Anita K. Ying

Efficacy and Tolerability of Vemurafenib in Patients with BRAFV600E -Positive Papillary Thyroid Cancer: M.D. Anderson Cancer Center Off Label Experience

CONTEXT Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation. OBJECTIVE To determine the efficacy and safety of vemurafenib when used outside of a clinical trial. DESIGN A retrospective review at MD Anderson Cancer Center. METHODS The best responses were evaluated using RECIST v1.1. A single radiologist reviewed all images. Adverse events (AEs) were evaluated using CTCAE v.4.0. RESULTS We identified 17 patients with advanced PTC harboring the BRAF(V600E) mutation who were treated with vemurafenib outside of a clinical trial. Median age at diagnosis was 63 years, and 53% were male. At vemurafenib start, 3 (18%) patients had disease confined to the neck, and 14 (72%) had distant metastases. Tyrosine kinase inhibitors had been previously administered to 4 (24%) patients. Two (12%) patients discontinued vemurafenib because of AEs before restaging. Best response: partial response (PR) in 7/15 (47%) and stable disease (SD) in 8/15(53%) patients. The rate of durable response (PR plus SD ≥ 6 months) was 67%. Median time to treatment failure was 13 months. There was no association between change in thyroglobulin and tumor size. Drug discontinuation, drug interruptions, and dose reductions were needed in 5 (29%), 13 (76%), and 10 (59%) patients, respectively. Most common AEs were fatigue (71%), weight loss (71%), anorexia (65%), arthralgias (59%), hair loss (59%), rash (59%), hand-foot syndrome (53%), calluses (47%), diarrhea (47%), fever (41%), dry mouth (35%), nausea (35%), and verrucous keratosis (35%). Grade ≥ 3 AEs were present in 8 (47%) patients. CONCLUSIONS Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation. Our results are similar to those reported in a phase II clinical trial and support the potential role of vemurafenib in this patient population.

Cushing's syndrome secondary to ectopic ACTH secretion: The University of Texas MD Anderson Cancer Center Experience

Cushing syndrome (CS) secondary to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) has been described in association with a variety of tumors. The current experience with this syndrome was based on a few case series and individual case reports. Limited data were available about the tumors associated with CS‐EAS in a cancer center setting. In this report, the authors have described their experience with CS‐EAS at The University of Texas MD Anderson Cancer Center to further enhance the current understanding and management of this syndrome.

Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion: the University of Texas MD Anderson Cancer Center Experience.

Cushing syndrome (CS) secondary to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) has been described in association with a variety of tumors. The current experience with this syndrome was based on a few case series and individual case reports. Limited data were available about the tumors associated with CS‐EAS in a cancer center setting. In this report, the authors have described their experience with CS‐EAS at The University of Texas MD Anderson Cancer Center to further enhance the current understanding and management of this syndrome.

Role of Salvage Targeted Therapy in Differentiated Thyroid Cancer Patients Who Failed First-Line Sorafenib

CONTEXT Sorafenib, a tyrosine kinase inhibitor, is a common first-line therapy for advanced differentiated thyroid cancer (DTC). However, responses are not durable and drug toxicity remains a problem. OBJECTIVE The objective of the study was to determine the efficacy of salvage therapy after first-line sorafenib failure. DESIGN This was a retrospective review at M. D. Anderson Cancer Center from January 2005 to May 2013. PATIENTS The study included patients with metastatic DTC who received salvage therapy after their initial sorafenib failure (group 2). PATIENTS who received first-line sorafenib only (group 1) were evaluated for comparison of overall survival (OS). OUTCOME MEASURES Progression-free survival, best response, and median OS were measured. RESULTS Sixty-four patients with metastatic, radioactive iodine refractory DTC were included; 35 were in group 1 and 25 were in group 2, and the groups were well balanced. Median OS of all 64 patients receiving first line sorafenib was 37 months; median OS was significantly longer with salvage therapy compared with sorafenib alone (58 vs 28 months, P = .013). In group 2, 17 patients were evaluable for best response, although two patients had toxicity with sorafenib, which was discontinued before restaging. Best responses with first-line sorafenib were partial response in 2 of 15 (13%), stable disease in 10 of 15 (67%), and progressive disease in 3 of 15 (20%) patients. With salvage therapy, partial responses were seen in 7 of 17 (41%) and stable disease in 10 of 17 (59%) patients. Median progression-free survival was 7.4 months with first-line sorafenib and 11.4 months with salvage therapy. Salvage therapy included sunitinib (n = 4), pazopanib (n = 3), cabozantinib (n = 4), lenvatinib (n = 3), and vemurafenib (n = 3). CONCLUSIONS Other targeted agents are effective salvage treatments after sorafenib failure, despite similar mechanisms of action, and should be offered to patients who are able to receive salvage therapy.

