BERLIN—Adding the epidermal growth receptor factor (EGFR) blocker cetuximab to standard chemotherapy drugs significantly reduces the risk of death for advanced non-small lung cancer (NSCLC) patients–regardless of the platinum chemotherapy cocktail used.
That's the conclusion of a large meta-analysis presented here at the joint Congress of the European CanCer Organisation and European Society for Medical Oncology (ECCO15-ESMO34) by Jean-Louis Pujol, MD, PhD, Chairman of Thoracic Oncology at Montpelier Academic Hospital in France.
Last year, a Phase III study showed that adding cetuximab to vinorelbine/cisplatin chemotherapy significantly improves overall survival in patients with NSCLC (Pirker et al: JCO 2008;26(Suppl. 15): Abstract 3).
Three other randomized studies have demonstrated the improved efficacy of cetuximab added to different platinum doublets, compared with the platinum doublet alone: a Phase III study comparing carboplatin/docetaxel or carboplatin/paclitaxel, with or without cetuximab (Lynch et al: J Thorac Oncol 2008;3[Suppl 4]: S305), and two randomized Phase II studies investigating cisplatin/gemcitabine or carboplatin/ gemcitabine, and cisplatin/vinorelbine, with or without cetuximab (Butts et al: JCO 2007; 25:5777–5784, Rosell et al: Ann Oncol 2008; 19:362–369).
To confirm the robustness of the efficacy results and find out whether the choice of chemotherapy drugs mattered, Dr. Pujol and colleagues combined data from the four trials.
The pooled analysis, which included a total of 2,018 advanced NSCLC patients of all histological subtypes, showed that patients who received cetuximab had a 13% lower chance of dying within three years, compared with those who got chemotherapy alone.
Among other findings:
- Patients given chemotherapy alone survived a median of 9.4 months vs 10.3 months in the chemotherapy-plus-cetuximab group.
- Cetuximab was associated with a 10% improvement in progression-free survival time at three years.
- The overall response rate was 48% higher in the cetuximab group vs the chemotherapy-alone group.
All the differences were statistically significant, and the analyses were adjusted for study and patient age, sex, histology, tumor stage, and Eastern Cooperative Oncology Group (ECOG) performance status.
Subgroup analyses showed that patients with all histologic subgroup benefited, Dr. Pujol reported.
A heterogeneity test did not demonstrate a difference in treatment effect across the four studies, and three sensitivity analyses confirmed the primary analysis results for each endpoint.
The study was funded by a grant from Merck KGaA, which makes cetuximab.
New Therapies Needed
Despite the encouraging results, Dr. Pujol stressed the need for new therapies: “Fewer than 30% of patients with advanced non-small cell lung cancer respond to chemotherapy, so even though adding cetuximab increased the chance by another 48%, pushing the response rate up to about 45%, this shows that non-small cell lung cancer remains a disease that is very resistant to treatment,” he said.
Additionally needed are studies into whether the drug can help at early stages of the disease.
Cetuximab is currently approved for treating head and neck as well as for colorectal cancers.
Benefits of Meta-Analyses
“With these large numbers, we can be very confident that cetuximab adds to the benefits of chemotherapy,” said Chris Twelves, MD, Cochairman of the ECCO15- ESMO34 Program Committee and Professor of Clinical Cancer Pharmacology at Leeds Institute of Molecular Medicine in England.
“On the flip side, that benefit was only about four to five weeks, on average, and as of yet, we don't know how to pick out those patients likely to get greater benefit.”
Since the treatment can be costly, “the challenge now is to identify out the subset of patients who will get clinically meaningful benefit,” he said.
Dr. Twelves noted that in patients with colon cancer, KRAS mutation status predicts response to cetuximab—“But when we looked at its usefulness in lung cancer, that didn't hold true. The search for a molecular marker continues.”