KEY TAKEAWAYS
- In the INVICTUS phase 3 trial, ripretinib, a novel switch-control kinase inhibitor that inhibits KIT and PDGFRA signalling, demonstrated increased median progression-free survival and prolonged overall survival vs. placebo in patients with ≥ fourth-line advanced GIST.
- QoL was assessed using patient-reported outcome (PRO) measures, including the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQoL 5-Dimension 5-Level (EQ-5D-5 L) in the INVICTUS trial (NCT03353753).
- Analysis of covariance (ANCOVA) models showed that patients receiving ripretinib maintained QoL from baseline to cycle 2, day 1, while QoL declined with placebo, resulting in clinically significant differences between treatments (nominal P < 0.01).
- The most common treatment-emergent adverse event with ripretinib was alopecia; however, QoL was similarly maintained out to treatment cycle 10, day 1 in patients receiving ripretinib who developed alopecia and those who did not.
- PRO assessments in the INVICTUS trial suggest that patients on ripretinib maintain their QoL out to cycle 2, day 1 and even up to cycle 10, day 1 (approximately 8 months) even if they develop alopecia, indicating that ripretinib may have a positive impact on the QoL of patients with advanced GIST.
Inhibiting KIT and PDGFRA signaling, ripretinib is a new switch-control kinase inhibitor. Ripretinib improved median progression-free survival and enhanced overall survival against placebo in fourth-line advanced GIST in the INVICTUS phase 3 trial. In addition, they present an exploratory analysis of the effect of alopecia on QoL and a defined analysis of QoL as measured by patient-reported outcome (PRO) measures.
Quality of life was measured in the INVICTUS trial (NCT03353753) with the help of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30; physical function, role function, overall health, and overall QoL) and the EuroQoL 5-Dimension 5-Level Questionnaire (EQ-5D-5 L; visual analog scale). Score changes from baseline to treatment cycle 2, day 1 were compared between ripretinib and placebo using analysis of covariance (ANCOVA) models. In addition, the effect of alopecia on quality of life was evaluated using repeated measures models in the ripretinib group.
Quality of life (as measured by the EORTC QLQ-C30 and EQ-5D-5 L PRO measures) was maintained in ripretinib-treated patients from baseline to cycle 2, day 1, while it declined in placebo-treated patients, yielding statistically and clinically significant differences between treatments (nominal P<0.01). Alopecia was the most common treatment-emergent adverse event with ripretinib. However, patients who developed alopecia and those who did not have equivalent QoL continued to treatment cycle 10, day 1.
Patient-reported outcome (PRO) analyses from the INVICTUS trial showed that ripretinib-treated individuals had higher C2D1 QoL than placebo-treated patients. In addition, those treated with ripretinib who developed alopecia still had a high quality of life (QoL) longitudinally until cycle 10, day 1 (about 8 months; beyond the point of median progression-free survival with ripretinib [6.3 months]).
Source: https://pubmed.ncbi.nlm.nih.gov/36514034/
Clinical trial:https://clinicaltrials.gov/ct2/show/NCT03353753
Schöffski, P., George, S., Heinrich, M.C., Zalcberg, J.R., Bauer, S., Gelderblom, H., Serrano, C., Jones, R.L., Attia, S., D’Amato, G., Chi, P., Reichardt, P., Becker, C., Shi, K., Meade, J., Ruiz-Soto, R., Blay, J.-Y. and von Mehren, M. (2022). Patient-reported outcomes in individuals with advanced gastrointestinal stromal tumor treated with ripretinib in the fourth-line setting: analysis from the phase 3 INVICTUS trial. BMC Cancer, 22(1). doi:https://doi.org/10.1186/s12885-022-10379-9.
