Although there has always been lattitude for individualizing treatment, I think developments in the last few years have added so many options that pretty much any standards we had from a few years ago have eroded. Particularly in a world in which the eligibility for avastin (bevacizumab) has is debatable (with growing experience of little risk when treating patients with brain mets, on coumadin, etc.), some less impressive results on the AVAiL trial with cis/gem +/- avastin, marginally positive results with erbitux (cetuximab), and a complete free-for-all in the transition from first line to second line (timing? maintenance?).
I thought it would be interesting to take the pulse on where the experts were, since my sense is that there's a lot of variability in how people are interpreting the data now. I sent an e-mail to about 30 expert colleagues from around the country and different institutions, with a simple thumbnail sketch of a fairly typical patient and asked specific questions of what treatment they would recommend as first line therapy, when they would stop it, and whether they would continue a maintenance therapy or switch to a new treatment, and if a new treatment, when. I also asked whether they would send any molecular markers. Here's the thumbnail sketch of the patient:
A never-smoking Caucasian 62 year-old woman has a cough, sees her MD, found after full workup to have a lung adenocarcinoma metastatic to lungs, liver, adrenals on PET/CT. Brain MRI shows multiple sub-centimeter asymptomatic brain mets without edema. She is referred to you for systemic therapy after seeing a rad onc, getting whole brain irradiation. Her PS remains good, kidney function fine, insurance would cover anything (this is something that can limit our treatment decisions). Summary: A healthy, motivated Caucasian woman with advanced adenocarcinoma of the lung, recently treated asymptomatic brain mets. And though I asked whether people would want to send for molecular markers, I limited responses to clinical variables, for the sake of argument I asked them to presume that there adequate tissue for this, and/or the patient refused another biopsy.
As I suspected, there wasn't an identical approach among the 24 responses I've received thus far when you look at the full range from first line to the start of second line therapy (so don't expect complete consensus even among the people who know all of the evidence). But I was surprised by a few signals I received:
1) A clear majority favored trying to send tissue for EGFR mutation status before starting treatment, although many said that they would wait on this. My presumption is that the IPASS trial results (described in a prior post), which showed unimpressive results with an EGFR inhibitor even in Asian never-smokers who didn't have an EGFR mutation, has now led many of us (myself included) to no longer rely on clinical variables as being "good enough".
2) In the absence of evidence of an EGFR mutation (including not having tissue available), only 4 patients recommended starting with tarceva (erlotinib). In fact, two of those fourspecified that they'd check a CT after just one month of tarceva, to make a quick switch in the face of early progression. The others recommended an approach with a cornerstone of platinum-doublet chemo.
3) I was surprised to see that so many experts recommended starting with alimta (pemetrexed) as the other half of a first line platinum-based doublet in 14 of the 20 respondents. Carbo won 9 to 4 over cisplatin to be paired with alimta. It's not that it was a bad choice, but just surprising to see this much consensus when so many doublets are relatively comparable. After a platinum/alimta combination, carbo/taxol received got 5 votes as the chemo backbone. The last vote was for cisplatin/gemcitabine.
4) It appears that people are getting increasingly comfortable with the concept of administering bevacizumab to patients with treated brain mets. Ten of 24 favored giving it first line, with chemo. None of the people starting with erlotinib suggested that they would give avastin with it.
5) In terms of duration of therapy, there were no real surprises. All of the folks giving tarceva would continue it until progression, while two thirds of those giving chemo would stop after four cycles of the doublet, and the other third after six cycles. I didn't offer an option of "4-6 depending on how the patient was tolerating it", but several people indicated that they were pretty neutral about 4 vs. 6 and would integrate tolerability and patient preference.
6) There was a lot more interest in maintenance therapy, as in continuing one or more agents from first line, than in switching immediately to a new second line therapy. Twelve of the people recommending chemo favored continuing either bev or pemetrexed or both. There were only a few stray votes for an immediate switch to a different chemo or erlotinib, and one who said they'd plan a switch from carbo/pem/bev x 6 cycles to erlotinib after a short break.
7) Erbitux never got a mention. It appears that nobody is awake at night worrying how to integrate it at this point.
Interestingly, the clear majority of people either recommended continuing tarceva until progression or one or more of the first line agents until progression. So even if the idea of immediate second line therapy isn't really catching on much yet, fewer and fewer patients are going off treatment entirely between first line and second line. And we're now thinking beyond a first line strategy, confident that our patients will do best by extending treatment beyond an initial 4-6 cycles of first line chemo.
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