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Multimodal therapies almost double survival in anaplastic thyroid cancer


 

REPORTING FROM ATA 2019

Overall survival for patients with anaplastic thyroid cancer was boosted when their care facilitated a rapid work-up, comprehensive treatment planning, and integrated implementation of multimodal therapies.

Median survival for participants in a specialized program who have been able to benefit from targeted therapy and immunotherapy now stands at 16 months, with 43% of patients surviving 2 years or more, said Anastasios Maniakas, MD, at the annual meeting of the American Thyroid Association.

Median survival was 8 months during 2000-2013, before the program, dubbed FAST (Facilitating Anaplastic Thyroid Cancer Specialized Treatment), was initiated at the University of Texas MD Anderson Cancer Center, Houston.

These increased survival rates were driven primarily by better targeting of mutation-specific therapy and by immunotherapy, said Dr. Maniakas, a fellow in head and neck surgery at the center. This targeting, in turn, was facilitated by timely staging and genetic work-up, as well as appropriate clinical trial enrollment.

As word has spread about the program, referrals went up by 44%, said Dr. Maniakas. Members of the FAST team include representatives from oncologic endocrinology, head and neck surgery, radiation oncology, pathology, and basic science.

Historically, anaplastic thyroid cancer (ATC) has had a 12-month overall survival rate of less than 30% for patients who have advanced disease, said Dr. Maniakas, citing a recent analysis showing that, in 1,567 ATC cases, the median survival was just 4 months, and the 6-month survival rate was 35%.

The FAST team’s engagement starts with rapid intake whereby patients see a physician within 3-5 days of initial contact with the center, explained Dr. Maniakas. A prescheduled work-up is completed within another 3-7 days. It includes basic lab work, cell-free DNA testing, BRAF immunohistochemistry, and molecular testing. Additional consults and appropriate medical imaging for staging are also included in the initial work-up.

With these data in hand, physicians meet again with patients in a treatment-planning clinic to assess eligibility for participation in a clinical trial. Patients will otherwise receive standard-of-care therapy that may include surgery or BRAF-directed therapy. However, said Dr. Maniakas, the FAST approach has resulted in a boost of more than 30% in clinical trial participation by ATC patients. Adjunctive therapies are also tailored to patients under the care of the FAST team, which may include stereotactic body-radiation therapy, surgery, and immunotherapy.

The team is tracking a cohort of patients who received surgery with or without radiation therapy, preceded by neoadjuvant BRAF/MEK inhibitor therapy – an approach used since 2017. Of 20 patients who were positive for BRAF-V600E, 16 are still alive at a median 1.21 years of follow-up since diagnosis, said Dr. Maniakas. The median survival time for those who did not receive surgery is 0.8 years, whereas the median survival has not been reached for those who also had surgery.

Molecular testing and initial screening of ATC patients is an essential component of the cancer center’s precision medicine approach, said Dr. Maniakas. “Genetic profiling has become a key player in ATC management and survival.”

In looking at outcomes at the cancer center, Dr. Maniakas and his collaborators divided the patients into three groups. The first included 227 patients seen during 2000-2013, before the program was initiated. The 100 participants in the second group initiated treatment sometime during 2014-2016, after the program was launched but before the targeted therapy and immunotherapy trial was fully implemented. Since 2017, 152 participants in the third group have had the opportunity to participate in the clinical trial, as well as receiving surgery with or without radiation therapy after neoadjuvant immunotherapy.

Since 2017, 97% of ATC patients have had genetic profiling done. Most patients are receiving rapid determination of BRAF-V600E status with immunohistochemistry, with results available in a few days, followed by liquid biopsy (available in about 2 weeks), and then next-generation sequencing. Results for the latter, considered the gold standard, can take up to 3 weeks.

Patients participating in the program were aged a mean 65 years at diagnosis, and just over half were men. The number of patients receiving targeted therapy has continued to rise, said Dr. Maniakas. From 2000 to 2013, just 9% of patients received targeted therapy; from 2014 to 2016, that figure rose to 43%; and since 2017, 61% of patients have received targeted therapy (P less than .001).

“Landmark changes in the management of ATC patients as a whole have had a direct impact to the significant increase in overall survival,” said Dr. Maniakas.

He added that the cancer center’s experience could inform future ATC guidelines. Patients with this deadliest of thyroid cancers should all have rapid molecular testing, followed by timely, targeted therapy. Clinical trial eligibility should be considered for all patients. Finally, guideline authors should take note of the ongoing favorable survival rates seen for patients receiving surgery after neoadjuvant therapy.

Dr. Maniakas reported no outside sources of funding and that he had no relevant disclosures.

SOURCE: Maniakas A et al. ATA 2019, Short Call Oral Abstract 9.

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