Table 1.
FDA approved systemic therapies for the management of advanced GIST
| Drug | N | Number of prior therapies (median) | Phase | Randomized | Other arm | RR | CBR | PFS (median) | OS (median) | Year | References |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Imatinib (first-line) | 147 | Any | II | Yes | 400 mg versus 600 mg daily | 53.7% (overall) | 81.6% (overall) | – | – | 2002 | [8] |
| 946 | Any | III | Yes | 400 mg daily versus 400 mg twice daily | 52% (overall) | 84% (overall) | – | – | 2004 | [10] | |
| 746 | Any | III | Yes | 400 mg daily versus 800 mg daily | 45% | 67–70% | 18 mo (400 mg daily) versus 20 mo (800 mg daily) | 55 mo (400 mg daily) versus 51 mo (800 mg daily) | 2008 | [11] | |
| Sunitinib (second-line; 50 mg daily × 28 days, 14 days break) | 312 | 1 | III | Yes (2:1 in favor of sunitinib arm) | Placebo | 7% (sunitinib) versus 0% (placebo) | 65% (sunitinib) versus 37% (placebo) | 27.3 wks (sunitinib) versus 6.4 wks (placebo) | – | 2006 | [13] |
| Sunitinib (second-line; 37.5 mg daily) | 60 | 1 | II | No | – | 13% | 53% | 34 weeks | 107 weeks | 2009 | [14] |
| Regorafenib (R) (third-line) | 199 | 2 | III | Yes (2:1 in favor of R arm) | Placebo | 4.5% (R) versus 1.5% (placebo) | 75.9% (R) versus 34.8% (placebo) | 4.8 mo (R) versus 0.9 mo | – | 2013 | [18] |
| Ripretinib (fourth-line) | 111 | At least 3 (imatinib, sunitinib and regorafenib) | III | Yes (2:1 favoring ripretinib) | Placebo | 9% (ripretinib) versus 0% (placebo) | 75% (ripretinib) versus 20% (placebo) | 6.3 mo (ripretinib) versus 1.0 mo (placebo) | – | 2020 | [21] |
| Avapritinib (PDGFRA D842V mutant − first line +) | 56 | Any | I | No | – | 88% | 98% | N/A | N/A | 2020 | [26] |
N, number of patients; RR, response rate; CBR, clinical benefit rate; wks, weeks; PFS, progression free survival; mo, month; vs, versus; N/A, not applicable; OS, overall survival; yr, year published; ref, reference; R, Regorafenib