One of the key points that has been established in first line treatment of advanced NSCLC is that two drug chemotherapy is superior to one drug chemo. Several trials from a decade ago showed that a two drug "platinum doublet" led to a longer overall survival than either a platinum alone (typically cisplatin at the time that these trials were performed) or another agent, such as paclitaxel alone. Starting in 2000, second line chemotherapy has also been shown to improve survival, originally with taxotere (docetaxel), later with alimta (pemetrexed) also being shown to produce essentially the same survival.

Since second line single agent chemo was tested and approved by the FDA, the next question was whether more is better. Would two drug chemo lead to better survival in the second line setting? Though there have been several trials that have tested this, none has been large enough to say anything definitive. But when multiple similarly designed trials are too small to say anything definitive, it can be helpful to pool the data from these trials to see if there is a clear signal as an aggregate experience.

Such a meta-analysis is just being published now, looking at the results from 6 trials that tested a single agent vs. a doublet. Most of these trials have shown the same clear trend that we see with three-drug combinations for first line therapy: a higher response rate and modestly longer progression-free survival, (PFS) but at the cost of markedly worse side effects and no real improvement in overall survival (OS). In the case of these second line trials, the response rate was 15.1% vs. 7.3% for doublet vs. singlet chemo, and the PFS was improved by 21% with the more intensive treatment, but that only translated to an absolute improvement in median PFS of about 2 weeks. Overall survival was essentially identical between the two approaches.

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In addition, this came at a cost of significantly greater frequently of moderate to severe hematologic (blood counts) and other side effects.

Finally, it's important to note that the median age of 61, nearly 10 years younger than the median age of newly diagnosed patients with lung cancer in the US today, and 90 percent had a good performance status. This was a relatively cherry-picked, unusually fit population, which should have favored a more aggressive approach. We can speculate that the "real world" patient population would be even less compelling for doublet chemotherapy.

There are a finite number of effective treatments in advanced NSCLC, and the real question is how best to distribute these agents and a patient's fitness for treatment over time. Most oncologists review these results and feel that it makes more sense to pursue an approach of sequential single agent treatments after the first line setting.