Two clinical trials show promise with different targeted drugs for lung cancer

Lung cancer cell

Two drugs targeting different gene faults in lung cancer have shown potential to be better than those already available, according to unpublished clinical trials.

The drug alectinib (Alecensa), which targets a faulty version of the ALK gene, halted the growth of non-small cell lung cancers for 15 months longer than the standard treatment, a drug called crizotinib (Xalkori).

In a separate trial, the drug dacomitinib delayed the growth of tumours carrying a faulty EGFR gene for longer than the drug gefitinib (Iressa), one of the standard targeted medicines for lung cancers with faulty EGFR.

Both trials, presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (link is external) in Chicago, show how new drugs can be developed against already identified targets, potentially with added benefits. And some of the results could change clinical practice.

However, in the case of dacomitinib, this may come with more severe side effects, and experts cautioned that these drugs may not be suitable for some patients.

The phase III ALEX trial (link is external) included 303 patients with advanced non-small cell lung cancer. Their tumour cells carried a version of the ALK gene that’s fused to another gene, triggering uncontrolled cell growth.

Patients had not previously received treatment for their disease, and were then given either alectinib or crizotinib, which is the standard of care treatment.

The newer, more potent alectinib reduced the risk of the disease getting worse or death by 53%. This extended the average time before patients’ disease worsened from 10.4 months with crizotinib to 25.7 months with alectinib.

“This is the first global study to compare alectinib with crizotinib in ALK-positive lung cancer and establishes alectinib as the new standard of care for initial treatment in this setting,” said Dr Alice T. Shaw, Director of Thoracic Oncology at Massachusetts General Hospital Cancer Center in Boston in the US, who led the study.

“Nobody imagined it would be possible to delay advanced lung cancer progression by this much,” she added.

Dr Sanjay Popat, an expert in lung cancer at The Royal Marsden Hospital, said that the ALEX trial was “a major milestone in the treatment of this aggressive disease”.

“It changes the way we should treat our patients with ALK positive lung cancer, a small but important subset of all lung cancers,” he said.

Patients treated with alectinib experienced fewer side effects. And the drug was also better than crizotinib at preventing tumours from spreading to to the brain.

The second trial, called ARCHER (link is external), involved patients with a faulty version of the EGFR molecule inside their tumour cells.

“The second generation of these therapies is more effective, but can also cause greater side effects, so patients and their doctors will need to weigh the risks and benefits” - Dr John Heymach, ASCO Expert

452 patients were included on the phase III trial who had newly diagnosed, advanced stage non-small cell lung cancer. The patients were randomly selected to receive either dacomitinib or gefitinib, one of three drugs in routine use.

Patients who received dacomitinib had a 41% lower chance of their cancer getting worse or death than those treated with gefitinib. This meant the average time taken for their disease to get worse increased from 9.2 months with gefitinib to 14.7 months with dacomitinib. Longer follow up is needed to measure if this ultimately helps patients survive for longer.

“The front-line drug treatment for EGFR mutation positive lung cancer - an uncommon but important lung cancer subtype - has been hotly debated, with three highly effective drugs in routine use: erlotinib, gefitinib, and afatinib,” said Popat.

He added that while it seems that dacomitinib is more effective, this comes at a cost of increased side effects. This means that while dacomitinib offers a potential new treatment option, it might not be right for all patients.

“The second generation of these therapies is more effective, but can also cause greater side effects, so patients and their doctors will need to weigh the risks and benefits,” said ASCO Expert Dr John Heymach.