Data presented during the 2022 ESMO Congress showed lenvatinib plus pembrolizumab to elicit an objective response rate of 34.3% after 3 months in evaluable patients, meeting the primary end point of the phase 2 ATLEP trial.
Lenvatinib (Lenvima) combined with pembrolizumab (Keytruda) induced high response rates, and showed acceptable safety in patients with metastasized anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid carcinoma (PDTC), according to final data from the phase 2 ATLEP trial (NCT02973997).1
Data presented during the 2022 ESMO Congress showed that the combination elicited an objective response rate (ORR) of 34.3% after 3 months in evaluable patients (n = 12/35), meeting the primary end point of the trial. Among those who responded, 34.3% achieved a partial response (PR), 60% had stable disease (SD), and 5.6% experienced disease progression.
In the 27 patients with ATC, the ORR achieved with lenvatinib plus pembrolizumab was 51.9% (n = 14), with a best overall response (BOR) of a PR within 2 years in 51.9% of patients and SD in 48.1% of patients. In this group, the clinical benefit rate (CBR) with the regimen was 100%.
Among the 8 patients with PDTC, the doublet induced an ORR of 75% (n = 6), with a BOR of a PR within 2 years in 75% of patients and SD in 25% of patients. In these patients, the CBR achieved with the regimen was also 100%.
“The lenvatinib/pembrolizumab combination is effective in [patients with] ATC and PDTC,” lead study author Christine Dierks, MD, of the University of Halle-Wittenberg, Germany, said in a presentation of the data. “The primary end point was reached. Lenvatinib/pembrolizumab improves ORR, CBR, median progression-free survival [PFS], and overall survival [OS] in [those with] ATC compared with historical controls, and 25% have long-term responses [of] over 2 years.”
Seventy-five percent of patients with ATC or PDTC do not harbor targetable mutations or fusions, according to Dierks, who added that chemotherapy is an effective option for 10% to 20% of this population. It has been shown that multimodal approaches can extend survival to 4 to 5 months in those with ATC. Additionally, findings from a retrospective study have indicated that in PD-L1–positive patients, the combination of lenvatinib and pembrolizumab produced a response rate of 75%.2
The phase 2 prospective ATLEP trial enrolled 35 patients with ATC and PDTC who had blood pressure up to 160/90 mmHg and who did not previously receive lenvatinib for more than 10 days or previous immune checkpoint inhibition. Those whose tumors harbored BRAF V600E mutations were excluded from the study.
Lenvatinib was examined at 3 dose levels—20 mg (dose level 0), 14 mg (dose level -1), and 10 mg (dose level -2)—and paired with pembrolizumab, which was given at a dose of 200 mg as part of 21-day treatment cycles. Treatment was continued until progressive disease per immune-related RESPONSE criteria.
ORR at 3 months served as the primary end point for the research, and secondary end points comprised PFS, disease control rate, BOR, OS, and safety.
The median age of participants at the start of treatment was 64 years (range, 39-82), and 60% were men. Moreover, 17.1% of patients had an ECOG performance status of 0, 65.7% had a status of 1, and 17.1% had a status of 2. Of those enrolled to the trial, 77.1% had ATC and 22.9% had PDTC. Most patients had stage IVC, or metastasized, disease at the start of treatment (97.1%) and the remainder had stage IVB disease (2.9%). Regarding prior treatment, 97.1% underwent surgery, 80% had cervical radiation therapy, 80% had chemotherapy, and 20.6% had radioiodine therapy.
“If you look at the waterfall plot, you can see that [among] patients [who] responded to the treatment, the [patients with] PDTC responded better than the [patients with ATC,” Dierks noted.
Additional data showed that the median PFS in those with ATC was 10 months with lenvatinib plus pembrolizumab, with a 12-month PFS rate of 41.2%. The median OS in these patients was 11 months, with a 12-month OS rate of 44%. Notably, 25% of patients were noted to have remissions that lasted for longer than 20 months.
In those with PDTC, the median PFS with the doublet was over 20 months, with a 12-month PFS rate of 75%. The median OS in these patients was not yet reached, and the 12-month OS rate was 75%.
In terms of safety, the most frequent toxicities experienced with the combination were hypertension (71.4%), mucositis (74.2%), and hand-foot syndrome (45.7%), “which are known to be associated with lenvatinib,” Dierks noted.
Specifically, in those with ATCs, fistula development was observed in 11% of patients and arterial hemorrhage in 11%. “It was very unexpected, but we also had 11% of patients with Aspergillus pneumonia, which led us to prophylactic treatment for patients with antifungal [agents] and cotrim and aciclovir,” Dierks explained.
Unlike what had been observed in earlier findings, the current data do not demonstrate a correlation between PD-L1 status with OS and PFS, Dierks added. Subanalyses are being done, as well as RNA sequencing and whole-exome sequencing, to identify other biomarkers that may be better for this patient population, she concluded.