Trial results for new lung cancer drug are ‘off the charts’, say doctors

Doctors are hailing “off the chart” trial results that show a new drug stopped lung cancer advancing for longer than any other treatment in medical history.

Lung cancer is the world’s leading cause of cancer death, accounting for about 1.8m deaths every year. Survival rates in those with advanced forms of the disease, where tumours have spread, are particularly poor.

More than half of patients (60%) diagnosed with advanced forms of lung cancer who took lorlatinib were still alive five years later with no progression in their disease, data presented at the world’s largest cancer conference showed. The rate was 8% in patients treated with a standard drug, the trial found.

The results are the longest progression-free survival (PFS) outcomes ever recorded in patients with non-small cell lung cancer, the world’s most common form of the disease. They were presented at the annual meeting of the American Society of Clinical Oncology (Asco) in Chicago on Friday.

“To our knowledge these results are unprecedented,” said the study’s lead author, Dr Benjamin Solomon, a medical oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia.

In the phase 3 trial, 296 patients with advanced forms of non-small cell lung cancer were randomly assigned to receive either lorlatinib (149 patients) or crizotinib (147 patients, of whom 142 ultimately received treatment).

Just over half of the patients were women. In about 25% of them their lung cancer had already spread to the brain when the study began.

The participants all had ALK-positive non-small cell lung cancer. Lorlatinib and crizotinib are both ALK tyrosine kinase inhibitors (TKIs). ALK TKIs are targeted treatments that bind to the ALK protein found in ALK-positive non-small cell lung cancer and stop the growth of tumour cells.

“Despite significant advancements with newer generation ALK TKIs, the majority of patients treated with second-generation ALK TKIs will have progression of their disease within three years,” said Solomon.

“Lorlatinib is the only ALK TKI that has reported five-year progression-free survival, and even after this time, the majority of patients continue to have their disease controlled, including control of disease in the brain.”

The five-year progression-free survival (PFS) rate was 60% in patients who took lorlatinib and 8% in the crizotinib group.

“You don’t need a magnifying glass to see the difference between these two drugs,” said Dr Julie Gralow, Asco’s chief medical officer. “Sixty per cent five-year progression-free survival in non-small cell lung cancer is just unheard of.”

Dr David Spigel, the chief scientific officer of the Sarah Cannon Research Institute in London, a world-leading clinical trials facility specialising in new therapies for cancer patients, welcomed the findings. “These long-term data results are off the chart,” he said.

Most of the patients experienced some side-effects. Treatment-related issues occurred in 77% of patients on lorlatinib and in 57% of patients on crizotinib. The most common side-effects reported in the trial that was funded by Pfizer were swelling, high cholesterol and elevated lipid levels.

Cancer Research UK’s chief clinician, Prof Charles Swanton, who was not involved with the study, said the “groundbreaking” results would offer fresh hope for patients with advanced lung cancer.

“Despite progress in our understanding of the disease, it can be incredibly challenging to control cancers that have spread and there are limited treatment options for lung cancer,” he said.

“Showcasing the power of cancer-growth blocker drugs, this study could present us with an effective way of stopping cancer in its tracks and preventing it from spreading to the brain.

“The groundbreaking results show that over half of the patients who took lorlatinib did not suffer a progression in their disease after five years. In contrast, over half of the patients who took crizotinib experienced disease progression after just nine months.

“Research like this is vital to find new ways to treat lung cancer and help more people survive for longer.”