Prognostic factors in patients with advanced differentiated thyroid cancer treated with multikinase inhibitors – a single Brazilian center experience

Abstract

Objective: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. Subjects and methods: We reviewed the records of all patients with MKItreated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. Results: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twentytwo (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). Conclusion: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.

Ten years’ real-life experience on the use of multikinase inhibitors in patients with advanced differentiated thyroid cancer

“…In our cohort, patients who received sorafenib demonstrated an ORR of 9%. This aligns with ndings from other real-world studies, which have reported ORRs ranging from 11-25% [14][15][16][17], as well as with results from the DECISION trial, where patients exhibited a PR of 12% without any CRs [3]. In contrast, our group of patients treated with lenvatinib exhibited a lower ORR compared to what was reported in the SELECT phase III study and in non-trial settings (ranging from 33-69%) [4,[18][19][20][21][22][23][24][25].…”

“…The adverse event (AE) pro les of sorafenib and lenvatinib observed in our study were consistent with ndings from clinical trials and other retrospective cohorts [3,4,[14][15][16][17][18][19][20][21][22][23][24][25]. Both tyrosine kinase inhibitors (TKIs) exhibited high percentages of AEs (97% with sorafenib and 100% with lenvatinib) and serious AEs (56% with sorafenib and 65% with lenvatinib), with no statistical difference observed between the groups.…”

“…Considering all lines of treatment, 32% of patients from our cohort achieved an OR, and the PFS and OS rates were 32 and 39 months, respectively. Our results coincide with other institutional experiences [15][16][17][18][19][20][21][22][23][24][25] and this real-world data serve to guide the discussions within the medical team and with the patients regarding the initiation of systemic therapy in RR-DTC.…”

“…Although no prospective randomized comparative analysis between sorafenib and lenvatinib has been published, a few retrospective studies have aimed to compare these two tyrosine kinase inhibitors (TKIs) [27,28] The median progression-free survival (PFS) observed with sorafenib (15 months) and lenvatinib (22 months) in our study aligns closely with ndings reported in both clinical trials and real-world studies [3,4,[14][15][16][17][18][19][20][21][22][23][24][25]. In the DECISION trial, the median PFS following sorafenib treatment was reported as 10.8 months [3], while observational cohorts reported a range from 8 to 22 months [14][15][16][17]. Similarly, the median PFS in the SELECT trial was 18.3 months [4], with real-world studies reporting a range of 10 to 18 months [18][19][20][21][22][23][24][25].…”

State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer

“…Prognostic factors of better outcome with MKIs therapy were identified, such as the absence of 18FDG uptake on target lesions, lower maximum standardized uptake values on positron emission tomography (PET-CT), presence of lung-only metastasis, and lower Tg during treatment [ 86 ]. In lenvantinib-treated patients, the appearance of HFS was correlated with a good prognosis, as opposed to fistula formation or severe tumour regrowth after drug discontinuation, which were associated with poor prognosis [ 87 ].…”