The initial or "first line" management of advanced NSCLC has evolved quite a bit over the past 10 years, in that time moving from a much more uniform approach of very similar treatment for just about everyone to a revised approach that is far more individualized. First, we assess key issues like the subtype of NSCLC, focusing largely on whether it is squamous cell or non-squamous NSCLC, because treatment tends to diverge very early based on this factor. Second, a patient's performance status is another important issue, as patients who are frail often need a customized approach, because a more aggressive standard approach may be prohibitively difficult and even harmful. Third, a minority of patients (about 10% in North America and Europe, closer to 1/3 in Asia) will have a particular molecular marker, specifically a mutation in the epidermal growth factor receptor (EGFR), that is associated with a high probability of having a dramatic and long-lasting response to targeted therapy that inhibit the EGFR pathway. This particular activating mutation is most typically seen in never-smokers or people with a minimal, remote prior smoking history who also have an adenocarcinoma subtype of NSCLC.

Recommendations for first line therapy are most typically for a two drug chemotherapy combination, often with the drug Avastin (bevacizumab) -- a targeted therapy that blocks the blood supply to the cancer -- added for many patients who don't have squamous NSCLC. However, for patients with an EGFR mutation identified before they have started treatment, several recent studies have demonstrated that the rate of significant tumor shrinkage and the time before the cancer progresses are significantly longer with an oral agent that works as an EGFR inhibitor, such as Iressa (gefitinib) or Tarceva (erlotinib). Consequently, one of these agents is increasingly recognized as a very appealing first line treatment approach.

Elderly patients are often treated the same as younger patients if they have minimal limitations in their activity level. In contrast, frail patients are sometimes recommended to receive single agent chemotherapy rather than a multi-agent combination that may be prohibitively difficult to tolerate. The available evidence suggests that elderly and frail patients who have an EGFR mutation also typically have a very significant response to EGFR inhibitor therapy.

Further information is available through the following links:

Podcast on introduction to first line chemotherapy for advanced NSCLC

Podcast on personalization of first line therapy

Reference library summary on selecting optimal first line treatment for advanced NSCLC

Using molecular markers to guide treatment: The IPASS trial

Alimta (pemetrexed) benefit is histology-specific

Treatment approaches for first line therapy in frail patients with advanced NSCLC

Podcast discussion of managing advanced NSCLC in the frail and/or elderly

Iressa (gefitinib) for frail patients with an EGFR mutation