Table 2:

Treatment history of patients receiving kinase inhibitor (KI) therapy

Case #, Diagnosis	Pre-KI Management	Kinase Inhibitor Therapy and Responsea			Toxicity (gradeb)
		First Regimen	Second Regimen	Third Regimen
1, PDTC	T, M (STRN-ALK fusion, TP53 c.772G>C)	Sorafenib 400 mg BID, stopped after 19 days due to ischemic stroke.	Crizotinib 250 mg BID, stopped after 11 months due to PD. The BOR was SD.	Lenvatinib 14mg daily while on hospice, stopped after 1 month for lethargy.	Crizotinib: fatigue (1). Lenvatinib: small oral ulcers.
13, PTC	T, RAI, M (PPL-NTRK1 fusion)	Trametinib 2 mg daily (redifferentiation therapy) for 30 days, followed by RAI; restaging imaging showed PD.	Larotrectinib* 100 mg BID; CR after 10 cycles; now 45 cycles into therapy with ongoing CR.	-	Trametinib: fatigue (1), dysphagia (1), acneiform eruption (3). Larotrectinib: fatigue (1), muscle cramping (1), dysgeusia (1).
16, PTC	T, RAI, revision neck dissection, M (TPR-NTRK1 fusion)	Larotrectinib* 100 mg BID; now on cycle 21 with ongoing PR (33% decrease).	-	-	Fatigue (1), joint pain (1); transaminitis (1).
20, PTC	T, RAI, resection and irradiation of brain metastasis, M (EML4-NTRK1 fusion; pTERT c.−124C >T; MEN1 frameshift deletion)	Entrectinib** 400 mg daily; now on cycle 38 with ongoing PR (69% decrease).	-	-	Orthostatic hypotension (3), gait disturbance (2), exertional dyspnea (1), fatigue (1), anemia (2), leukopenia (1), serum creatinine elevation (1).
24, SC	T, RAI, irradiation of cervical recurrence; M (ETV6-NTRK3 fusion)	Larotrectinib* 100 mg BID; now on cycle 29 with ongoing PR (100% decrease of measurable tumor and undetectable thyro-globulin, but deemed PR due to small persistent lung lesions likely granulomata).	-	-	Instability (1), hypophosphatemia (1).
31, ATC	T, RAI, radiosurgery of brain metastasis, one cycle of Adriamycin/Taxotere; M (CCDC6-RET, pTERT, TP53, TSC2, PTCH1 mutations)	Selpercatinib*** 160 mg BID; now on cycle 28 with ongoing PR (64% decrease).	-	-	Bowel edema (1).
41, PTC	T, RAI, resection and irradiation of paraspinal metastasis, M (CCDC6-RET fusion)	Selpercatinib*** 160 mg BID; now on cycle 18 with ongoing PR (61% decrease).	-	-	Hypertension (1).
52, ATC	T, RAI, resection and irradiation of metastases, M (ERC1-RET fusion; pTERT, PTCH1 and NF2 mutations)	Lenvatinib 14mg daily, with a BOR of SD, stopped after 20 months of treatment due to PD.	Selpercatinib*** 160 mg BID, stopped due to PD after 22 cycles (21 months). The BOR was PR (63% decrease). Posttreatment M: new EGFR copy number gain.	Cabozantinib 40 mg daily for 3 months followed by 60 mg daily for one month, then stopped due to wound infection; restaging imaging showed PD. Pembrolizumab was subsequently started one month prior to death.	Lenvatinib: hand-foot syndrome (1); transaminitis (1), hyperbilirubinemia (2). Selpercatinib: fatigue (1), transaminitis (1), hypertension (1), thrombocytopenia (1). Cabozantinib: transaminitis (2).
53, PDTC	Radiotherapy; M (NCOA4-RET fusion).	Lenvatinib 24 mg daily, stopped after five months due to PD.	Selpercatinib*** 60–80 mg BID for 8 cycles, followed by 160 mg BID for 10 cycles and then stopped due to PD. The BOR was PR (72% decrease).	Cabozantinib 40 mg daily for 6 months, then combined with pembrolizumab for 2 months before patient died of advanced disease.	Lenvatinib: fatigue (1). Selpercatinib: diarrhea (1), transaminitis (3). Cabozantinib: diarrhea (2), mucositis (1).
58, PTC	T, RAI, radiotherapy, M (NCOA4-RET fusion)	Lenvatinib 24 mg daily; PD leading to death 8 months after treatment initiation.	-	-	None documented.

Abbreviations: T, thyroidectomy; M, molecular profiling of tumor (see text for alteration details); BID, twice daily; RAI, radioactive iodine; BOR, best overall response; SD, stable disease; PD, progressive disease; CR, complete response; PR, partial response; PTC, papillary thyroid carcinoma; PDTC, poorly differentiated thyroid carcinoma; SC, secretory carcinoma; ATC, anaplastic thyroid carcinoma.

^aResponse was evaluated based on the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1.

^bBased on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. ClinicalTrials.gov identifiers:

^*NCT02576431;

^**NCT02568267;

^***NCT03157128.