As we established several years ago that it is indeed possible to do clinical trials with more than 50 or even 100 patients with advanced BAC, we were also seeing that those first forays into advanced BAC with standard chemotherapy were somewhat disappoingting (described further in another post). Fortunately, as it became clearer that we needed other options for advanced BAC, we started to see the first cases of patients with BAC who received Iressa on clinical trials who would sometimes have rapid and profound responses to this drug (before and after Iressa for 5 days):
BAC after 5 days of Iressa
A retrospective study from Memorial Sloan Kettering Cancer Center (MSKCC) reviewed the results from 139 patients who received the EGFR tyrosine kinase inhibitor (TKI) Iressa (gefitinib) as a single agent over a 5 year period and found that a diagnosis of BAC was among the strongest predictors for having a response to Iressa (abstract here).
I wrote and led the SWOG trial that we launched in 2001 to study Iressa at 500 mg daily in advanced BAC, and this is the largest prospective trial in advanced BAC that has ever been conducted (SWOG 0126 abstract here). This trial included two patient groups, one who had not received any chemotherapy and another previously treated with conventional chemotherapy; a total of 138 eligible patients were enrolled from around the US. We saw responses in about 1 in 6 patients, a bit more commonly in patients who hadn’t received any prior treatment. Nearly half of the patients at least didn’t have progression of their disease for several years. While the patient population as whole did about the same as we saw in the prior trial with taxol, several patient groups did better than others on the Iressa trial, including women, patients who developed a rash, never-smokers, and patients who were healthier to begin with Importantly, patients with pure BAC weren’t the only ones to do well with Iressa. Patients with tumors that were adenocarcinoma mixed with BAC did well, and patients with non-mucinous pure BAC did better than those with mucinous BAC.
A smaller trial, led by MSKCC, has treated approximately 100 patients with advanced BAC with Tarceva (erlotinib) at 150 mg daily. As in the SWOG trial, one quarter of the patients had been previously treated with chemotherapy. The results of this trial have only been published as an abstract thus far (preliminary results here), but approximately 24% exhibited a response, and those responses have lasted about a year on average. They also found a greater likelihood of response among lifelong non-smokers than former smokers or current smokers, and saw no responses were seen among patients who did not develop a rash on erlotinib. Responses were not restricted to patients with pure BAC and in fact were more commonly seen in tumors that demonstrated adenocarcinoma with BAC than in pure BAC.
Taken together, the evidence from these two trials clarify the utility of EGFR TKIs in the treatment of BAC, either in the front-line or salvage setting, although it appears that there remain distinct subsets that will benefit more or less from these agents. It is certainly reasonable to treat BAC with chemotherapy, with or without Avastin, as other types of NSCLC are managed, but EGFR TKIs are generally used early, either as first treatment or as a leading choice shortly thereafter.
Right now, I’m leading a trial through SWOG that gives patients with BAC the combination of Tarceva and the anti-angiogenenic agent Avastin (SWOG 0635), since the combination appears to be well tolerated and may be more active than Tarceva alone. Since BAC is generally treated with Tarceva now as an approach of choice, the question is whether we can improve on that with Avastin added, as adding Avastin to carboplatin/taxol has been shown to improve survival in non-squamous advanced NSCLC in general. Other interesting clinical trials of BAC are studying drugs like Alimta (pemetrexed), Velcade (bortezomib), Nexavar (sorafenib), Sutent (Sunitinib), and Erbitux(cetuximab). It is encouraging to see that the interest in BAC is steadily increasing in the lung cancer community, since this may lead to ongoing improvements in treatments for patients with BAC, as well as a better understanding of the disease.
posted by Dr. West @ 4:53 pm link to this post
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November 6th, 2006 at 2:50 pm
I just want to let you know that I’ve read your postings and I very much appreciate your research on behalf of BAC patients. Keep up the great work!
