Dabrafenib plus trametinib treatment in patients with anaplastic thyroid carcinoma: an Argentinian experience.

PURPOSE: To present our real-life experience with dabrafenib and trametinib (D-T) treatment in patients with BRAF V600E-mutated ATC in Argentina. PATIENTS Y METHODS: We included five patients from four different hospitals. The median age was 70 years, and 60% were male. The performance status at diagnosis was grade 0 in 60% and grade 2 in 40% of patients. Four patients could undergo total thyroidectomy; in one of them, surgical treatment was amenable due to the indication of D-T as neoadjuvant therapy. From the total cohort, the best response to treatment was complete response in 40%, partial response in 20%, and stable disease in 20%. The median duration of response was 20 weeks, ranging from 16 to 92 weeks. All patients experienced at least one adverse event (AE). Grade ≥3 AEs were observed in two (40%) patients. They were upper gastrointestinal bleeding and subclavian vein thrombosis. The median follow-up was 20 weeks (range: 16 to 92). CONCLUSION: This report contributes to illustrate the feasibility and effectiveness of D-T treatment in five patients with loco-regionally advanced and metastatic BRAF V600E-mutated ATC in a real-life setting. A multidisciplinary approach and rapid molecular-tailored testing are essential to begin this therapeutic option.

Real-life use of lenvatinib in patients with differentiated thyroid cancer: experience from Argentina.

PURPOSE: To describe the experience with radioiodine-resistant differentiated thyroid cancer (RR-DTC) patients treated with lenvatinib in two university hospitals from Argentina. METHODS: Adult patients with a diagnosis of RR-DTC treated with lenvatinib from April 2017 to February 2020 were registered into a retrospective database. Primary objectives were assessment of progression-free survival (PFS) and tumor response evaluated according to RECIST v 1.1. Adverse events (AEs) were evaluated by using Common Terminology Criteria for Adverse Events v5.0. RESULTS: Twenty-two patients were treated with lenvatinib, 13 of whom had previously received one or more multikinase inhibitors. Median duration of treatment was 7.1 months (2.2-24). Best overall response was complete response in one patient (4.5%), partial response in seven (31.8%), stable disease in seven (31.8%), and progressive disease in six (27.3%). Median PFS was 13.7 months (95% CI 3.2-24.2). All patients experienced at least one AE. Grade ≥3 AEs were observed in eight (36.4%) patients. Hypertension was the most frequent AE (63.6%) and the most common grade ≥3 AE (22.7%). Definitive withdrawal was necessary in two patients due to recurrent proteinuria (9%). CONCLUSIONS: Tumor responses and PFS in our study were in line with other real-life clinical data and they seem to be inferior to the reported in the SELECT trial, probably related to the higher number of patients with prior MKI therapy, comorbidities, and poor performance status. Although virtually all patients experienced AEs, most of them were manageable and rarely a definitive withdrawal was necessary.

Predictors of Survival After Head and Neck Squamous Cell Carcinoma in South America: The InterCHANGE Study.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) incidence is high in South America, where recent data on survival are sparse. We investigated the main predictors of HNSCC survival in Brazil, Argentina, Uruguay, and Colombia. METHODS: Sociodemographic and lifestyle information was obtained from standardized interviews, and clinicopathologic data were extracted from medical records and pathologic reports. The Kaplan-Meier method and Cox regression were used for statistical analyses. RESULTS: Of 1,463 patients, 378 had a larynx cancer (LC), 78 hypopharynx cancer (HC), 599 oral cavity cancer (OC), and 408 oropharynx cancer (OPC). Most patients (55.5%) were diagnosed with stage IV disease, ranging from 47.6% for LC to 70.8% for OPC. Three-year survival rates were 56.0% for LC, 54.7% for OC, 48.0% for OPC, and 37.8% for HC. In multivariable models, patients with stage IV disease had approximately 7.6 (LC/HC), 11.7 (OC), and 3.5 (OPC) times higher mortality than patients with stage I disease. Current and former drinkers with LC or HC had approximately 2 times higher mortality than never-drinkers. In addition, older age at diagnosis was independently associated with worse survival for all sites. In a subset analysis of 198 patients with OPC with available human papillomavirus (HPV) type 16 data, those with HPV-unrelated OPC had a significantly worse 3-year survival compared with those with HPV-related OPC (44.6% v 75.6%, respectively), corresponding to a 3.4 times higher mortality. CONCLUSION: Late stage at diagnosis was the strongest predictor of lower HNSCC survival. Early cancer detection and reduction of harmful alcohol use are fundamental to decrease the high burden of HNSCC in South America.

Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040).

Two phase III clinical trials (CheckMate 141 and KEYNOTE 040) have independently demonstrated that overall survival (OS) in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, who have failed platinum-based therapy, can be improved with anti-PD1 monotherapy. Treatment with nivolumab or pembrolizumab in R/M HNSCC patients led to an improved OS with a hazards ratio (HR) of 0.70 (95%CI 0.51-0.96; p = 0.01) and HR of 0.80 (95%CI 0.65-0.98, p = 0.0161), respectively, as compared to standard of care (SOC) chemo monotherapy regimens (specifically, cetuximab, docetaxel, or methotrexate). The gain in OS was similar in both studies, underscoring the role of anti-PD1 drugs in R/M HNSCC patients. One of the striking discrepancies between CheckMate 141 and KEYNOTE 040 was the OS observed in the control SOC arms (6.9 months median in KEYNOTE 040 versus 5.1 months in CheckMate 141), which inadvertently set a higher threshold in the bio-statistical analysis of KEYNOTE 040 so that the clinical outcome of every patient was influential in the analysis. We perform a comparative analysis of the two studies to identify potential factors in the control arm that can impact clinical trial bio-statistical outcomes and which may have implications for future immunotherapy clinical trial designs.

Experiencia de 20 años en tratamiento conservador del cáncer de laringe estadio III y IV operable del equipo multidisciplinario del Instituto Angel H Roffo / 20 Years experience with organ preservation in resecable stage III and IV laryngeal cancer by a multidisciplinary of them the

The classic treatment of the laryngeal resectable stage III and IV epi-dermoid cancer is: surgery followed by adjuvant radiotherapy. Only on scarce occasions these patients can accede to organ preservation conserving correct phonetics and deglution with absence of aspiration. In most of the occasions the procedure of choice is total laryngectomy with or without cervical emptying if it is necessary. Since the end of the '80s. we have developed strategies for organ preservation of the tumors of the head and neck. Despite the implementation of the neoadjuvant chemotherapy and the later use of chemoradiotherapy simultaneously or the introduction of monoclonal antibodies anti EGFR (anti epidemic growth receptor factor), the rate of survival of the tumors in resectabale stage III and IV epidermoid carcinoma remains stable. The authors present their experience with the management of these patients, considering that the two main objectives for the development of new strategies for the treatment of laryngeal cancer are to raise the rate of survival, and the rate of larynx preservation. La rynx preservation using induction chemotherapy plus radiation therapy, and preservation in cases of advance laryngeal cancer treated with platinum, are also considered. Preservation using neoadjuvant chemotherapy is also detailed. The authors presents their experience with the management of these patients.