Aleya Tadi L. Garcia, MD; Ria Mari S. Siao, MD
Thyroid cancer is the most common endocrine-related malignancy in the Philippines.1 In a systematic review published by San Juan and Paz-Pacheco, it is stated that the average annual incidence of thyroid cancer is 7.3 per 100,000 for Filipino males and 17.3 per 100,000 for Filipino females.2 Anaplastic thyroid cancer (ATC) is an undifferentiated form of thyroid cancer which is rare and accounts for ~2% of all thyroid cancers, but is one of the most aggressive solid tumors, responsible for 14% – 50% of the total annual mortality associated with thyroid cancer.3 Median survival from diagnosis is 5 months, with a 1-year survival rate of 20%.4 In a 2019 Philippine study which examined 1618 thyroid specimens that underwent histopathologic confirmation, ATC was present in 0.7% of the specimens.5
At the time of diagnosis, majority of patients with ATC present with extensive locoregional invasion and distant metastases.3,4 Because of the rapid onset of complications and the short median survival from diagnosis, expeditious treatment initiation is critical in patients diagnosed with ATC.6 There is no definitive management and treatment is generally palliative, although in certain cases a combination of surgery, radiotherapy, and chemotherapy has resulted in prolonged patient survival.3 In circumstances when the disease is considered unresectable or high-risk, neoadjuvant radiation and/or chemotherapy can be considered, permitting delayed primary resection if needed.6,7 However, anthracyclines (doxorubicin) and taxanes (paclitaxel, docetaxel) have modest and only transient clinical activity in advanced ATC.6
In a recent multicenter, nonrandomized, phase II, open-label trial called the Rare Oncology Agnostic Research (ROAR) basket study, they examined the efficacy and safety of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers, namely: anaplastic thyroid carcinoma, biliary tract cancer, gastrointestinal stromal tumor, adenocarcinoma of the small intestine, low-grade glioma, high-grade glioma, hairy cell leukemia and multiple myeloma.8 Dabrafenib and trametinib were initially indicated for use in patients with advanced melanoma. The ATC cohort of the ROAR study had 36 patients with unresectable or metastatic ATC who received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily orally until disease progression, unacceptable toxicity, or death. 4 Findings in this trial shows an overall response rate of 56% and 12- month duration of response rate of 50%. The respective 12-month progression-free survival and overall survival rates of 43.2% and 51.7% are notable, considering that the median overall survival rate in patients with ATC was historically < 6 months.4,8 The most common adverse effects were fatigue, pyrexia and nausea, all of which resolve with temporary dose interruption.4 Because of these findings, the latest European Society of Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) clinical practice guidelines recommended BRAF molecular testing as part of the workup for patients diagnosed with ATC.
In 2022, Dabrafenib and Trametenib received US FDA approval for the treatment of advanced solid tumors found to have mutation in the BRAF gene, including those with ATC.9 Though promising for the local practice, as of this writing, due to the unavailability of the aforementioned drugs in the Philippines, no local case studies nor data are available examining their role in the treatment of ATC.
References:
1. Sarigumba MB, Isidro MJC. Undifferentiated Thyroid Carcinoma With Anaplastic Features in a 78-Year- Old Filipino Female: A Case Report. J Endocr Soc. 2021; 5(Suppl 1): A903–4. DOI: 10.1210/jendso/bvab048.1844. PMCID: PMC8135547.
2. San Juan MD, Paz-Pacheco E. Incidence, Recurrence and Mortality Among Filipinos With Differentiated Thyroid Cancer: A Systematic Review. J ASEAN Fed Endocr Soc. 2023; 38(1):100-107. DOI: 10.15605/jafes.038.01.14. PMID: 37252408. PMCID: PMC10213166.
3. Lo TE, Jimeno CA, Paz-Pacheco E. Anaplastic Thyroid Cancer: Experience of the Philippine General Hospital. Endocrinol Metab (Seoul). 2015; 30(2):195-200. DOI: 10.3803/EnM.2015.30.2.195. PMID: 26194079. PMCID: PMC4508264.
4. Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib plus trametinib in patients with BRAF V600E- mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study. Ann Oncol. 2022; 33(4): 406-415. DOI: 10.1016/ j.annonc.2021.12.014. PMID: 35026411. PMCID: PMC9338780.
5. Caguioa PB, Bebero KGM, Bendebel MTB, Saldana JS. Incidence of thyroid carcinoma in the Philippines: a retrospective study from a tertiary university hospital. Ann Oncol. 2019; 30(9): ix104. DOI:10.1093/annonc/mdz428.024.
6. Bible KC, Kebebew E, Brierley J, et al. 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid. 2021; 31(3):337-386. DOI: 10.1089/thy.2020.0944.
7. National Comprehensive Cancer Network. (2024). Thyroid cancer (version 4.2024). https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. Accessed December 26 2024.
8. Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. Nat Med. 2023; 29, 1103–1112. DOI: 10.1038/s41591-023-02321-8. PMID: 37059834; PMCID: PMC10202803.
9. Winstead E. Dabrafenib–Trametinib combination approved for solid tumors with BRAF mutations. National Cancer Institute. July 21, 2022. https://www.cancer.gov/news-events/cancer-currents- blog/2022/fda-dabrafenib-trametinib-braf-solid-tumors. Accessed December 28, 2024.
