Sunitinib for the treatment of metastatic gastrointestinal stromal tumors: the effect of TDM-guided dose optimization on clinical outcomes.

BACKGROUND: Sunitinib is an oral anticancer drug approved for the treatment of among others gastrointestinal stromal tumor (GIST). Previous analyses demonstrated an exposure-response relationship at the standard dose, and minimum target levels of drug exposure have been defined above which better treatment outcomes are observed. Therapeutic drug monitoring (TDM) could be used as a tool to optimize the individual dose, aiming at sunitinib trough concentrations ≥37.5 ng/ml for continuous dosing. Nonetheless, data on the added value of TDM-guided dosing on clinical endpoints are currently lacking. Therefore, we evaluate the effect of TDM in patients with advanced and metastatic GIST treated with sunitinib in terms of efficacy and toxicity. PATIENTS AND METHODS: A TDM-guided cohort was compared to a non-TDM-guided cohort in terms of median progression-free survival (mPFS) and overall survival (mOS). Also, mPFS between patients with and without dose-limiting toxicities (DLTs) was compared. Patients in the prospective cohort were included in two studies on TDM-guided dosing (the DPOG-TDM study and TUNE study). The retrospective cohort consisted of patients from the Dutch GIST Registry who did not receive TDM-guided dosing. RESULTS: In total, 51 and 106 patients were included in the TDM-guided cohort and non-TDM-guided cohort, respectively. No statistical difference in mPFS was observed between these two cohorts (39.4 versus 46.9 weeks, respectively; P = 0.52). Patients who experienced sunitinib-induced DLTs had longer mPFS compared to those who did not (51.9 versus 28.9 weeks, respectively; P = 0.002). CONCLUSIONS: Our results do not support the routine use of TDM-guided dose optimization of sunitinib in patients with advanced/metastatic GIST to improve survival.

Communication about Prognosis during Patient-Initiated Second Opinion Consultations in Advanced Cancer Care: An Observational Qualitative Analysis.

Prognostic communication is essential for patients with advanced cancer to enable informed medical decision-making and end-of-life planning. Discussing prognosis is challenging, and might be especially complex for oncologists conducting a second opinion (SO). Survival data are often lacking, and consulting oncologists need to consider previously conveyed information and patients' relationship with the referring oncologist. We qualitatively investigated how advanced cancer patients and consulting oncologists discuss prognosis during audio-recorded SO consultations (N = 60), including prognostic information received from the referring oncologist. Our results show that patients regularly expressed implicit cues to discuss prognosis or posed explicit questions tentatively. Consulting oncologists were mostly unresponsive to patients' cues and cautious to prognosticate. They also seemed cautious when patients brought up the referring oncologist. Consulting oncologists checked which prognostic information patients had received from the referring oncologist, before estimating prognosis. They agreed with the first opinion or rectified discrepancies carefully. Altogether, this study exposes missed opportunities for open prognostic discussions in SOs. Consulting oncologists could explicitly explore patients' information preferences and perceptions of prognosis. If desired, they can provide tailored, independent information to optimise patients' prognostic awareness and informed medical decision-making. They may additionally support patients in dealing with prognosis and the uncertainties associated with it.