New Oral Drug Daraxonrasib Doubles Survival in Advanced Pancreatic Cancer

A new experimental once-a-day pill has shown encouraging results against pancreatic cancer, which is among the deadliest and hardest-to-treat forms of the disease. The findings were shared at the annual meeting of the American Society of Clinical Oncology (ASCO).

The drug, called daraxonrasib, was tested in a large international trial on patients with advanced pancreatic cancer whose disease had worsened despite earlier treatment. In these patients, the oral drug nearly doubled the average survival time. According to Professor Anant Ramaswamy of the Tata Memorial Centre, Mumbai, the median survival for advanced pancreatic cancer has stayed close to one year for decades, rising only from about six months in the late 1990s to roughly nine to twelve months three decades later. Against that slow progress, an oral pill that doubles survival in pre-treated patients is considered a major step forward.

How the drug works

Daraxonrasib targets a cancer-driving gene mutation called KRAS. The RAS family of genes makes a protein found in almost all cells of the body. When the KRAS gene is mutated, it stays permanently switched 'ON', which disturbs normal cell activity and lets cells grow without control, turning them cancerous. About 80 per cent of pancreatic cancers carry changes in the KRAS gene, and RAS-family mutations are seen in roughly 20 per cent of all cancers. Daraxonrasib works from inside the cell to block this overactive state and shut down the pathways that feed cancer growth. Doctors describe it as the first drug of its class able to suppress RAS activity across its different subtypes, whether the gene is mutated or not.

Why pancreatic cancer is so hard to treat

Several factors make this cancer difficult. Most patients, between 70 and 90 per cent, are diagnosed only at an advanced stage. Targeted drugs and immunotherapy that have helped in many other cancers have so far shown little effect here. In addition, both the tumour and the surrounding supporting tissue, known as the stroma, tend to resist available treatments.

Side-effects and who can benefit

Even though it is taken as a pill, daraxonrasib caused side-effects at a level close to chemotherapy, against which it was compared. Reported effects included skin rash, loose motions, mouth ulcers, vomiting, tiredness and a drop in haemoglobin levels. About one-third of patients needed their dose reduced. For now, the patients considered suitable are those with pancreatic cancer who have already received chemotherapy and whose disease is getting worse. Trials are also studying the drug in patients who have not yet received any treatment.

Wider use and availability in India

Because RAS mutations appear in about a fifth of all cancers, daraxonrasib and similar drugs are being tested in other cancers too, especially lung and colon cancers, which are common and often carry RAS mutations. The drug is not yet available in India, but experts expect this class of drugs to reach the country given its potential. Doctors note that demand is already high, with long waiting lists even to join clinical trials of RAS inhibitors. The development is seen as a notable advance for precision medicine, the approach of matching treatment to the specific genetic features of a patient's cancer, though experts stress that surgery, chemotherapy and radiotherapy remain the basics of cancer care.