Thyroid cancer treatment does not benefit from immune modulators

According to the findings of a multicenter phase II clinical trial, treating people who have differentiated thyroid cancer (DTC), an advanced form of thyroid cancer that arises from thyroid follicular cells, with the targeted tyrosine kinase inhibitor (TKI) cediranib in addition to their treatment with the TKI cediranib did not help their prognosis.

The results were released in Annals of Oncology.

The majority of DTC patients benefit from effective treatment. However, a tiny percentage of cancer patients experience recurrence or metastases to unrelated organs, making it difficult to manage with standard treatments such as surgery, hormone therapy, chemotherapy, and radioactive iodine (RAI) therapy.

In recent years, there has been an increased interest in treating these patients with TKIs that target vascular endothelial growth factor receptor (VEGFR) signalling in the tumour microenvironment. These potent angiogenesis mediators target the formation of new blood cells, a process that plays an important role in the progression of thyroid cancer.

Oncologists Ari Rosenberg, MD, and Everett Vokes, MD, of UChicago Medicine, set out to evaluate the efficacy and safety of cediranib, a TKI that targets many VEGFRs. Additionally, the researchers proposed that pairing the medication with the immunomodulatory medicine lenalidomide would provide this group of patients with extra benefits. Early clinical trials suggested that this medication displays a similar effect against DTC. It is also known to disrupt angiogenesis and have anti-tumour activities in other malignancies. In many cancer diseases, recent combination therapies combining conventional medicines and immunotherapies have produced greater results.

“With this scope, we set out to evaluate whether immunomodulation by lenalidomide in combination with cediranib would improve disease-free survival over cediranib alone,” said Rosenberg, Assistant Professor in the Section of Hematology and Oncology at the UChicago Medicine Comprehensive Cancer Center.

108 participants were enrolled from various institutions in the United States and Canada in phase II clinical research. They were randomised to one of the two therapy groups, with 69 patients receiving cediranib plus lenalidomide and 39 patients receiving cediranib alone. According to the objective response rate (ORR), the cediranib alone group's median progression-free survival (PFS) was 14.8 months, and 44 per cent of patients had tumours that had completely or partially disappeared. Surprisingly, treatment with cediranib alone did not prove to be any more effective than treatment with lenalidomide added.

“There are many recent examples in the literature demonstrating the combination of VEGF-targeted TKIs and immunotherapeutic strategies can be very effective, both preclinically and clinically, in multiple cancer conditions, like renal cell carcinoma and hepatocellular carcinoma,” Rosenberg said. “And yet, this strategy does not appear to work in this particular disease with lenalidomide.”

The results of the data's final analysis showed that cediranib is an active agent, meaning that its ORR and PFS are comparable to those of other approved VEGFR-targeted tyrosine kinase inhibitors available on the DTC market, such as lenvatinib, sorafenib, and vandetanib.

Rosenberg said that because single-arm studies often provide false-positive outcomes and because immunomodulation has so far failed to treat thyroid cancer, this study emphasises the value of randomised trial design.

“The most important point of this study is that the addition of lenalidomide, an immunomodulatory agent, didn’t improve the progression-free survival over cediranib alone, despite what appeared to be promising single-agent activity in DTC, and should not be combined with VEGFR-targeted TKIs,” said Rosenberg.

“Despite the advances in the field since the time of conceptualization and the enrollment of patients from 2010-2015, the implications remain quite relevant as outcomes beyond single VEGFR-targeted TKIs in DTC have not improved,” Rosenberg added.

“Our study results highlight an unmet need with the current strategies of harnessing the body's immune system to treat thyroid cancer and the need to evaluate new combinations and new mechanisms, in particular new immunotherapeutic strategies that may be more effective than immunomodulatory strategies or immune checkpoint inhibitors alone,” he said.