UPDATED October 10, 2016 // COPENHAGEN — "It's a new day for lung cancer," commented Stefan Zimmermann, MD, from the University Hospital in Lausanne, Switzerland, after hearing the results from a landmark trial showing pembrolizumab (Keytruda, Merck) first-line beat standard chemotherapy in a certain population of patients with non-small cell lung cancer (NSCLC).
"For the first time, we will be offering immunotherapy first-line to our lung patients," Dr Zimmerman said. The landmark trial showed that pembrolizumab offers better efficacy and lower toxicity than chemotherapy.
"This study may change practice for the treatment of patients with advanced NSCLC. It is the first time a therapy has improved progression-free survival over the current standard first-line treatment with platinum-based doublet chemotherapy," commented Johan Vansteenkiste, MD, PhD, from University Hospitals, Leuven, Belgium.
Both experts were speaking here today at the 2016 European Society for Medical Oncology (ESMO) Congress, where the results were presented during a presidential session and simultaneously published in the New England Journal of Medicine.
The findings come from the phase 3 KEYNOTE-024 study, which was stopped early because of benefit, said lead investigator Martin Reck, MD, chief oncology physician, Lung Clinic, Grosshansdorf, Germany.
It was conducted in 305 patients with advanced NSCLC who hadn't yet received treatment and whose lung cancer biopsies showed no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations but high expression of programmed cell death ligand 1 (PD-L1) (≥ 50% of tumor cells).
In this patient population, pembrolizumab alone gave superior results to a platinum-containing doublet chemotherapy — median progression-free survival (PFS) was 10.3 vs 6 months (HR, 0.50), respectively.
The secondary endpoint of overall survival (OS) was also significantly improved with pembrolizumab. OS at 6 months was 80% vs 72% (HR, 0.60) and 1-year OS was 70% vs 54%.
The significant reduction in risk of death (by 40%) was "remarkable" as it was seen despite a high crossover rate (50%), Dr Reck commented, whereby patients in the chemotherapy group were given pembrolizumab on disease progression.
Pembrolizumab also showed a higher overall response rate (45% vs 28%) and a longer response duration (median not reached for pembrolizumab vs 6.3 months with chemotherapy).
Toxicity was lower with the immunotherapy compared with chemotherapy (grade 3/4 adverse events: 27% vs 53%), and the incidence of all adverse events was lower with immunotherapy.
The new data are likely to lead to approval of pembrolizumab as a first-line treatment for this particular group of patients (it is already approved for second-line use), and experts at the press conference agreed it should now be considered a new option in the first-line treatment of NSCLC. However, for patients with EGFR or ALK mutations (which together account for about 15% of NSCLC), targeted agents directed at these mutations remain the treatment of choice, they said.
The superior PFS and OS, along with the lower rate of treatment-related adverse events, suggest that pembrolizumab alone "may be the new standard of care for first-line therapy of PD-L1-expressing advanced NSCLC without treatable oncogenic aberrations," Dr Reck and colleagues concluded.
Discussing the results, Jean Charles Soria, MD, PhD, from Gustave Roussy Institute, Villejuif, France, agreed. "We have probably got a new standard of care," he said, but he questioned how many patients would be candidates. The researchers said that about 30% of NSCLC tumors show the PD-L1 expression of >50% was used as the cutoff in this trial, but this trial also excluded patients who had brain metastases and autoimmune conditions as well as those who were taking steroids, and so the patients who were in this trial probably represent only 10% of the patients seen in clinical practice, he said.
Dr Soria also touched on financial considerations – these new immunotherapies are expensive, but because they are better tolerated than chemotherapy, they do not require supportive care with erythropoietin and granulocyte–colony stimulating factors, which are given along with chemotherapy, and that is a saving.
Pembrolizumab Plus Chemo First-Line: New Data
Also presented during the presidential session was another trial of first-line pembrolizumab, but this time in combination with chemotherapy. These data come from the KEYNOTE-021 study, a smaller phase 2 trial in 123 patients, and while the data are very impressive, "we need to wait for phase 3 before we can move this combination into the clinic," Dr Zimmerman cautioned.
Thes results were presented by Corey Langer, MD, from the University of Pennsylvania, Philadelphia, and will be published online in the Lancet Oncology.
This study was conducted in patients with squamous NSCLC who were not selected based on PD-L1 expression, so it is a bigger patient population than the pembrolizumab-alone study, but again patients with EGFR and ALK mutations were excluded.
Pembrolizumab was added to the chemotherapy doublet of carboplatin plus pemetrexed (Alimta, Eli Lilly) and compared with chemotherapy.
The addition of pembrolizumab improved PFS by 13 vs 8.9 months (HR, 0.53; P = .0102), but also added to toxicity (grade ≥ 3 adverse events: 39% vs 26%). However, the discontinuation rate because of adverse events was similar (10% vs 13%), as were deaths considered treatment related (2 vs 3). The most common adverse events were fatigue (64% vs 40%), nausea (58% vs 44%), and anemia (32% vs 54%).
Dr Langer and colleagues concluded that the addition of pembrolizumab to chemotherapy resulted in a statistically significant and clinically relevant benefit, and the adverse events were manageable.
Both studies were funded by Merck (manufacturer of pembrolizumab). Dr Reck reports serving on advisory boards for Roche, Lilly, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. Disclosures for the coauthors are listed in the article.
European Society for Medical Oncology (ESMO) Congress. Abstracts LBA8_PR (pembrolizumab alone) LBA46-PR (pembrolizumab plus chemotherapy). Presented October 9, 2016.
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Cite this: Pembrolizumab First-Line Beats Chemo: 'It's a New Day for Lung Cancer' - Medscape - Oct 09, 2016.