Combining Radiotherapy With a TKI Extends Survival in NSCLC

TOPLINE: 

Combining thoracic radiotherapy with first-line EGFR tyrosine kinase inhibitor (TKI) therapy improves progression-free survival by 6.5 months and overall survival by more than 8 months in patients with EGFR-mutated metastatic non–small cell lung cancer (NSCLC) and up to three metastatic organs. However, the combination is associated with a higher incidence of treatment-related adverse events compared with TKI therapy alone.

METHODOLOGY:

• EGFR-TKIs are the recommended first-line therapy option for patients with EGFR-mutated metastatic NSCLC; however, less than 40% of patients with metastatic disease receive local treatment, such as radiotherapy, and many experience intrathoracic disease progression.
• The current analysis explored whether adding thoracic radiotherapy to first-line EGFR-TKI therapy in patients with oligometastatic NSCLC improved survival.
• This multicenter phase 3 trial enrolled 118 patients who had EGFR-mutated NSCLC and up to 3 metastatic organs; patients were randomly assigned to receive icotinib, a first-generation TKI, alone or with thoracic radiotherapy (60 Gy in 30 daily fractions). Overall, 105 patients (89%) completed their allotted treatment.
• In both groups, 13.6% of patients had three metastatic organs; however, about 32% in the combination group and 44% in the TKI-only group had two, and 54.2% in the combination group and 42.4% in the TKI-only group had at least one. More than 40% of patients in each group — 40.7% in the combination arm and 42.4% in the icotinib arm — had brain metastases; most (71.4%) received brain radiotherapy.
• The primary endpoint was progression-free survival, and secondary endpoints included overall survival and treatment-related adverse events.

TAKEAWAY:

• The combination of thoracic radiotherapy and icotinib improved progression-free survival by 6.5 months compared with icotinib alone (median, 17.1 vs 10.6 months) and reduced the risk for progression by about 43% (hazard ratio [HR], 0.566; P = .004). Compared with the TKI-only group, the combination group led to significantly better local control (HR, 0.345) but not a significant difference in preventing distant metastasis.
• Radiotherapy plus icotinib also led to a significant improvement in overall survival (HR, 0.623), extending survival by a median of 8.2 months compared with the TKI-only group (median, 34.4 vs 26.2 months).
• Not surprisingly, patients without brain metastasis had better outcomes, with a median overall survival of 32.5 months vs 24.2 months. But, overall, adding thoracic radiotherapy to TKI therapy did not to significantly improve brain progression outcomes.
• Severe treatment-related adverse events were more frequent in the icotinib-plus–thoracic radiotherapy group (11.9% vs 5.1%), which included higher rates of grade 3 or 4 leukopenia (3.4% vs 1.7%) and neutropenia (3.4% vs 0%). Common treatment-related adverse events of any grade in the combination vs TKI-only group included skin rash (28.8% vs 35.6%), leukopenia (45.8% vs 18.6%), neutropenia (37.3% vs 11.9%), and diarrhea (13.6% vs 16.9%).

IN PRACTICE:

The findings suggest that ” the first-line TKI plus thoracic radiotherapy could significantly improve survival for patients with EGFR-mutated oligo-organ metastatic NSCLC than the TKI alone regimen,” the authors wrote. However, “the concurrent radiotherapy could bring more treatment-related adverse effects.” 

SOURCE:

The study, led by Hongfu Sun, MD, Shandong First Medical University, Shandong Academy of Medical Sciences in Jinan, China, was published online in Journal of Clinical Oncology.

LIMITATIONS: 

Using a first-generation EGFR-TKI, having a small patient population, and including patients with brain metastases may limit the generalizability of the findings.

DISCLOSURES:

The National Natural Science Foundation of China, the National Key Research and Development Program of China, Shandong First Medical University, and the Shandong Medical Association funded this work. One author received consulting fees and research funding from Hansoh Pharma.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.