Phase 3 trials confirm benefits for immune therapies in NSCLC

Lung cancer

By Michael Woodhead

18 Apr 2018

Overall survival is doubled in patients with metastatic NSCLC  treated with pembrolizumab in combination with chemotherapy compared to chemo alone, a phase 3 trial has confirmed.

In findings released at the American Association for Cancer Research (AACR) annual meeting in Chicago, the KEYNOTE-189 study showed significant benefits for pembrolizumab combined with pemetrexed and a platinum-based drug in patients with advanced NSCLC and high rates of PD-L1 expression (50% or greater).

In the study, 616 patients without sensitising EGFR or ALK mutations who had received no previous treatment for metastatic disease were randomised to receive either 200 mg of pembrolizumab or placebo every three weeks for 4 cycles, in addition to chemotherapy. This was followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy.

After a median follow-up of 10.5 months, the estimated rates of overall survival (OS) at 12 months in the two treatment groups were 69.2% vs 49.4% (hazard ratio 0.49).

Progression-free survival (PFS) rates for pembrolizumab combination therapy versus chemotherapy were 8.8 vs 4.9 months (HR for disease progression or death, 0.52).

The survival benefit for pembrolizumab-combination therapy was seen across all categories of PD-L1 expression and at a cost of a low incidence of renal dysfunction, the researchers noted.  Adverse events of grade 3 or higher occurred in 67.2% of the patients in the pembrolizumab-combination group and in 65.8% of those in the placebo-combination group.

The study authors said the data from KEYNOTE-189 suggested that “introducing immunotherapy as a first-line therapy may have a favourable long-term effect on outcomes.”

In other late-breaking trial  results presented at the AACR meeting,  first-line treatment with nivolumab plus ipilimumab was shown to improve progression free survival compared to conventional chemotherapy among patients with NSCLC and a high tumour mutational burden.

In the Phase 3 CheckMate 227 study involving 139 patients treated with nivolumab plus ipilimumab the median progression-free survival versus chemotherapy (160 patients) was 7.2 versus 5.5 months (HR for disease progression or death, 0.58).

The results are published in the NEJM.

Pembrolizumab is already listed on the PBS for the treatment of unresectable Stage III or Stage IV malignant melanoma and from 1 May it will also be subsidised for patients with classical Hodgkin’s lymphoma.

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