Lenvatinib/Pembro Combo for Advanced Anaplastic Thyroid Cancer

Haugen added that interest in the lenvatinib/pembrolizumab combination is high, and additional trials are supposedly being prepared at MD Anderson and Memorial Sloan Kettering cancer.
Outcomes of Small Study of Rare Cancer With Poor Prognosis

” As a field we should be passionate about these information and the innovative method to treating such innovative thyroid cancers,” she told Medscape Medical News.

” Our results indicate that a combination of lenvatinib and pembrolizumab is safe and efficient in clients with anaplastic thyroid cancer and induces high action rates including long-lasting remissions,” stated the authors when providing the findings at the virtual 90th American Thyroid Association (ATA) Annual Meeting.
The new results with the nonchemotherapy mix are motivating, commented welcomed discussant Melissa G. Lechner, MD, PhD, assistant teacher of medicine in the Onco-Endocrinology Program at the UCLA Jonsson Comprehensive Cancer.

” This is a fantastic first start utilizing FDA-approved agents and provides a structure for future studies,” she added. Nevertheless, she recommended that lenvatinib may not be the optimum targeted treatment to couple with immunotherapy and there might be other representatives that would do more to increase antigen expression and immunogenicity.
Talking about the new outcomes during another session at the conference, Bryan Haugen, MD, a professor of medicine and pathology at the University of Colorado School of Medicine, in Aurora, was also impressed with the findings.
” Some of these patients with anaplastic thyroid cancer have a tremendous response with a long-term effect, and some are complete responses … so this is actually encouraging,” he stated.

In clients with metastatic anaplastic thyroid cancer who have actually advanced on chemotherapy — who have a poor prognosis– a new combination of nonchemotherapy drugs reveals guarantee.
The mix of the multikinase inhibitor lenvatinib with the immunotherapy pembrolizumab has actually revealed long lasting actions and encouraging survival rates in a small scientific trial.

Dr Christine Dierks

In addition, the outcomes for the general study population showed a rate of steady illness at 3 months of 57.6% (15 of 26 patients) and a progressive illness rate of just 3.8% (one client).

Even with multimodal treatment of growth resection, chemotherapy, and irradiation, median total survival rates are just 3 to 5 months.

The overall action rate (ORR) was 38.5%, and 10 of 26 clients had a partial response.

Clients received lenvatinib, started at 20 mg/day, and pembrolizumab 200 mg administered intravenously every 3 weeks for as much as 2 years.

A further interim analysis of the very first 16 clients with anaplastic thyroid cancer to have a 2-year follow-up revealed remarkably high best ORR of 68.8%, and 11 of the 16 patients had a partial response.

Median progression-free survival in the 16 patients followed out to 2 years was 10 months and typical total survival was 11 months, with 25% of clients enduring more than 2 years (4 of 16), and the clinical benefit rate was 100%. Dierks said that the findings were impressive as in previous research studies “the best progression-free survival seen up until now is 5.4 months for carboplatin/taxol.”

Even with these risks of unfavorable occasions, the extremely motivating ORR and other results “clearly show that … this therapy is helpful, and with preventive procedures the outcome should improve,” Dierks said.

Haugen stated this is essential. “This field is continuing to move on to much better understand who can take advantage of these treatments,” he stated.

Grade 3 and 4 toxicities took place in 19 of 36 clients (53%), including hemorrhage after the development of fistula (11%), sepsis (8.3%), pneumonia (2.7%), aspergillus pneumonia (11%), autoimmune liver disease (5.6%), pulmonary embolism (5.6%), and other apoplexy (8.3%).

Response Rates, PFS Higher Than Other Treatments
Dierks commented that the response rates were notably higher than those observed with other treatments.

Recently, progress has been made with targeted agents. For the 25% or so of clients with BRAF V600E altered tumors, high response rates have actually been seen with BRAF/MEK inhibitor combinations.

She reported arise from the stage 2 ATLEP trial. All of the 26 patients with anaplastic thyroid cancers had phase IVB disease and had been pretreated mainly with chemotherapy/radiotherapy and surgical treatment, however none had the BRAF V600E anomaly.

As a preventative measure, all clients are now offered prophylactic treatment with amphotericin B and Cotrim Forte to avoid fungal infections and specific pneumonia, she stated. Because starting these prophylactic treatments, “no further systemic fungal infections occurred.”.

” The best general action rates for other systemic treatments like doxorubicin monotherapy or carboplatin/taxol are 10% to 25% … far listed below the 68% we see with the lenvatinib/pembrolizumab mix” at 2-year follow-up, she informed Medscape Medical News.

Autoimmune hepatitis is a known complication of the immune checkpoint inhibitor pembrolizumab.

There may also be a method of identifying clients most likely to take advantage of the mix, she noted. In an earlier analysis of their very first 8 clients, released in July in Thyroid, the authors determined that tumors with particular attributes were more than likely to react to treatment.

Dierks has actually reported being on advisory boards for Eisai, Novartis, Bristol Myers Squibb, and Lilly. Lechner has actually reported no pertinent monetary relationships.

She noted that most of the major negative events, including fistula, bleeding, and pulmonary embolism, were reported in the lenvatinib monotherapy trial and are known problems of the treatment.

Presenting author Christine Dierks, MD, of the University of Halle, Germany, stated that anaplastic thyroid cancer only represents about 2% of all thyroid cancers however has a distinctively bad prognosis, accounting for up to 50% of thyroid cancer deaths.

The fungal infection observed in the research study was unexpected, however likely arised from the mix of cervical irradiation, high-dose steroids for longer durations, and the decreased healing process caused by lenvatinib, Dierks said.

However for the staying 75% of patients with anaplastic thyroid cancer without identified anomalies, action rates to any drug therapy are low– in the region of 10% -20%, Dierks noted.

90th ATA Annual Meeting. Abstract # 4. Provided September 30, 2021.

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