Pralsetinib achieves tissue-agnostic benefits for patients with RET gene fusions (Mutation in lung, thyroid, & other cancers)

Medical Xpress / University of Texas M. D. Anderson Cancer Center / Nature Medicine ^ | August 12, 2022 | Subbiah, V. et al

[ConservativeMind]

The highly selective RET inhibitor pralsetinib was well-tolerated and demonstrated robust, durable responses in patients with RET fusion-positive cancers regardless of tumor type.

The study results showed an overall response rate of 57% and a disease control rate of 83% in patients with a range of cancer types. These findings build upon positive results previously reported in RET-altered non-small cell lung cancer (NSCLC) and thyroid cancer, suggesting the targeted therapy may offer tissue-agnostic benefits to patients with RET fusions.

"We've had an explosion in clinical next-generation sequencing that allows us to understand shared biomarkers across multiple tumor types, and this study was important to determine if RET fusions are actionable across cancer types," said Vivek Subbiah, M.D. "We observed responses regardless of tumor type, prior therapy or gene fusion partner. These data validate RET as a tissue-agnostic target with sensitivity to RET inhibition."

RET fusions occur when a piece of the chromosome containing the RET gene is broken and rejoined with another chromosome, creating a fusion protein that fuels the cancer. RET alterations are most common in medullary thyroid cancers, papillary thyroid cancers and NSCLC, but they occur infrequently in many other tissue types.

To determine if the therapy provided benefit beyond NSCLC and thyroid cancers, the open-label, single-arm study also enrolled patients with diverse RET fusion-positive solid tumors. Common cancers in this cohort included pancreatic cancer, cholangiocarcinoma, neuroendocrine tumors and sarcoma.

The study enrolled 29 patients with 12 different cancer types. Most patients had metastatic disease (87%) and received prior therapies for their cancer (87%).

Of these, 13% had a confirmed complete response and 43% had a confirmed partial response.

"Although RET fusions are extremely rare beyond lung and thyroid cancers, these patients need effective therapies," Subbiah said. "These findings demonstrate the potential to benefit patients across tumor types.

[ConservativeMind]

87% had metastatic disease and 13% had complete remission, in not necessarily exclusive populations.

[ConservativeMind]

The “Take Charge Of Your Health” Ping List
This high volume ping list is for health articles and studies which describe something you or your doctor, when informed, may be able to immediately implement for your benefit.

Email me to get on either the “Common/Top Issues” (20% fewer pings) or “Everything” list.

[ifinnegan]

Tissue -agnostic is a weird term. Tissue-independent seems better.

It’s a ret antagonist so cancers driven by the ret fusion oncogenes product will be inhibited independent of the cancer type.

[Olog-hai]

Does the Pralsetinib Liberation Organization approve . . . ?