Endocrine Abstracts

Background: Tyrosine kinase inhibitors (TKIs) have been shown to improve progression-free survival (PFS) in advanced thyroid cancer (TC), though their administration is burdened by multiple adverse events (AEs). Maintaining optimal drug dosage for optimal tumour response can be challenging and prehabilitation, aiming to improve patient well-being before cancer treatment, is becoming relevant in this context. While some information exists for other cancers, no data are available for advanced TC patients treated with TKIs.

Objectives: To evaluate the impact of physical activity and its maintenance on the safety and efficacy of TKIs in advanced TC.

Methods: This preliminary analysis involved 18 patients: 10 Differentiated TCs (DTCs), 3 Poorly Differentiated TCs (PDTCs), 5 Medullary TCs (MTCs), treated for an average time of 45 (6-180) months with Lenvatinib (n = 12), Vandetanib (n = 4), and Cabozantinib (n = 2). Three modified long-form International Physical Activity Questionnaires (IPAQ) were retrospectively administered for each patient at different time points (T0, before TKI treatment; T1, intermediate; T2, at last follow-up). Metabolic equivalents (METS) were calculated for each time point and the patients were consequently classified as low, moderately, or highly active. Quality of Life Questionnaire-Core30 (QLQ-C30) and QLQ-Thyroid Cancer Module (QLQ-THY34) were also administered. Basal Eastern Cooperative Oncology Group Performance Status (ECOG PS) was assessed, and AEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE v5.0). Tumour response was evaluated following Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Results: A reduction in METS during treatment was significantly associated with AEs of grade ≥ 3 (P = 0.04, from T0 to T1 and P = 0.02 from T0 to T2). Among all AEs, fatigue (grade<3) mostly limited patients’ activity status during TKI treatment. High METS levels at T2 correlated statistically with higher QLQ-C30 functional state points (P = 0.05, r = 0.49). Moreover, being highly active at T2 was associated with fewer AEs compared to low active patients (40 vs 82%, P = 0.09). Patients with a highly active lifestyle at T0 experienced fewer TKI interruptions (43 vs 82%, P = 0.09) and TKI dose reductions (20 vs 64%, P = 0.1). Progressive disease (PD) occurred less frequently in patients who remained highly active through treatment (12 vs 38%, P = 0.2).

Conclusions: Our data show for the first time that the preservation of physical activity is associated with milder AEs, thus reducing the need for TKI reduction/interruptions, improving PFS. This preliminary study gives the opportunity for wider and prospective research on the impact of (pre)habilitation in patients undergoing systemic treatment for advanced TC.