Doubled survival in metastatic lung cancer with combination therapy

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Published: 25 Apr 2018
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Dr Leena Gandhi - NYU Langone Medical Center, New York, USA

Dr Gandhi speaks with ecancer at AACR 2018 about the outcomes of treating non-squamous non-small cell lung cancer with pembrolizumab and chemotherapy.

She discusses the response rates, overall survival and progression-free survival of 616 lung cancer patients whose tumours lacked EGFR or ALK mutations, 405 of whom received the trial combination.

These patients saw their overall risk of death reduced by 51%.

For more on these results, watch Dr Gandhi present the results to the conference in a press session.

We conducted a phase III global randomised placebo-controlled study of pembrolizumab in combination with pemetrexed and platinum as compared to pemetrexed and platinum alone in patients with metastatic non-small cell lung cancer who don’t have oncogenic drivers such as EGFR and ALK alterations for which there are specific targeted therapies. But it is the majority of the non-small cell lung cancer population. The study demonstrated a clear improvement in response rate, progression free survival and overall survival in the whole population as well as in all subgroups. There was no difference in overall survival benefit, really, in any subgroup although PD-L1 high expressing patients, so those with ≥ 50% expression had the greatest levels of benefit. Even those who had less than 1% expression had a survival benefit.
The study was a large phase III randomised placebo-controlled study conducted in sixteen countries at 126 different sites. Patients were randomised two to one to receive either pembrolizumab in combination with platinum and pemetrexed or platinum and pemetrexed alone with placebo. Following the platinum doublet therapy of four cycles patients went on to receive pemetrexed maintenance therapy either with placebo or pembrolizumab. Patients in the control arm could cross over to pembrolizumab monotherapy if they had confirmed progression on blinded independent review.

Were there any adverse effects?

Overall the adverse effects were really not different than what we might see with either chemotherapy alone or pembrolizumab alone. The incidence overall of chemotherapy side effects was really not changed and the incidence of immune mediated side effects was also not really different, with the possible exception of renal events. There was a slightly increased level of nephritis in the study in the combination arm, 1.7% compared to 0.4% with monotherapy, and overall there were more renal events with more acute kidney injury in the combination arm compared to the control arm. Although the number of serious adverse events was still low at 2%.
Do we need to see anything else before using this in clinical practice?
I don’t think that we necessarily need to see anything else before using it in clinical practice. In fact, this is already an approved regimen in the US and a few other countries on the basis of a phase II trial that predated this study. Most centres are doing standardised PD-L1 testing anyway to select patients for PD1 monotherapy and this could be implemented right away actually, pending regulatory approvals in other countries.

Anything else to add?

The only thing I wanted to add is that this study was presented in the context of other studies that were presented as well which demonstrated benefits to other combinations including other chemotherapy combinations and other immunotherapy combinations. So the challenge for us going forward is how to individualise patient care to select the right treatment for all patients. The one thing that has clearly changed is that the backbone of that care for all patients is immunotherapy instead of chemotherapy.