Dusty Donaldson
Diagnosed 9/2006 Stage 1B BAC
High Point, NC
dusty.donaldson@mba.wfu.edu
November 26th, 2006 at 10:13 pm
Thank You for posting on our Lung Cancer Site. Having someone who cares with your credentials, has been a boost to all of us who are fighting lung cancer, are or have cared for someone with this disease. My dad was Dx Feb 26/06 with NSCLC BAC and he past Sept 14/06.
As a nurse I am still stunned. There are so many questions that were not answered and as a family we are still confused. While some may have thought we were a family in denial, we were a family who were being told two different versions of what was happening to him. His oncologist, to the very end, said, “There may be some cancer cells there”
while the Pulmonolgist said
he is dying from BAC. When I saw his CT scan I was horrified. Total white out
on the right lung field. In 23 yrs as a nurse, I have never been so confused about anything more than this. It was suppose to be such a small area, that they said they got with 7 weeks of radiation, only to have him
be terminal one week after he completed his sessions.
Can you help us to understand what went so terribly wrong? Dad had copious amounts of frothy, white foam, nothing like I have ever seen or hope to ever see again, constantly
roll from his mouth 24/7. His oxygen levels were horrific. I don’t know if his lungs failed because of high levels of Prednisone after his radiation, to high levels of oxygen 10 liters
to maintain his sats or what. We need peace. We need someone to look at things and say, this is what I think happened with his lungs. He was 81, look 70, physically was in excellent health his entire life, was active, ate great, did the treadmill without fail daily, etc. It is shocking to think that he had no lung volume…none. Please, if you can help answer my questions, let me know.
Note: He hemorrhaged during his Bronchoscopy
He was Dx at this time with
:end stage Emphasema, yet, this is someone who exercised regulary and never was short of breath until he got Pneumonia in Jan. 06.
He was told at the time he had 1 Liter of Lung Volume after his Pulmonary Function Test and after his Bronch wa
on 02 3-5 liters constantly.
His PET/MRI were negative for mets. We were told there might possibly be one
lymph node light up, but, that wasn’t even clear.
We were told this was slow growing and he could have three to five yrs. One oncologist suggested radiatin and chemo. We sent him to a Lung Cancer Treatment Center for a 2nd opinion and they said with his age, low lung volume and etc. Tarceva is what they would advise. He took the gamble and went with the radiation. He had absolutely no air. It was the most horrible thing to watch and I just need help to understand what went wrong. His left lung looked totally black on the CT scan. How can it look so good and he have only one liter of lung volume and no air, even on oxygen? Why couldn’t the left lung carry him if it didn’t have emphysema? We need someone who can look at things and help us to put closure to this. Dad was such a wonderful person and a devoted husband and father that it has crushed us to know he went through virtual hell and we aren’t sure what exactly went wrong so fast.
I have read your other posts and we are so happy you are online with us. Respectfully, jolene
jolenehinrichs@hotmail.com
November 26th, 2006 at 10:19 pm
Dr. West
I apologize for such a long post. I just got home from a long shift and my post demonstrates that I obviously have OCD where my dad is concerned. Sorry. Jolene
December 9th, 2006 at 4:11 pm
[…] I have already reviewed (in a post here) the activity of both iressa and tarceva in advanced BAC, where EGFR inhibitor therapy is generally used early in treatment, either before chemo or after one line of chemo. In the main trials of advanced BAC, iressa and tarceva have a response rate in the 15-25% range, and many of these are very prolonged responses. Another trial (Lee and colleagues paper here), clinically selecting based on never-smoking status, gave iressa to 37 previously untreated patients in Korea. In keeping with the usual findings for the never-smoking population with lung cancer, the patients on the trial were primarily women (92%, in fact), and all of the patients had adenocarcinomas or adeno/BAC mix. The response rate in this group was 69% (!), and the median time until progression was about 7.5 months, with an estimated one year survival of 73%. Interestingly, 7 of the 10 patients with brain metastases had shrinkage while on iressa. Also, while we have often thought of BAC as being particularly responsive to EGFR inhibitors, the response rate was actually higher among the patients with adenocarcinomas that were not mixed with BAC (76% vs. 43%). […]