Should chemotherapy be used with EGFR-TKIs as a first-line treatment for advanced NSCLC?

This review was carried out to analyze the effectiveness and safety of EGFR tyrosine kinase inhibitors (TKIs) plus chemotherapy (CT) versus EGFR-TKIs alone as a treatment for advanced non-small-cell lung cancer (NSCLC) that is EGFR-positive. The authors found that EGFR-TKIs and CT treatment improved survival for these patients while increasing side effects.

Lung cancer is one of the leading causes of cancer-related death worldwide. NSCLC is responsible for 85% of all lung cancer diagnoses. Lung cancer is usually diagnosed at a late stage which makes treatment difficult at times. 

EGFR-positive cancer cells have a genetic abnormality that causes excess growth of cancer cells, in particular lung cancer cells. EGFR TKIs such as erlotinib (Tarceva) or gefitinib (Iressa) are a targeted therapy that attacks this genetic abnormality. EGFR-TKIs are currently used alone as a treatment for EGFR-positive advanced NSCLC. However, in time, patients become resistant to this therapy.

Previous trials have suggested that treatment with CT and EGFR-TKIs improves the resistance to this targeted therapy. However, the results regarding survival were contradictory in other studies. Therefore, whether EGFR-TKIs alone or in combination with CT improve the outcomes of patients with advanced NSCLC that is EGFR-positive is still not clear. 

The authors of this study analyzed 8 clinical trials that involved 1349 patients with EGFR-positive advanced NSCLC. All patients in the trial received a TKI as first-line treatment. 704 patients also received CT.

Patients in the CT plus EGFR-TKI combination group had a 44% higher chance of longer survival without cancer worsening compared to EGFR-TKIs alone. 2 CT drugs and CT given at the same time as EGFR therapy were associated with longer survival without cancer worsening compared to one CT drug or CT given after EGFR therapy.

Patients in the EGFR-TKI and CT combination group also had a 30% higher chance of survival overall compared to EGFR therapy alone. 

The addition of CT to EGFR-TKI therapy resulted in a higher risk of side effects compared to EGFR-TKI therapy alone. The side effects that were more common in the combination group were low blood cell counts, tiredness, loss of appetite, nausea, vomiting, and diarrhea.  

The authors found that combining CT with EGFR-TKIs improved the survival of patients with EGFR-positive advanced NSCLC while increasing the risk of side effects.

The studies analyzed had different protocols which made comparisons more difficult. The treatment drugs were different among studies. Also, some of the data might have been missing. This might have influenced the results.