Please Note: New Treatments Have Emerged Since this Original Post

One of the initial appeals of targeted therapies like tarceva (erlotinib) was that they may have fewer side effects and emerge as an alternative to standard chemo for some people. And one of the most appealing areas for offering a good alternative to standard chemo has been in the setting of older patients, who may be more wary of side effects and/or have additional medical problems than younger patients. A theme that has emerged very consistently in studies of elderly patients in lung cancer, and largely in oncology in general, is that fit older patients without many medical problems are very likely to do every bit as well as younger patients. Although studies of older patients with lung cancer have largely paired the elderly and "poor risk"/frailer patients (performance status of 2, corresponding to being symptomatic, a little limited in activities, but spending more than half of the day in bed or a chair) in pooled trials. More recently, though, we've come to recognize that these are overlapping but definititely distinct groups. We also learned in a prior post that unselected patients (not singled out by things like having never smoked, or having an EGFR mutation, for instance), with a marginal performance status who receive tarceva instead of standard chemo clearly do less well than patients who get standard chemo. But how well do older patients do with tarceva, independent of performance status? This is an important question now that more than half of all newly diagnosed lung cancer patients are over 70. A couple of trials help shape our thinking here.

The first is a trial done by David Jackman and colleagues at Dana Farber Cancer Center in Boston (abstract here), in which they enrolled 80 patients age 70 or older to receive tarceva at 150 mg as a first treatment, rather than after initial chemo. Although there were no rigid selection requirements, this appears to be at least a somewhat informally selected group, as only 7 patients had a squamous cell cancer (I'd suspect that the investigators were more likely to encourage this trial as a good option for patients with adenocarcinoma histology than squamous histology). They found a response rate of 10% (8/80 patients), with another 41% of patients demonstrating stable disease for at least two months. The median survival was about 11 months, and the one- and two-year survivals were 46% and 19%. While these numbers are a little better than we typically see with large trials in a general lung cancer population, it's not really comparing apples to apples, because we often see better results in smaller, single institution trials. Nevertheless, there's no suggestion that fit older patients on tarceva as a first line treatment did worse than you'd expect to see with chemo as a first treatment. As was seen in prior studies, the ones who developed a rash did better in terms of survival than older patients. Since Boston is also a place where they do a lot of work on EGFR mutations, they also checked for EGFR mutations and found that the patients with EGFR mutations did better than those who didn't. This may be because tarceva works far much better in patients with EGFR mutations, but there's also good evidence from other studies that the patients with EGFR mutations also do better overall than the patients without EGFR mutations, even if both groups get chemo and not tarceva or another EGFR inhibitor (having an EGFR mutation may be a prognostic factor of people just doing better no matter what). Here's a summary of survival by rash development and EGFR mutation status: Side effect rates were a little high for tarceva, with 79% of patients experiencing rash and 69% experiencing diarrhea. Four patients developed possible interstitial lung disease, an inflammation of the lungs from the tarceva, and one patient died from this complication. The second article (abstract here) that helps us is a retrospective analysis of the important NCI-Canada-led study of tarceva vs. placebo for second and third line patients that showed an overall survival benefit of a couple of months and led to its FDA approval in chemotherapy pre-treated patients (prior post on the subject here; abstract here). This trial enrolled 731 patients, and this paper compared the experience of the 163 patients 70 and older on the trial to see whether they received the same degree of benefit as the younger patients. In keeping with prior studies with chemo, the older patients received the same degree of benefit from tarceva vs. placebo in terms of median progression-free survival (3.1 vs. 2.0 mo), andmedian overall survival (7.6 vs. 5.6 months). This is despite the fact that the patients 70 and older had about twice the frequency of moderate to severe side effects as the younger ones (35% vs. 1% grade 3 or higher side effects, including rash, diarrhea, mouth sores, dehydration, fatigue, diminished appetite). They were also more likely to stop treatment altogether due to side effects (12% vs. 3%), and overall received less tarceva over time than the younger patients. To me, this is very reminiscent of the chemo evidence for older patients in the post-operative setting (prior post here), where older patients were more likely to experience side effects, stopped chemo earlier, but actually had every bit of the benefit and what appeared to be even more than in the younger patients. Overall, the evidence seems to demonstrate that while elderly patients may experience more side effects on tarceva, as is the situation with standard chemo, they certainly can benefit, with encouraging results for fit elderly patients getting it as a first line treatment for NSCLC, and also as a second or third line treatment where it's more routinely used and has FDA approval.