The experimental combination of tremelimumab, durvalumab, and stereotactic body radiotherapy lack overall surival benefit in anaplastic thryoid cancer, phase 1 findings show.
Tremelimumab and durvalumab (Imfinzi) with stereotactic body radiotherapy (SBRT) did not improve overall survival (OS) for anaplastic thyroid cancer (ATC), according to findings from a pilot study (NCT03122496).1
With the poor prognosis left for patients with metastatic ATC, this pilot study aimed to examine the combination of tremelimumab and durvalumab along with SBRT in this patient population to evaluate its impact on improvement in OS.
A total of 13 patients were enrolled in the study, but only 12 participated in the trial as 1 became ineligible for the study due to continued decline in performance status. Those enrolled were aged 18 years and older with a histopathologic confirmation of ATC, an ECOG performance status of 0-2, and adequate normal organ and marrow function.2
Of those enrolled, 6 patients were male, had a median age of 71 years (range, 49–82), and an ECOG performance status of 1. There were 9 patients who had prior neck radiation and 9 who also had received prior chemotherapy. In the 9 patients where tissue was available, next-generation sequencing and PD-L1 staining were done.
Patients received up to 4 doses of tremelimumab at 75 mg given every 4 weeks as well as up to 1 year of durvalumab at 1500 mg given every 4 weeks. SBRT delivered to 1 metastatic site per standard of care using a standard 9Gy x 3 fractions was also given within 2 weeks after the completion of the first cycle of durvalumab and tremelimumab. After receiving 4 cycles of durvalumab in addition to tremelimumab, patients continued with single agent durvalumab every 4 weeks until disease progression, unacceptable toxicity, or a total of 12 months from date of initial treatment.
The primary end point of the trial was to evaluate OS in a time frame of 1 year for the combination of durvalumab, tremelimumab, and SBRT in patients with metastatic ATC.
Of the 12 patients who participated in the trial, high microsatellite instability (MSI) corresponding to mismatch repair defect was observed in 2 patients and a BRAF V600E mutation was seen in 3 subjects. There were no confirmed responses and only 1 patient had stable disease. This patient was treated with 4 or more cycles of the study drugs.
Additionally, the median time that patients were under treatment was 11 weeks (1–28 weeks), and MSI status did not seem to affect treatment response. High MSI patients were on treatment for 8–14 weeks before disease progression.
The median OS reported in patients was 14.5 weeks with 1 patient still alive beyond 1 year. Investigators noted that having a BRAF or p53 mutation did not seem to affect treatment outcome.