France Weighs in on EGFR Inhibitor Therapy for BAC; Mucinous vs. Non-Mucinous BAC

H. Jack West, MD, Founder, President and CEO

I reviewed a couple of presentations on bronchioloalveolar carcinoma (BAC) at ASCO 2007, including one by Cadranal and colleagues in which patients with advanced BAC received single agent Iressa (abstract here). This study enrolled 88 eligible previously untreated patients with advanced BAC or adenocarcinoma with BAC features, about 55% women/45% men (typical for BAC trials to have slightly more women than men, unlike other types of lung cancer) to receive Iressa at 250 mg daily. They did a repeat CT scan three months after starting Iressa and looked at the disease control rate (DCR), the combination of responses and stable disease, in patients at that point. The response rate of 13% and disease control rate of 29% were just a little lower than other trials of EGFR inhibitors in BAC (one of Iressa at 500 mg daily in the US that I led (abstract here), and another of Tarceva at 150 mg daily that was led by Drs. Vince Miller and Mark Kris at Memorial Sloan Kettering (abstract here). While the French group didn't report a median survival, they did report a one-year survival of 52% that was right in line with my earlier US-based study, so it didn't appear that a lower dose of Iressa was associated with a worse outcome. Here are the available efficacy results for the three similar trials, side by side:

IFCT vs other EGFR TKI trials in BAC table (Click to enlarge)

As we've seen as a recurring theme, in all of these trials women did somewhat better than men, never-smokers did better than former or current smokers, and the people who developed a rash also did better than the ones who didn't develop skin toxicity.

One way in which the French study moved things along in the world of BAC was by noting differences in outcome between the half of patients with mucinous BAC vs. those with non-mucinous BAC, among the 65 who had tissue available for study. They found that the folks who had non-mucinous BAC did considerably better on the Iressa trial than those with mucinous BAC:

IFCT mucinous vs. Non-mucinous BAC on gefitinib

That would perhaps just be an interesting curiosity, except that we saw the same significant difference, with significantly better results with Iressa in the patients on our SWOG trial who had non-mucinous instead of mucinous BAC (reported in a separate abstract here):

SWOG 0126 mucinous vs. non-mucinous BAC

We haven't seen any analysis like this yet from the Memorial Sloan Kettering trial with tarceva, but with the two trials that have looked at this issue showing the same exact finding, it does seem that Iressa, at least (and I'd suspect it's the same with Tarceva) is particularly helpful with the non-mucinous form of BAC. Interestingly, the small study of taxol (infused slowly over four days; abstract here) actually showed that the responses were in patients with mucinous BAC, and that there were no responders with non-mucinous BAC, although the actual number of patients who had tumor tissue available for analysis was very small. This remains an open question, but it's possible that mucinous BAC may be more responsive to chemo and that non-mucinous BAC is more responsive to the EGFR inhibitors like iressa and tarceva.

We'll be studying this a lot more in the future, but at this point we might actually want to begin to subdivide BAC into different groups to see if we can refine best treatment plans by whether patients have the mucinous or non-mucinous subtype. They appear to actually be somewhat different diseases.


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