Exp Clin Endocrinol Diabetes 2015; 123 - OP1_03
DOI: 10.1055/s-0035-1547604

Prognostic and predictive factors correlated with treatment outcomes for radioactive iodine-refractory differentiated thyroid cancer (RAI-RDTC) patients receiving Sorafenib or placebo on the phase III decision trial

R Paschke 1, M Schlumberger 2, R Elisei 3, F Pacini 4, B Jarzab 5, L Giannetta 6, L Bastholt 7, C de la Fouchardiere 8, FP Worden 9, YK Shong 10, J Smit 11, C Kappeler 12, I Molnar 13, MF Brose 14
  • 1University of Leipzig; Department of Internal Medicine, Neurology and Dermatology; Division of Endocrinology and Nephrology
  • 2Department of Nuclear Medicine and Endocrine Oncology; Institut Gustave Roussy and University Paris Sud
  • 3Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
  • 4Section of Endocrinology, University of Siena, Siena, Italy – Siena
  • 5Msc Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Department of Nuclear Medicine and Endocrine Oncology
  • 6Ospedale Niguarda Ca' Granda, Milan, Italy
  • 7Odense University Hospital, Odense C, Denmark
  • 8Consortium Cancer Thyroïdien, Hospices Civils-Centre Anticancéreux, Lyon, France
  • 9University of Michigan Health System, Ann Arbor, MI
  • 10Asan Medical Center; University of Ulsan College of Medicine
  • 11Department of General Internal Medicine, Radboud University Nijmegen Medical Centre
  • 12Bayer Pharma AG, Berlin, Germany
  • 13Bayer Healthcare Pharmaceuticals, Whippany, Nj
  • 14Department of Otorhinolaryngology: Head and Neck Surgery, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pa, USA

[15:50 – 16:00]
Background:

The DECISION trial established that sorafenib prolonged progression-free survival (PFS) compared to placebo in patients with progressive RAI-rDTC (Lancet 2014). Here we sought to identify prognostic and predictive factors correlated with treatment outcomes.

Methods:

Multivariate Cox proportional hazards models adjusted for treatment effect and subgroup analyses defined by maximum target lesion size and existence of disease-related symptoms were used to explore the relationship between clinical baseline variables and PFS. Patients were deemed symptomatic at entry if they had symptoms/findings consistent with thyroid cancer reported in the medical history or pre-treatment adverse event dataset.

Results:

A total of 417 patients were randomized to receive placebo (n = 210) or sorafenib (n = 207). Multivariate Cox model analyses indicated that lower maximum individual target lesion size, lower number of lesions, thyroglobulin levels at baseline less than the median (486 ng/ml) and region Asia versus Europe and North America were prognostic for longer PFS in placebo patients and in all patients when adjusted for treatment. Subgroup analyses indicated that patients whose maximum individual target tumor size were < 1.5 cm had longer PFS and appeared to have less benefit from sorafenib treatment than patients with lesions ≥1.5 cm. Lesions ≥1.5 cm as well as lung metastases were predictive for better treatment effect with sorafenib. Both symptomatic and asymptomatic patients at entry had improved PFS following treatment with sorafenib.

Conclusions:

Maximum tumor size, number of lesions, thyroglobulin levels at baseline and geographic regions were prognostic for longer PFS in RAI-rDTC patients. Individual tumor size ≥1.5 cm and lung-only metastases were predictive for better treatment effect with sorafenib. Patients appeared to benefit from sorafenib treatment irrespective of disease-related symptoms at baseline. Thus, based on these post hoc exploratory analyses, patients with progressive RAI-rDTC and maximum tumor size < 1.5 cm appear to have a good prognosis and may be candidates for “watch and wait” before initiating sorafenib.