The incidence of metastatic bone disease or brain metastasis was not different between EGFR mutated, KRAS mutated and KRAS/EGFR wild type (wt) patients in small, retrospective study performed by Dutch investigators. Time from diagnosis of metastatic non-small cell lung cancer (NSCLC) to development of metastatic bone disease, first skeletal-related event or brain metastasis and post-brain metastasis survival did not differ. However, survival after diagnosis of metastatic bone disease was longer in EGFR mutated patients. The results were presented by Dr Lizza Hendriks of the Department of Respiratory Medicine, Maastricht University Medical Centre in Maastricht, Netherlands at the European Multidisciplinary Conference in Thoracic Oncology (EMCTO), held 9-11 May, 2013 in Lugano, Switzerland.
Patients with metastatic NSCLC often progress by developing bone and brain metastasis. It is controversial whether NSCLC patients develop brain metastasis more frequently or have differing outcomes, including survival following brain metastasis diagnosis according to the underlying genetics of their tumours. Some reports suggest that patients with EGFR mutations are more likely to develop brain metastasis and have longer survival after brain metastasis diagnosis than wt or KRAS mutated patients, but other reports are inconclusive. As yet, there are no similar data for NSCLC patients who develop metastatic bone disease, leading Dutch investigators to conduct a retrospective matched control study comparing the time from metastatic NSCLC diagnosis to the development of metastatic bone disease or brain metastasis, symptoms, skeletal-related events and subsequent survival in EGFR mutated, KRAS mutated and wt patients.
The presented findings concern analysis of all EGFR mutated patients diagnosed with metastatic NSCLC between October 2008 and December 2011 at study researchers’ molecular laboratory, which includes five referral hospitals. Each EGFR mutated patient was paired with a consecutive patient who was KRAS mutated or wt metastatic NSCLC. Patients who experienced another malignancy within two years of diagnosis of metastatic NSCLC or who had no follow-up were excluded from this study. Data regarding age, gender, histology, WHO performance status, treatment, diagnosis of bone and brain metastasis, skeletal-related events and survival following diagnosis of metastatic bone disease/brain metastasis were collected and analysed.
Data from 130 patients were included; 42 (32.3%) patients with EGFR mutations, 48 (36.9%) with KRAS mutations and 40 (30.8%) wt patients. The incidence of bone and brain metastasis at initial presentation did not differ, as well as patterns of time to diagnosis of metastatic bone disease in genetically defined groups. At the time of diagnosis of metastatic NSCLC 70% of patients had already bone metastasis. Median time to metastatic bone disease was 8.4 months in EGFR mutated patients compared with 27.5 months in KRAS mutated patients and 9.3 months in wt patients (p=0.81). The EGFR mutated cohort achieved a longer survival post metastatic bone disease diagnosis, 15.5 months compared with 9.4 and 2.8 months, respectively, for KRAS mutated and wt patients (p=0.001). Time to first skeletal-related event was 3.5, 7.3 and 4.7 months respectively (p=0.82).
At the time of diagnosis of metastatic NSCLC, 38% of patients already had brain metastasis. The time to brain metastasis did not differ significantly between the three groups in this study and was 12.3, 9.1 and 11.6 months, respectively. Survival post brain metastasis was 5.6, 8.9, and 4.6 months, respectively, in EGFR mutated, KRAS mutated and wt patients (p=0.57).
The authors concluded that incidence of metastatic bone disease or brain metastasis was not different between EGFR mutated, KRAS mutated and wt patients. The time from diagnosis of metastatic NSCLC to developing bone metastasis, first skeletal-related event or brain-metastasis and post-brain metastasis survival did not differ in this study. However, survival after metastatic bone disease was significantly longer in EGFR mutated patients. The authors pointed out the importance of prevention and treatment of skeletal-related events in these patients.
The study discussant, Dr Benjamin Besse, congratulated to the study team. This is the second study that compared molecular profile and metastatic pattern, however due to small subgroups, it is hard to conclude on survival and treatment's benefit. Wild type subgroup is heterogeneous (ALK, RET, ROS.). He speculated on study potential implications in term of modified work-up for metastatic patients and different follow-up for resected patients. Commenting on results in the cohort of patients with brain metastases, Dr Besse said that EGFR mutated NSCLC patients are maybe undertreated when brain metastases occur or it could be that slow progression influence on delay of the whole brain radiotherapy. In the small cohort of patients with bone metastases, he speculated that wild type patients may be undertreated and additionally bisphosphonates have been poorly prescribed.
EMCTO is organised in partnership between the European Society for Medical Oncology (ESMO), The European Society for Radiotherapy and Oncology (ESTRO), the European Society of Thoracic Surgeons (ESTS) and the European Respiratory Society (ERS), and the European Thoracic Oncology Platform (ETOP). The five partners have created a programme that integrated perspectives from the different disciplines and demonstrated how the multidisciplinary team can combine knowledge for personalised treatment of the whole range of thoracic oncology tumours.
All authors have declared no conflicts of interest.