Treatment Strategies for EGFRm Non–Small Cell Lung Cancer With Visceral or Oligometastatic Disease

Summary of Treatment Strategies for Visceral and Oligometastatic EGFR-Mutated NSCLC

The approach to oligometastatic disease in EGFR-mutated non–small cell lung cancer requires careful definition and stratification of disease patterns. The ninth edition of lung cancer staging criteria now includes a new stage IV subdivision (M1c) for patients with a single extrapulmonary metastasis, such as 1 bone, brain, adrenal, or liver metastasis. However, oligometastatic disease encompasses both initial diagnosis scenarios and oligoprogressive disease, where patients develop limited sites of progression while on effective EGFR therapy. In oligoprogressive cases, the strategy typically involves continuing systemic EGFR therapy while adding stereotactic body radiation therapy to the progressing site, allowing patients to maintain their effective systemic treatment.

The definition of truly oligometastatic disease varies, often including 2 to 3 different sites rather than strictly single metastases. Clinical experience suggests that apparent single-site disease may reveal additional lesions after initiating EGFR therapy, particularly with bone metastases that can become sclerotic and appear as pseudo-progression at multiple sites, or liver metastases where additional lesions frequently develop over time. Brain metastases may represent more genuine single-site disease in EGFR-mutated lung cancer. The general approach involves starting systemic therapy first, then considering consolidative radiation to all initial tumor sites, including oligometastatic lesions.

Visceral metastases, particularly liver involvement, warrant special consideration, as they may indicate more aggressive tumor biology compared with the typical metastatic patterns of lung, lymph nodes, bone, and brain commonly seen in EGFR-mutated lung cancer. Unlike brain metastases, where FLAURA2 data showed significant benefit for combination therapy, liver and bone metastases did not demonstrate substantial differences in hazard ratios between combination and monotherapy approaches. However, patients with liver metastases may benefit from more aggressive up-front treatment given concerns about earlier progression, drawing from historical data showing subgroup benefits for combination approaches in liver metastatic disease. Close collaboration with radiation oncology remains essential for managing oligometastatic and oligoprogressive disease patterns.