This randomized phase III trial compared TKI gefitinib alone versus combination treatment with carboplatin and pemetrexed (GCP) in the first-line in EGFR+ patients. Untreated patients with stage IIIB or IV non-squamous EGFR+ non-small cell lung cancer were randomized in a 1:1 fashion to receive either daily oral gefitinib alone or 4-6 cycles every 21 days of combination chemotherapy with carboplatin and pemetrexed PLUS daily oral gefitinib. Those in the gefitinib-only arm continued daily gefitinib until progression and were then intended to go on the same chemo regimen as those in the GCP arm. Those in the GCP arm followed the initial protocol and then moved to maintenance gefitinib and pemetrexed every 21 days.

This trial is significant in that it looks at a concurrent versus sequential approach to first-line treatment in a very specific population and whether there is any benefit to being more aggressive upfront. Results show a very impressive improvement in progression-free survival (PFS) in the combination arm over the gefitinib-only arm. PFS in the GCP arm was roughly 20.9 months compared with 11.2 months in the gefitinib-only arm. These differences were maintained over time in that there was a significant overall survival advantage in those treated with concurrent combination chemo plus TKI over those treated with TKI alone.

The results suggests that there could be a significant benefit to more aggressive treatment upfront which could change the course of the disease for a prolonged period of time. This study delineates the need for future phase III studies to clarify the benefit.The results of this trial, while impressive, will likely not change the standard of care in the U.S. at this time but clearly show the need for additional studies looking at whether there will also be a survival benefit of concurrent chemo plus third generation TKI’s such as osimertinib. View Dr. West’s Video.