Can adding chemotherapy agents to gefitinib improve outcomes for advanced NSCLC?

This study investigated whether adding chemotherapy agents to gefitinib (Iressa) improved outcomes for patients with advanced non-small cell lung cancer (NSCLC). This study found that this combination improved survival but increased side effects for these patients.

The gene for epidermal growth factor receptor (EGFR) is often abnormal in NSCLC. The standard first-line treatment for EGFR mutant NCSLC is and EGFR-directed drug. While we have a target, treatment to give us long term remission (all cancer is gone) are still being investigated. The cancer usually becomes resistant to the treatments we currently have. 

pemetrexed (alimta) and carboplatin (paraplatin)

One such anti-EGFR drug is gefitinib. The addition of pemetrexed and carboplatin to gefitinib has shown promise in prolonging time without tumour growth. These are two chemotherapy agents. Alternating these therapies with gefitinib has also shown promise. The effect of combining all three agents on overall survival and time without tumour growth has not yet been compared to gefitinib alone. 

This study included 350 patients with EGFR positive NSCLC. Patients were assigned to one of two groups. The Gef group received gefitinib while the Gef+C Group received gefitinib with pemetrexed and carboplatin. The average follow-up time was 17 months. 

A radiologic response (change in tumour size seen on imaging or scanning) occurred in 75% and 63% of the Gef+C and Gef groups respectively.  The disease progressed in 99 and 138 patients in the Gef+C and Gef groups respectively. Those in the Gef+C group had a greater time without tumour growth or spread (16 months vs 8 months in Gef). Mortality or disease progression was 49% less likely in the Gef+C group.

Overall survival (OS) refers to the time from start of treatment to end of life. The OS was much longer in the Gef+C group with mortality 55% less likely than Gef. one patient in each group had mortality without any disease progression.

Significant toxicity occurred in 51% and 25% of the Gef+C and Gef groups respectively. These included immune suppression, kidney damage and potassium imbalances. Two fatal toxicities occurred in the Gef+C group and one in the Gef group.

It was concluded that adding pemetrexed and carboplatin to gefitinib improved survival but increased toxicity in patients with NSCLC.

This study was carried out at a single location. It mainly included non-smokers.

The toxicities seen may mean this treatment will not be recommended by your care team.