Brian A. Van Tine, MD, PhD, discusses the study design, key findings, adverse events, and research beyond the APROMISS study.
Catequentinib (Anlotinib) significantly prolonged progression-free survival (PFS) in patients with synovial sarcoma who experienced disease progression following anthracycline-containing therapies, according to Brian A. Van Tine, MD, PhD, who added that the agent represents a potentially safer option than existing therapies available to this population.
Results from the phase 3 APROMISS study (NCT03016819), which were presented during the 2021 ASCO Annual Meeting, showed that catequentinib (n = 52) resulted in a median PFS of 2.89 months (95% CI, 2.73-6.87) compared with 1.64 months (95% CI, 1.45-2.70) with dacarbazine (n = 27; HR, 0.449; 95% CI, 0.270-0.744; P = .0015).
In the investigative arm, the 4-, 6-, and 12-month PFS rates were 48.1%, 42.3%, and 26.9%, respectively; these rates were 14.9%, 11.1%, and 3.7%, respectively, in the control arm. Notably, prior treatment with pazopanib (Votrient), the only FDA-approved TKI currently available for this population, did not impact the PFS benefit achieved with catequentinib.
“We have a second TKI that will hopefully be FDA approved, so we can then go from one to the other. If [a patient doesn't] tolerate one [agent], we [now] have a backup,” Van Tine said. “[This is] always good, because especially when [these agents are] tolerated well, [they will provide] some patients [with] prolonged stability which…really helps quality of life.”
In an interview with OncLive®, Van Tine, lead study author and an associate professor of medicine at Washington University School of Medicine, Siteman Cancer Center, in St Louis, Missouri, discusses the study design, key findings, adverse events, and research beyond the APROMISS study.
Van Tine: AL3818, internationally known as anlotinib, but now known in the United States as catequentinib, is a multi-targeted TKI. Pazopanib, which is FDA approved for the treatment of sarcoma, is available for the treatment of all soft tissue sarcomas outside of liposarcoma; however, it’s the only oral TKI used in the entire field, and there's room to have more than 1.
Interestingly, an ongoing 3-arm, phase 3 clinical trial is looking at leiomyosarcoma and alveolar soft part sarcomas and synovial sarcoma; these are individual subtypes of soft tissue sarcoma, [and we have seen] good evidence that tyrosine kinase inhibition is active. [At the 2021 ASCO Annual Meeting, we presented] just the [data from the] synovial sarcoma arm because it matured first. What we saw is that there is a role for tyrosine kinase inhibition with not only pazopanib, but now catequentinib, within this space.
[APROMISS] is a randomized phase 3 clinical trial with 3 arms. Within the synovial sarcoma arm, patients were either randomized to receive catequentinib or dacarbazine. At the time of progression on dacarbazine, patients went on to receive catequentinib. Therefore, overall survival is not an outcome measure of this trial, but progression-free survival [PFS] is. We looked at quality of life, safety, and efficacy within this clinical trial.
The key highlights are that we were able to pull off a phase 3 randomized trial with [only] [patients with] synovial sarcoma, which is a subtype of soft tissue sarcoma that represents less than 10% [of all patients with sarcoma]. We were only looking at [those with] advanced synovial sarcoma [who had] metastatic disease and who had [previously been treated with an] anthracycline—that's a very low number of patients.
We found that there was a PFS benefit in patients [who received] catequentinib over dacarbazine. More importantly, we found that prior pazopanib use didn't affect outcomes. As such, just like with the treatment of gastrointestinal stromal tumor, this would suggest that not only can you go from one KIT inhibitor to another, [but] within synovial sarcoma, we may now be able to [do] multiple attempts [with] a TKI for the treatment of this rare disease.
Most sarcoma doctors are well aware of the safety profile of pazopanib and the [effects] we are used to managing. What we've found in terms of grade 3 or higher adverse effects, is that they may be relatively fewer [with catequentinib]. Other than the expected diarrhea and hypertension, we're not [observing] the same amount of acute liver failure [that we have seen with pazopanib]. Overall, in my opinion, it's a better tolerated drug.
Hopefully by next year, we look forward to presenting [data from] the alveolar soft part [sarcoma], single-arm portion of this trial; that part is not randomized due to the ultra-rarity of the disease. Also, [we want to see data from] the leiomyosarcoma arm, which is another randomized [arm], where [patients are] randomized to placebo [or catequentinib]. If that also turns out to be positive, I look forward to seeing Advenchen and their partner companies developing this as they have in China across the rest of soft tissue sarcoma.
[Researchers could also] potentially look at combination therapies, which were not done in the same way with pazopanib at the time [the agent] was available. This may allow us to look at adding [agents] to catequentinib for higher efficacy, more prolonged durability, and potentially a greater response rate.
I was very excited to see the beginning of the SPEARHEAD-1 trial [NCT04044768] read out; [those data were] positive. [Another] trial that is really interesting is the work [that is being done by] Matthew A. Ingham, MD, of Columbia University Herbert Irving Comprehensive Cancer Center, [and colleagues, which is] looking at PARP inhibitors in the uterine leiomyosarcoma.