Jaume Capdevila, José Manuel Trigo, Javier Aller, José Luís Manzano, Silvia García Adrián, Carles Zafón Llopis, Òscar Reig, Uriel Bohn, Teresa Ramón y Cajal, Manuel Duran-Poveda, Beatriz González Astorga, Ana López-Alfonso, Javier Medina Martínez, Ignacio Porras, Juan Jose Reina, Nuria Palacios, Enrique Grande, Elena Cillán, Ignacio Matos and Juan Jose Grau
Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012–November 2014).
Subjects and Methods
47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n = 34) or medullary thyroid cancer (MTC, n = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form.
Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0–24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1–12.2) (DTC: 7.4 months (95% CI: 3.1–11.8) and MTC: 9.4 months (95% CI: 4.8–13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%).
Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies.
Carmela Iglesias Felip, Carles Zafon Llopis, Jordi Temprana-Salvador, Amparo García-Burillo, Xavier Serres Créixams, Enric Caubet Busquet, Isabel Roca Bielsa, Jordi Mesa Manteca, Joan Castell Conesa, José Manuel Fort López-Barajas, Ricardo Pujol-Borrell, Santiago Ramon y Cajal Agüeras and Oscar González López
Lymphadenectomy in papillary thyroid carcinoma (PTC) is controversial. It is indicated whenever metastases have been proven before or during surgery and as a prophylactic treatment in high-risk patients. However, 30–50% of cN0 patients become pN1 postoperatively. In PTC, selective-sentinel-lymph-node-biopsy (SLNB) with conventional intraoperative analysis is 8% false negative. One-step nucleic acid amplification (OSNA) is a molecular technique which allows real-time detection of mRNA encoding for cytokeratin 19. OSNA has been introduced in intraoperative analysis of several tumors to reduce false-negative rates and distinguish micrometastasis from macrometastasis. Our objective was to evaluate the impact of the introduction of OSNA in the intraoperative evaluation of the sentinel node (SN) in PTC.
We analyzed a series of 35 patients subjected to SLNB.
All the dissected nodes, SN and non-SN, were evaluated with OSNA and cytology.
We obtained a total of 110 SN. SLNB proved positive in 14 patients (40%) with cytology and in 23 (65.7%) with OSNA (P < 0.001). In the 29 patients with subsequent lymphadenectomy we obtained 360 lymph nodes ((52 positive in cytology (14.4%) and 107 in OSNA (29.7%)). Lymphadenectomy proved positive in 16 patients according to cytology (55%) and in 24 according to OSNA (83%) (P = 0002). The majority of patients with micrometastasis in SN showed only micrometastasis in lymphadenectomy.
The present study shows selective-sentinel-lymph-node-biopsy with one-step nucleic acid amplification technique to be feasible in papillary thyroid carcinoma. The quantitative nature of one-step nucleic acid amplification paves the way toward a more personalized surgical approach, limiting lymphadenectomy to patients with intraoperative evidence of macrometastasis in the sentinel node.