Pembrolizumab Boosts Survival in Anaplastic Thyroid Cancer

Editor’s note: This story has been revised to include additional comments. 
CHICAGO — In patients with stage IVB anaplastic thyroid cancer, the inclusion of adjuvant pembrolizumab to conventional multimodal therapy shows significant benefits in reducing the recurrence risk and improving survival in the rare, aggressive cancer.
“The data are quite compelling at this point,” first author Maria E. Cabanillas, MD, of the University of Texas MD Anderson Cancer Center, in Houston, Texas, told Medscape Medical News. “We have already adopted the strategy of a checkpoint inhibitor [pembrolizumab] after chemoradiation for stage IVB anaplastic thyroid cancer at MD Anderson, and we feel that others should too,” she said.
The study was presented this week at the 2024 American Thyroid Association Annual Meeting. 
Anaplastic thyroid cancer has historically had very poor prognoses, with nearly 100% of cases being fatal. 
In stage IVB, the current standard of care has involved multimodal therapy, including upfront surgery when feasible, and radiation, with or without concurrent cytotoxic chemotherapy, followed by observation — but relapse rates are high, with one study showing distant metastases occurring among 72% of patients after multimodal therapy.
While adjuvant chemotherapy has been used since the 1970s, the approach has not been a part of the standard of care for stage IVB anaplastic thyroid cancer, therefore, “this is truly novel for this solid tumor,” Cabanillas explained, noting “ it appears that some clinicians at tertiary cancer institutions are already using this approach off label.”
For the study, patients with stage IVB anaplastic thyroid cancer who were involved in a prospective, phase 2 trial that closed early due to poor accrual, were combined with a retrospective cohort of consecutive patients who met the trial’s eligibility criteria. 
Overall, 16 patients were treated between March 2020 and February 2024 and matched with a control group, also of 16 patients, treated with multimodal therapy only between June 2014 and March 2024. 
For those receiving pembrolizumab, the therapy was initiated at 2-6 weeks after the completion of radiation, consisting of 400 mg intravenous administration every 6 weeks or 200 mg intravenous administration every 3 weeks, with pembrolizumab treatment offered for 1 year with the option of a second year based on patient and physician preference.
Patients in both arms had a median age of 59. In both groups, 87.5% received R0/R1 surgery, and the median dose of radiation therapy was 60 Gy in the pembrolizumab group vs 66 Gy in the control arm. The median duration of adjuvant pembrolizumab was 14 months (range, 4-26).
With a median follow-up of 21 months, the progression-free survival was not reached in the pembrolizumab group and was 5.4 months in those not receiving pembrolizumab (P =.002).
Likewise, the rate of overall survival was not reached in the pembrolizumab group and was 31 months without pembrolizumab (P =.005). 
The relapse rate was 19% (n = 3) in the pembrolizumab arm vs 82% in the control arm (P <.001). 
The 12-month survival rate between the two groups was 100% vs 80%, and for 24-month survival, the data was too early for pembrolizumab vs 52% in the control arm.
In terms of adverse events, one patient developed a case of grade 2 pneumonitis, which was treated with steroids and resulted in pembrolizumab discontinuation, while there were no other serious adverse events.
While longer follow-up is needed, encouragingly, “most patients have surpassed the 1-year post-radiation period during which they are at the highest risk of developing metastatic disease,” Cabanillas said. 
“What we don’t know is what will happen in years 2 and 3,” she added. “Only time will tell if we have cured these patients.”
Trial Recruitment a Challenge, Hindering Treatment Advances
The authors meanwhile urge societies to adopt their proposed algorithm for treatment, however, the rare nature of anaplastic thyroid cancer poses ongoing challenges in terms of developing guidelines, Cabanillas said.
“The problem with publishing anaplastic thyroid cancer trials is that they are often dismissed by high impact journals because the trials are almost never randomized control trials,” she explained. 
“These types of trials are nearly impossible to open and recruit due to the rarity of the disease.”
Even at MD Anderson, which sees more anaplastic thyroid cancer cases than any institution in the United States, “we had trouble enrolling the single arm study that is included in the abstract,” Cabanillas noted.
“However, we do have good historical data to compare to and it is the best that we can do with the number of patients we are able to recruit to trials and limited funding opportunities for this particular rare cancer.”
The bottom line, however, is that “this cancer has been neglected for too long and many patients are not even given a chance to try novel therapies,” Cabanillas said. 
That being said, the researchers are forging ahead to address the need.
In another study published by Cabanillas and her colleagues in JAMA Oncology last week, further encouraging outcomes were observed with a checkpoint inhibitor in patients stratified based on genetically-matched targeted therapy, with all also receiving the immune checkpoint inhibitor atezolizumab.
The overall survival observed across the three groups was 19 months, representing, “to our knowledge, the longest overall survival reported to date in an anaplastic thyroid cancer clinical trial,” the authors report.
Commenting on the study, Kartik Sehgal, MD, director of the Thyroid Cancer Center and a medical oncologist at the Center for Head and Neck Oncology, Dana-Farber Cancer Institute, in Boston, Massachusetts, underscored that the study “shows significant improvement in both progression-free and overall survival with use of adjuvant pembrolizumab immunotherapy in this critical patient population.”
In terms of caveats, he noted that “a major limitation of this study is the inherent bias associated with a retrospective study, but the authors did match the two groups by the treatment type,” he told Medscape Medical News.
“Nevertheless, this is very important data for our field and should spearhead a collaborative effort to launch a multicenter prospective trial for confirmation of these results.”
Sehgal noted, “In absence of a current trial, we have also been using a similar approach for our patients at our Thyroid Cancer Center at Dana-Farber Cancer Institute, based on our phase 2 trial in advanced patients with anaplastic thyroid cancer.”
Sehgal’s study was in fact published in the same recent issue of JAMA Oncology as the study from Cabanillas’ team, and an editorial in the issue provides perspective on both studies. 
“Promising results are emerging for immunotherapy in treating patients with anaplastic thyroid carcinoma,” the editorial author, Alfred King-yin Lam, MBBS, MD, PhD, of the School of Medicine and Dentistry, Griffith University, Gold Coast Campus, Southport, Australia, writes.
“Combining multiple treatment modalities, including immunotherapy, is expected to improve for patients with this aggressive cancer,” he adds.
“The timely use of predictive biomarkers, application of new technology, and clinical trials are pressing needs that will help clinicians provide better health care to patients with aggressive thyroid cancer, in particular anaplastic thyroid carcinoma.”
The study was funded by the Merck Investigator Studies Program and MP ATC Philanthropic Funds. Cabanillas’ disclosures include grants from Genentech and Merck, personal fees from Novartis during the conduct of the study, and personal fees from Bayer and Exelixis outside the study. Sehgal reports receiving research funding from Merck. Lam had no disclosures to report.
 
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