Lung cancer

Checkpoint inhibitors show potential for first line use in NSCLC


Professor Karapetis

The next step for immune therapy in lung cancer is in combination with chemotherapy or radiotherapy as first line treatment, according to oncologist Associate Professor Chris Karapetis.

Immune checkpoint inhibitors are listed on the PBS as second line treatments for non-small cell lung cancer (NSCLC) but the latest trials show their potential for use first line in advanced  disease, Professor Karapetis, Senior Consultant Medical Oncologist at Flinders Medical Centre, Adelaide.

Speaking at the Australian Lung Cancer Conference (ALCC) 2018 in Sydney, Professor Karapetis said that following a negative result with nivolumab monotherapy in the CheckMate 26 trial and positive results with pembrolizumab monotherapy in the KEYNOTE 24 trial, combination approaches were now showing positive results in progression free survival (PFS) and overall survival.

Attention had recently focused on combinations of immune checkpoint inhibitors such as pembrolizumab and nivolumab with standard chemotherapy in patients with higher levels of  PD-L1 expression, who accounted for up to 30% of patients with NSCLC.

This had led to a change in practice in Australia, and the drug was now available through special access programs for patients with high levels of PDL1 expression, Professor Karapetis said.

Other strategies included using immune checkpoint inhibitors in combination with radiotherapy, which made the tumour release more antigen for the T-cells to act on.

“There’s a degree of priming that occurs when you subject a tumour to a treatment that effectively leads to cell death, antigen release and then the immune therapy comes on board on, so its effect may be enhanced,” he said.

Most recently there had been positive results with pembrolizumab in combination with chemotherapy for the first-line treatment of patients with NSCLC with significant improvements in both PFS and overall survival over chemo alone.

“We’re getting a consistent story. Once you see two or three drugs showing the same thing I think you can start to believe it, and it’s really interesting,” said Professor Karapetis.

“There certainly is a move towards exploiting these combinations, and exploiting the potential benefit of enabling antigen release and a greater immune therapy induced response against the tumour.”

Further positive results had been seen with combinations of two immune therapy drugs such as nivolumab and ipilimumab in the Checkmate 12 study, he added.

“The combined approach does produce an augmentation of anti-tumour response.”

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