Metastatic pancreatic cancer: US approval for drug that doubles survival rates

In May, news of the exceptionally long standing ovation that greeted the results of the RASolute 302 Phase 3 trial at the American Society of Clinical Oncology (ASCO) conference had spread around the world. And now, in record time, the US Food and Drug Administration (FDA) has granted approval for daraxonrasib (Revolution Medicines Inc.), the ‘drug that extends the lives of patients with pancreatic cancer’, as several US newspapers have headlined.
Daraxonrasib, a RAS GTPase inhibitor, is the first targeted therapy to act on one of the key molecular mechanisms of pancreatic cancer: it ‘switches off’ the RAS oncogene, which for years was considered a ‘non-pharmacological’ target. The FDA has authorised its use for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have already received at least one course of chemotherapy and who are not eligible for systemic multi-agent chemotherapy.

The efficacy of this molecule was assessed in the RASolute 302 trial (a randomised, multicentre, open-label study) involving 500 patients, half of whom were treated with daraxonrasib and the other half with a standard chemotherapy regimen chosen by their treating oncologists. The study endpoints were overall survival (OS) and progression-free survival (PFS), assessed both in patients with a Ras mutation and in the general population. As an additional measure of efficacy, the ORR (Objective Response Rate) was calculated, i.e. the percentage of patients whose tumour shrinks or disappears completely following medical treatment.

The results of the study showed a statistically significant improvement in patients treated with daraxonrasib. In particular, the median survival in the overall population was 13.2 months, compared with 6.7 months for patients assigned to the standard chemotherapy group (representing a 60% increase in survival); PFS was 7.2 months in the experimental arm compared with 3.6 months in the chemotherapy group (a 51 per cent increase); an ORR of 30 per cent was also observed in the daraxonrasib-treated group, compared with 11 per cent in the control arm. The adverse effects of this drug mainly affect the skin and mucous membranes (stomatitis, oral disorders); gastrointestinal effects (diarrhoea and perforation) and pulmonary effects (interstitial lung disease/pneumonia) are rarer.

No drug had ever achieved these results before. That is why the results of the RASolute 302 trial, presented at the end of May at the ASCO conference in Chicago and published simultaneously in the New England Journal of Medicine, were met with a standing ovation and convinced the FDA to grant approval so quickly.

The medicine is taken by mouth (one 300 mg tablet a day) until the disease progresses or significant side effects occur.