Entry Detail
| General information | |
| Database: | DB00735 |
| Objective: | Most patients with non small cell lung cancer tumours that have EGFR mutations have deletion mutations in exon 19 or the Leu858Arg point mutation in exon 21, or both (ie, common mutations). however, a subset of patients (10%) with mutations in EGFR have tumours that harbour uncommon mutations. There is a paucity of data regarding the sensitivity of these tumours to EGFR inhibitors. Here they present data for the activity of afatinib in patients with advanced non small cell lung cancer that have tumours harbouring uncommon EGFR mutations. |
| Authors: | Yang JC, et al |
| Title: | Clinical activity of afatinib in patients with advanced non small cell lung cancer harbouring uncommon EGFR mutations: a combined posthoc analysis of LUXLung 2, LUXLung 3, and LUXLung 6. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 26051236 |
| Trial Design | |
| Clinical Trial Id: | NCT00525148, NCT00949650, and NCT01121393. |
| Agent: | afatinib |
| Target: | Receptor proteintyrosine kinase erbB2 Epidermal growth factor receptor |
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | posthoc analysis |
| Key Patients Feature: | tyrosine kinase inhibitornaive patients with EGFR mutationpositive advanced (stage IIIbIV) lung adenocarcinomas who were given afatinib in a single groupphase 2 trial (LUXLung 2), and randomisedphase 3 trials (LUXLung 3 and LUXLung 6). |
| Biomarker: | uncommon EGFR mutations |
| Biomark Analysis: | For the most frequent uncommon mutations, 14 (77.8%, 95% CI 52.493.6) patients with Gly719Xaa had an objective response, as did nine (56.3%, 29.980.2) with Leu861Gln, and eight (100.0%, 63.1100.0) with Ser768Ile. |
| Control Group Info: | Afatinib Versus Chemotherapy |
| Treatment Info: | Analyses were done in the intentiontotreat population, including all randomly assigned patients with uncommon EGFR mutations. The type of EGFR mutation (exon 19 deletion [del19], Leu858Arg point mutation in exon 21, or other) and ethnic origin (LUXLung 3 only; Asian vs nonAsian) were prespecified stratification factors in the randomised trials. they categorised all uncommon mutations as: point mutations or duplications in exons 1821 (group 1); denovo Thr790Met mutations in exon 20 alone or in combination with other mutations (group 2); or exon 20 insertions (group 3). they also assessed outcomes in patients with the most frequent uncommon mutations, Gly719Xaa, Leu861Gln, and Ser768Ile, alone or in combination with other mutations. Response was established by independent radiological review. |
| Primary End Point: | Clinical activity |
| Secondary End Point: | NA |
| Patients Number: | 600 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 71.1% in group 1, 14.3% in group 2 and 8.7% in group 3 |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 10.7 months (95% CI 5.6-14.7) in group 1, 2.9 months (1.2-8.3) in group 2; and 2.7 months (1.8-4.2) in group 3. |
| Median OS A vs. C: | 19.4 months (95% CI 16.4-26.9) in group 1, 14.9 months (8.1-24.9) in group 2, and 9.2 months (4.1-14.2) in group 3. |
| Adverse Event(agent arm): | NA |
| Conclusions: | Afatinib was active in non small cell lung cancer tumours that harboured certain types of uncommon EGFR mutations, especially Gly719Xaa, Leu861Gln, and Ser768Ile, but less active in other mutations types. Clinical benefit was lotheyr in patients with denovo Thr790Met and exon 20 insertion mutations. These data could help inform clinical decisions for patients with non small cell lung cancer harbouring uncommon EGFR mutations |