New overall survival data of two phase III clinical trials, LUX-Lung 3 and LUX-Lung 6, demonstrated that patients with advanced non-small cell lung cancer whose tumors have the most common epidermal growth factor receptor mutation lived longer if treated with first-line afatinib compared to chemotherapy.
In the pooled analysis, afatinib (Gilotrif) prolonged survival of lung cancer patients whose tumors have common EGFR mutations compared with standard chemotherapy by a median of 3 months (27.3 to 24.3 months) and significantly reduced the risk of death by 19 percent (HR=0.81, p=0.037).
The most pronounced reduction in risk of death was 41 percent (HR=0.59, CI 0.45, 0.77), in patients whose tumors have the most common EGFR mutation, exon 19 deletion. For patients with the exon 21 (L8585R) mutation there was no impact on overall survival (HR=1.25, CI 0.92, 1.71). Exon 19 deletions occur with a frequency of approximately 48 percent in EGFR-mutant lung tumors.
The new data was presented June 2 at the annual meeting of the American Society of Clinical Oncology in Chicago. The analysis of the delay in tumor growth and adverse events associated with afatinib in comparison with standard chemotherapy were consistent with previously published results of the primary data from these two trials.
The LUX-Lung 3 trial compared afatinib with pemetrexed/cisplatin chemotherapy as a first-line treatment in patients with advanced NSCLC with EGFR mutations. LUX-Lung 6 clinical trial evaluated afatinib versus gemcitabine/cisplatin chemotherapy as a first-line treatment for Asian patients with advanced NSCLC with EGFR mutations.
Results from a third phase III study in NSCLC patients—LUX-Lung 5, which was also presented at ASCO—met its primary endpoint by showing an improvement in progression-free survival when continuing treatment with afatinib in combination with chemotherapy after the tumor started to grow on afatinib alone. This study compared afatinib and paclitaxel versus investigator’s choice of chemotherapy alone in patients with late-stage NSCLC whose disease has progressed after afatinib alone and have also failed several treatments, including chemotherapy, erlotinib or gefitinib.
Those patients who continued afatinib treatment, with the addition of chemotherapy, after progressing on afatinib alone, had a further delay in tumor growth compared to the group who stopped afatinib treatment and received chemotherapy only—tumor growth was delayed by 5.6 months and 2.8 months, respectively (p=0.003). This corresponded to a 40 percent reduction in risk of disease progression (HR=0.60).
Afatinib is an oral, once-daily kinase inhibitor, sponsored by Boehringer Ingelheim, and indicated for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 substitution mutations as detected by an FDA-approved test.
Cyramza-Docetaxel Combination Extends OS In Second-Line NSCLC
A phase III trial of Cyramza in combination with chemotherapy significantly improved overall survival in patients with second-line non-small cell lung cancer.
The global, randomized, double-blind trial compared Cyramza plus docetaxel to placebo plus docetaxel in NSCLC patients with progression after platinum-based chemotherapy for locally-advanced or metastatic disease.
The study included a total of 1,253 nonsquamous and squamous NSCLC patients from 26 countries on six continents. Overall survival was the trial’s primary endpoint and secondary endpoints included progression-free survival and objective response rate.
Patients treated on the Cyramza-docetaxel arm (n=628) achieved a median OS of 10.5 months compared to 9.1 months for patients on the placebo-docetaxel arm (n=625). The OS hazard ratio was 0.86 (95% CI, 0.751-0.979, p=0.023), which corresponds to a 14 percent reduction in risk of death.
Median PFS was 4.5 months in the Cyramza arm compared to 3.0 months in the placebo arm, with a PFS hazard ratio of 0.76 (p<0.001), which corresponds to a 24 percent reduction in risk of progression or death. Overall response rate was 23 percent with Cyramza and 14 percent on placebo (p<0.0001).
The study, named REVEL, was published in The Lancet and presented at the American Society of Clinical Oncology Annual Meeting June 2. REVEL is the first positive phase III study of a biologic in combination with chemotherapy to demonstrate improved overall survival compared to chemotherapy alone in second-line NSCLC.
“While there have been other recent phase III studies that have evaluated the addition of a cytotoxic or targeted agent in previously-treated NSCLC patient populations, none have demonstrated improved overall survival in the total patient population,” said Richard Gaynor, senior vice president of product development and medical affairs for Lilly Oncology, the drug’s sponsor.
“We are pleased that Cyramza demonstrated a significant survival improvement in a difficult-to-treat patient population where there continues to be a major unmet medical need in both nonsquamous and squamous NSCLC patients. [These data] also add to our growing clinical data set for Cyramza, which is being studied in multiple tumor types.”
Lilly intends to submit the first application of these data to regulatory authorities in the second half of 2014, according to the sponsor.
Cyramza as a single agent is approved for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma who have progressed after prior fluoropyrimidine- or platinum-containing chemotherapy. Cyramza is a VEGF Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2 and blocks binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D.
