REGISTRI Results Reported For First-line Regorafenib In KIT/PDGFR Wild-Type Metastatic GIST

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Patients with metastatic KIT/PDGFR wild-type gastrointestinal stromal tumours (GISTs) might derive some benefit from upfront treatment with the oral multikinase inhibitor regorafenib, suggests research reported at the ESMO Congress 2021. 

The REGISTRI study achieved a 12-week disease control rate (DCR) of 86.7% using a regorafenib dose of 160 mg/day that approached but did not meet the prespecified activity threshold of 90.0%, reported presenting author Javier Martin Broto, from Fundación Jimenez Diaz University Hospital in Madrid, Spain. 

However, he described the findings as “positive”, noting that the trial’s accrual was prematurely closed in December 2020 because of the COVID-19 pandemic after just 15 of the planned 20 patients had been recruited, potentially affecting the study’s results. 

The recruited patients were aged a median of 57 years, 53% were female and 33% had previously received imatinib therapy. Thirteen of the patients had metastatic disease and two had locally advanced, unresectable GIST. 

Succinate dehydrogenase (SDH) complex activity, a biomarker for GIST subtype, was preserved in 20%, deficient in 66% and not evaluable in 13%, Javier Martin Broto told delegates. 

The patients were given a median 7.8 cycles of regorafenib, during which time the safety profile was as “expected”, he said. More than half (53%) of patients required a dose reduction and 93% had a treatment interruption.  

The most common grade 3–4 toxicities were liver enzyme increases (20%), palmar–plantar erythrodysesthesia (13%) and skin disorders (13%), with anaemia, diarrhoea, hypertension and pruritus all occurring in 7% of patients. 

Central radiological assessment confirmed one partial response and 12 cases of stable disease, seven of whom had a reduction in tumour dimensions during treatment and seven a reduction in density. 

Over a median follow-up of 26 months, progression-free survival was a median 10.8 months, with 6- and 12-month rates of 65% and 33%, respectively. Two patients were continuing therapy and free from progression after 25 and 43 months, respectively. 

And median overall survival at this timepoint was 33.5 months, with nine patients still alive. 

Javier Martin Broto also reported that just 16 of the 30 individuals referred to the study on the basis of a locally assessed Sanger genotype result indicating KIT/PDGFR wild-type status had this status confirmed by central assessment using next-generation sequencing (NGS). 

“The high percentage of overlooked mutant GIST by Sanger raises the need of NGS in presumed KIT/PDGFR [wild-type] GIST”, the investigator said. 

Invited discussant Sebastian Bauer, from University Hospital Essen in Germany, praised the REGISTRI study as “a big achievement”, being the “largest series” of SDH-deficient GIST patients who have received regorafenib. 

While admitting that historical comparisons are “difficult”, he suggested that regorafenib is “probably” more active than imatinib but further analysis by patient SDH subtype is required.  

Sebastian Bauer added that the study “supports […] the current ESMO guidelines which suggest using regorafenib after sunitinib.” 

Reference  

1520O - Martin Broto J, Valverde C, Hindi N, et al. REGISTRI: Regorafenib in first-line of KIT/PDGFR wild type advanced GIST: A Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial. Ann Oncol 2021;32(suppl_5):S1111–S1128. doi:10.1016/annonc/annonc712