Abstract 64P
Background
Previous studies have shown that the majority of drugs used in sarcomas have not demonstrated substantial clinical benefit according to validated international scales. European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) and American Society for Medical Oncology (ASCO) Value Framework (AVF) are the most important scales. Little is known about the clinical benefits of guideline-recommended cancer drugs in GIST in routine practice. Here, we evaluate the clinical benefit of drugs recommended by NCCN in advanced GIST.
Methods
We reviewed publications between January 2002 and March 2023 that support recommendations of NCCN guideline version 1.2023 for GIST. We collected data regarding trial characteristics, efficacy, toxicity and quality of life (QoL). ESMO-MCBS and AVF were applied. Substantial clinical benefit was defined as a grade 4 or 5 (in a scale from 1 to 5) for ESMO-MCBS and a net health benefit (NHB) score ≥45 for AVF.
Results
We identified 16 recommended drugs or combinations in the GIST NCCN guidelines, 13 of them based on trials that included only GIST patients: 3 phase III randomized trials and 10 single arm trials (8 phase II and 2 phase I). Efficacy and toxicity data were reported in all trials but quality of life (QoL) was reported just in 2 (15,4%). ESMO-MCBS could be applied in all 13 trials. Nevertheless, AVF could only be applied in 3 (the 3 phase III trials). Only imatinib met the ESMO-MCBS substantial benefit threshold (4 points, one of them due to phase 4 experience). Ripretinib met the AVF threshold.
Table: 64P
Clinical benefit of drugs recommended by NCCN in advanced GIST
| Drug | Trial | ESMO-MCBS v1.1 form | EMSO-MCBS v1.1 score | AVF-NHB |
| Imatinib | Phase 2 | 3 | 4 (3+1) | - |
| Sunitinib | Phase 3 | 2B | 3 | 34 |
| Regorafenib | Phase 3 | 2B | 3 | 38 |
| Ripretinib | Phase 3 | 2B | 3 | 64 |
| Avapritinib | Phase 1 | 3 | 3 | - |
| Cabozantinib | Phase 2 | 3 | 1(2-1) | - |
| Dasatinib | Phase 2 | 3 | 1 | - |
| Sorafenib | Phase 2 | 3 | 1(2-1) | - |
| Nilotinib | Phase 2 | 3 | 1 | - |
| Pazopanib | Phase 2 | 3 | 1 | - |
| Everolimus+imatinib | Phase 1-2 | 3 | 1(2-1) | - |
| Ponatinib | Phase 2 | 3 | 1(2-1) | - |
| Imatinib+binimetinib | Phase 1b | 3 | 2 | - |
Conclusions
ESMO-MCBS could be applied in all trials supporting drugs used in advanced GIST but AVF just in a minority of them. Clinical benefit was only achieved by imatinib according to ESMO-MCBS and by ripretinib according to AVF. QoL should be analysed in future studies to determine real benefit according to these scales.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.