Primary mutations in KIT and PDGFRA drive GIST in approximately 85% of cases, according to presenting author Prof. Margaret von Mehren (Fox Chase Cancer Center, USA) [1]. Ripretinib works as an inhibitor of KIT and PDGFRA.
The INVICTUS trial randomised patients to receive ripretinib at 150 mg daily (n=85) or placebo (n=44). The median age of patients was 60 years, with more aged 75 or more in the placebo group (9% for ripretinib vs 23% for placebo). Two-thirds of patients had received 3 prior therapies, and a third had received more than 4 (range, 4-7). The most common mutation was at KIT exon 11 (58%) followed by KIT exon 9 (16%).
In the study, the median PFS was 6.3 months with ripretinib compared with 1.0 months for placebo, amounting to a 85% reduction in the risk of progression or death (HR 0.15; 95% CI 0.09-0.25; P<0.0001). Additionally, the secondary endpoint of median overall survival was 15.1 for ripretinib vs 6.6 months for placebo (HR 0.36; 95% CI 0.20-0.63; P=0.0004), representing a 64% reduction in the risk of death. However, the hierarchical testing procedures utilised for the study prevented a conclusive establishment of statistical significance for OS.
The 6-month PFS rate was 51.0% (95% CI 39.4%-61.4%) for ripretinib compared with 3.2% for placebo (95% CI 0.2%-13.8%). PFS benefit was observed across all assessed patient subgroups. In those treated with 3 therapies, the HR for PFS was 0.15, in favour of ripretinib (95% CI 0.08-0.29). In those treated with ≥4 therapies, the HR was 0.24, also in favour of ripretinib (95% CI, 0.12-0.51).
"Ripretinib represents a potential new standard of care with broad activity in fourth-line GIST, a patient population with advanced refractory disease and no other approved options," said Prof. von Mehren.
- von Mehren M et al. ESMO Congress 2019. Abstract LBA87.
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Table of Contents: ESMO 2019
Featured articles
Interview with ESMO President Prof. Josep Tabernero
Breast Cancer
Triple negative breast cancer gets positive news: KEYNOTE-522 interim results
CDK4/6 inhibitors change landscape of breast cancer treatment: 2 studies
Veliparib-chemo combo prolongs survival without disease progression in some advanced breast cancer patients
Lung Cancer
Improved response rates without survival benefit with pembrolizumab in pretreated mesothelioma
Frontline ipilimumab/nivolumab improves OS in advanced NCLSC
First-line osimertinib significantly lengthens OS in NSCLC
Liquid biopsy to decide the best treatment for NSCLC
Melanoma
Long-term data from CheckMate 067
Adjuvant nivolumab provides benefit
Nivolumab+ipilimumab superior to monotherapy for melanoma brain metastases
GI Cancers
Preoperative chemotherapy for colon cancer
Nivolumab improves OS in advanced oesophageal cancer
Liquid biopsy identifies relapse in patients with colorectal cancer after surgery
In hepatocellular carcinoma, CheckMate 459 misses OS endpoint, but some interesting trends emerge
Heavily pre-treated GIST: ripretinib improves PFS
FGFR2+ cholangiocarcinoma: pemigatinib active as second-line treatment
IDH1+ cholangiocarcinoma: phase 3 results show improved PFS
Advanced colorectal cancer and BRAF mutations: triplet combination improves survival
Genitourinary Cancers
25% reduction in the risk of death in patients with nmCRPC treated with apalutamide
Enfortumab vedotin and pembrolizumab in advanced bladder cancer: initial results
PARP inhibition in selected patients slows progression on advanced prostate cancer
PFS extension with immunotherapy + chemotherapy in urothelial cancer
Third-line in mCRPC: CARD trial
Prostate cancer: spare radiotherapy after surgery
Novel mode of action for kidney cancer treatment
Gynaecological Cancers
Ovarian cancer patients benefit from combined maintenance therapy
Combination of PARP inhibition plus chemotherapy in ovarian cancer
PFS benefit with niraparib as first-line maintenance in ovarian cancer
CNS Tumours
Ceritinib in ALK+ NSCLC brain metastases
Solid Tumours/Pan-Tumour Data
Mixed data: AMG 510 in tumours with KRASG12C
DNA profiling of carcinoma of unknown primary should inform treatment
Larotrectinib: safe and effective in TRK fusion-positive tumours
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