primary or required resistance Gefitinib - 1266412

Hi Harald,

Welcome to GRACE. I'm sorry that your wife's diagnosis gives you a need to be here, but I'm heartened to hear that her current treatment regimen seems to be effective.

Oncologists use the results from clinical trials to guide treatment choices, but those results sum up what happens most often with a large group of patients. But each patient is different, and some patients respond contrary to the norm, for better or worse. In your wife's case, if the combination of Gefitinib and chemo is working, which is the better evidence - the median results of a large group of patients, or your wife's own response to treatment? Perhaps if you had used the Impress results to guide her treatment choice, you would have chosen a different path. But if it's working, it's hard to argue that you should shift gears.

In addition, as you point out, from the beginning at least some of her cancer did not respond to Gefitinib, so you'd be hard pressed to call that acquired resistance. Over the past few years it has become clear that not all patients' lung cancer consists of just a single type. Some cells may harbor an activating EGFR mutation, while others may not. If your doctor feels that Gefitinib was effective against at least part of her cancer, and the overall effect of the current regimen (including Gefitinib) is positive, perhaps part of that success is due to the targeted therapy. In that case, it may make sense to continue it.

Wishing your wife continued good luck with her treatments.

JimC
Forum moderator

My interpretation is a little different. Here, you have evidence that the cancer was not responding that well to Iressa (gefitinib) alone, actually with progression relatively early, and then you have evidence of a response after chemo is added. With that pattern, combined with the results from the IMPRESS trial that show no benefit in a well conducted study, it's fair to suspect that the gefitinib may be adding more toxicity than clear benefit.

I think it's very reasonable to take the approach that if things are going well, you don't need to make any changes, but the pattern I see is that the results are far better with the addition than you saw with gefitinib alone, and she didn't have a pronounced and prolonged benefit from EGFR inhibitor therapy, so I would be suspicious that the chemo is really doing the heavy lifting here.

Good luck.

-Dr. West

Dr. West,

I understand your analysis; there's always something new to learn. I guess I was swayed by the notation that after 5-1/2 weeks of Iressa (gefitinib) a CT showed response, and at 9 weeks the cancer in both the lung and bones was stable.

Of course from Harald's post we don't know how good the response was, which points out the difficulty of interpreting a patient's situation from a small amount of information rather than from the full information available to the patient's own medical team.

JimC
Forum moderator

It's absolutely an ambiguous situation, and I think on a panel of experts you'd have one or more advocating the "if it ain't broke, don't fix it" approach. You almost certainly wouldn't have complete consensus.

-Dr. West

It's possible to rechallenge with gefitinib or another EGFR TKI, but the effect is usually very transient, and the response rate tends to be under 10%. In particular, I would expect very little benefit in someone who received such a minimal benefit the first time around. Based on what we know and have available today, I think there is likely to be very little value in further EGFR-directed therapy in the absence of a detected T790M mutation and a novel EGFR inhibitor such as AZD9291 or CO-1686 (rocelitinib) as a new treatment approach. Gefitinib is not very consistently effective against brain metastases at standard daily dosing, so there really isn't any established role in taking it just for that purpose, especially in someone who has already developed resistance to it.

Good luck.

-Dr. West

Hello Harald,

I'm sorry for the delay in response. Following nsclc with blood tests aren't consistent at this time so CT scanning is still the gold standard in assessing whether or not there's significant enough change in the cancer to change treatments. As long as the CT scan remain stable lung cancer specialists would leave things as is.

Flares from discontinuing a TKI are not the norm but it is understood that they sometimes happen after a long time benefit from taking a TKI, such as a year or so. From your remarks above it doesn't appear your wife had anything close to that kind of benefit from Iressa so a flare wouldn't happen.

Sometimes a re challenge is tried after many months off a drug that previously good efficacy. It doesn't sound like that was the case for your wife.

I hope she does well on chemo.

All best
Janine

I really agree with Janine. Sending off blood tests looking for numbers of tumor cells and monitoring Ki-67 is not a remotely standard approach. I would not be inclined to either use these tests in the clinical management of lung cancer or modify treatments on the basis of it. There is no good evidence to support it, in contrast with the well-established approaches of following the disease status by a combination of imaging tests to look for measurable change and symptoms to assess a patient's clinical situation.

Good luck.

-Dr. West