Do the recent American Thyroid Association (ATA) Guidelines accurately guide the timing of prophylactic thyroidectomy in MEN2A

BACKGROUND In 2009, the American Thyroid Association (ATA) published consensus guidelines for timing of prophylactic thyroidectomy (PrThy) for treatment of hereditary medullary thyroid cancer (MTC). The aim of this study was to assess whether the clinical guidelines outlined in the ATA recommendations added to the specific mutation risk level could predict the presence of MTC on final pathology. METHODS A retrospective study was performed of patients undergoing PrThy. We evaluated mutation-based risk levels in combination with 2009 ATA guidelines for resection. RESULTS Overall, 54 patients underwent PrThy between 1972 and 2009. The median age at PrThy was 11.5 years (range, 2-68). Only 4 patients (8%) underwent PrThy prior to age 5 years. Most patients with MTC (16/22, 73%) had a level C mutation, and the youngest age of MTC in a level C mutation carrier was 5 years. The youngest age of MTC in level A or B carriers was 15 years. The single factor that predicted an overall decreased risk of MTC at the time of PrThy was meeting all ATA mutation-based postponement guidelines for surgical intervention (P = .04). CONCLUSION ATA guidelines that includes risk assessment of RET mutation are important in predicting the presence of MTC in patients who are candidates for prophylactic thyroidectomy and in determining the timing of operative resection.

Efficacy and Tolerability of Different Starting Doses of Sorafenib in Patients With Differentiated Thyroid Cancer

Sorafenib has proven efficacy in advanced differentiated thyroid cancer (DTC), but many patients must reduce the dose or discontinue treatment because of toxicity. The tolerability and efficacy of lower starting doses of sorafenib for DTC remain largely unstudied. Methods. We retrospectively examined overall survival, time to treatment failure, time to progression, discontinuation rates, and dose-reduction and interruption rates in patients with metastatic DTC treated with first-line sorafenib outside of a clinical trial. Two patient groups were compared; group 1 received the standard starting dose of 800 mg/day, and group 2 received any dose lower than 800 mg/day. Results. We included 75 adult patients, with 51 in group 1 and 24 in group 2. Mean age at diagnosis was 54 years, and 56% were male. The most common histologies included 43% papillary thyroid cancer of the conventional type, 15% papillary thyroid cancer of the follicular variant, and 15% Hürthle cell carcinoma. Time to treatment failure was 10 months (95% confidence interval [CI]: 5.6-14.3) in group 1 and 8 months (95% CI: 3.4-12.5) in group 2 (p = .56). Median overall survival was 56 months (95% CI: 30.6-81.3) in group 1 and 30 months (95% CI: 16.1-43.8) in group 2 (p = .08). Rates of discontinuation due to disease progression were 79% in group 1 and 91% in group 2, and 21% in group 1 and 9% in group 2 (p = .304) stopped treatment because of toxicity. Dose-reduction rates were 59% and 43% (p = .29), and interruption rates were 65% and 67% (p = .908) in group 1 and group 2, respectively. Conclusion. Efficacy and tolerability of sorafenib in treatment-naïve DTC patients does not appear to be negatively influenced by lower starting daily doses.

Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion

Cushing syndrome (CS) secondary to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) has been described in association with a variety of tumors. The current experience with this syndrome was based on a few case series and individual case reports. Limited data were available about the tumors associated with CS‐EAS in a cancer center setting. In this report, the authors have described their experience with CS‐EAS at The University of Texas MD Anderson Cancer Center to further enhance the current understanding and management of this syndrome.

Facilitating anaplastic thyroid cancer specialized treatment: A model for improving access to multidisciplinary care for patients with anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer. Several treatment trials are available, but the number of eligible patients to participate is very low because of the rarity and aggressiveness of the disease.