Combining precision medicines can treat drug-resistant cancers

Launching a dual-pronged attack on tumours using a combination of two innovative precision medicines could treat patients with multiple common cancers, according to a clinical trial led by The Institute of Cancer Research (ICR) in the UK.

Published in the journal Cancer Discovery, the trial uses the genetically targeted drug olaparib — already licensed for ovarian, breast and prostate cancer — together with a promising new medicine, called capivasertib. The ICR played a key role in pioneering both of the two precision medicines in the combination — discovering how to genetically target olaparib and collaborating to create a precursor to capivasertib before the drug’s ultimate formulation by AstraZeneca.

In the phase I trial, ICR researchers and their collaborators gave 64 patients with advanced solid tumours — including those with breast cancer, ovarian cancer and prostate cancers — combinations of olaparib and capivasertib. The researchers used the drug combination to target two fundamental weaknesses in cancer at the same time — a damaged system for repairing DNA and ‘addiction’ to a molecule called AKT which fuels tumour growth.

The combination was well tolerated, and 25 of the 56 patients whose response could be assessed (45%) benefited from treatment, with their tumours either shrinking or stopping growing. Some of these patients had previously stopped responding to chemotherapy and other targeted treatments as their cancers became drug resistant, with many having mutations to genes involved in repairing DNA — including to the BRCA genes.

The findings thus provide early clinical evidence that olaparib and capivasertib have the potential to work well as a combination treatment and could improve outcomes for some patients with drug-resistant cancer. The team are now planning further, later-stage clinical trials to assess the drug combination’s benefit and to study its effect in patients whose tumours do not have faults in the AKT gene or related to DNA repair.

“Our study establishes the potential of a combination of two precision medicines for patients whose tumours have stopped responding to existing drugs,” said study leader Johann de Bono, Professor of Experimental Cancer Medicine at the ICR. “The combination of olaparib and capivasertib works by attacking two fundamental weaknesses in cancer, and could potentially be used to treat patients with several common tumours. I look forward to seeing the possible benefit of the combination tested in later-stage trials.”

Professor Paul Workman, Chief Executive of the ICR, added, “This new clinical trial is … an example of the pioneering strategy we have adopted at the ICR of targeting cancer evolution and drug resistance — often through the use of combination treatments to hit multiple targets at once and block off escape routes, just as is done with diseases like HIV.

“It’s very exciting to see two drugs pioneered thanks to the ICR’s research now being used together in patients, with the real possibility that they could offer an urgently needed new treatment option for patients whose cancers have become resistant to current treatments.”

Image credit: Jan Chlebik/ICR.

Please follow us and share on Twitter and Facebook. You can also subscribe for FREE to our weekly newsletters and bimonthly magazine.