catequentinib cohort included diarrhea (5.8%) and hypertension (3.8%). In the 21 patients who crossed over from dacarbazine to catequentinib grade 3 or higher pneumothorax (4.8%) and hypertension (4.8%) were AEs of note.

“Catequentinib was well tolerated,” concluded Van Tine. “The most common AEs observed in the catequentinib group were hypertension, increased TSH, hypertriglycefidemia, diarrhea, and hand-foot syndrome.”

References

1. Van Tine BA, Chawla SP, Trent JC, et al. A phase III study (APROMISS) of AL3818 (Catequentinib, Anlotinib) hydrochloride monotherapy in subjects with metastatic or advanced synovial sarcoma. J Clin Oncol. 2021;39(suppl 15):11505. doi:10.1200/JCO.2021.39.15_suppl.11505
2. Gao Y, Liu P, Shi R. Anlotinib as a molecular targeted therapy for tumors. Oncol Lett. 2020;20(2):1001-1014. doi:10.3892/ol.2020.11685