There’s a new post at the GRACE website on the topic of whether oncologists should do molecular testing routinely for NSCLC tumors.  This is the subject of a debate in which I’ll be participating in an upcoming meeting.  You can read more about the topic here.

  Dr. Laskin wrote a new post on the GRACE site, here, describing in some detail the negative ESCAPE trial of sorafenib with chemo for first line treatment of advanced NSCLC.

  Although we’re mothballing the OncTalk site and not really adding to it, some people have noted that GRACE doesn’t yet offer a way to get alerts when new posts are written.  That feature is in the works.  In the meantime, I can write a brief note here that triggers an alert until we have the proper mechanism in place.

  The second post of the article on tarceva for advanced BAC, based on a clinical trial from Memorial Sloan Kettering Cancer Center, focuses on biomarkers correlated with better and worse results with tarceva.  This post is available here on the GRACE website.

   I wrote a new post summarizing an interesting trial of tarceva (erlotinib) in bronchioloalveolar carcinoma, or BAC.  It’s available on the GRACE website, here.

  There is a new post on the GRACE website, available here, on the topic of tumor cavitation and potential risk during treatment with anti-angiogenic drugs for lung cancer.

   Because the anti-angiogenic drug avastin (bevacizumab) has been associated with some degree of increased risk of bleeding since the beginning of its development in lung cancer, the key trials have historically excluded patients who have been on blood thinners, at least at the standard dose (full dose anti-coagulation, or FDAC).  In fact, though, patients with colon cancer have historically not been restricted, so the question has really been whether it’s necessary to restrict NSCLC patients who need FDAC from receiving avastin.  In the US-based ECOG 4599 trial that compared chemo (carbo/taxol) alone to chemo/avastin and led to avastin’s approval (abstract here), patients who developed a blood clot that required blood thinners were taken off of the study.  But is that necessary?

   The bit of evidence we have about FDAC and avastin comes from the AVAiL trial done in Europe that compared chemo (in this case, cisplatin/gemcitabine) and placebo to the same chemo with either low dose or high/standard dose avastin.  While patients on the AVAiL trial were not eligible if they were already on FDAC before the trial, the study did allow patients who developed a blood clot while on treatment to stay on the trial after initiating blood thinners.  This gave an opportunity to compare the rates of bleeding complications among the patients not on FDAC to those who started FDAC and continued with avastin.

   Developing blood clots is pretty common among patients with cancer, especially those with adenocarcinomas, who were the clear majority of patients on this trial that also excluded patients with squamous cancers.  A total of 86 patients, divided pretty evenly among placebo arm, low dose, and higher dose avastin, were followed on while on FDAC along with their treamtent.  They were compared to 900 other patients who remained off FDAC.  As presented by Natasha Leighl from Toronto (reference here), there were no serious or fatal pulmonary hemorrhage events (coughing up blood) in patients on FDAC while also on avastin; there was a higher risk of bleeding in all patients on FDAC, including those who received placebo instead of avastin, but the real excess of bleeding events were just the mild grade 1 episodes like slight blood streaking with a cough, or a bloody nose. 

   Other studies are beginning to look at blood thinners with avastin and other antiangiogenic drugs, and at this point it’s really to early to declare it safe to give them together, but there also isn’t a clear signal of a significantly increased risk of bleeding, at least not beyond the risk of bleeding we see in patients on blood thinners overall.  I’ll update with any new information if we see more study results presented at the ASCO meeting in early June. 

  For those of you who are interested in the screening controversy over detecting early stage lung cancer, there’s an editorial in yestreday’s New York Times.  I found it to be a balanced discussion, covering the highlights of both the promise and potential problems of screening.  The link is here.

   Please read the new post on a new trial with erbitux showing a survival benefit in lung cancer here.  The full post is on the GRACE website.

   We got some big news in the form of a press release today: avastin (bevacizumab) didn’t produce a survival benefit in the European AVAiL (AVAstin in Lung Cancer) trial of cisplatin/gemcitabine with or without avastin at either a higher dose (15 mg/kg IV every three weeks) or a lower dose (7.5 mg/kg IV every three weeks):

(Click on image to enlarge) (more…)

   Since the anti-angiogenic agent avastin (bevacizumab) has been shown to confer a survival benefit in a subset of patients with previously untreated advanced NSCLC (see prior post), we have been struggling with questions of whether the restricted eligibility requirements in the pivotal initial avastin trial were necessary.  Specifically, the trial, called ECOG 4599 (abstract here) excluded patients with squamous NSCLC, known brain metastases, on full dose anticoagulation/blood thinners (not low, prophylactic doses that are occasionally used to try to prevent patients from developing blood clots), with a history of clots or bleeding problems, or with a history of coughing up blood.   While the trial was positive, these exclusion requirements have left only a minority of  real world patients in the real world eligible for avastin — most experts estimating perhaps 30-50% of advanced NSCLC patients.  Since then, the question has remained whether these exclusions are really necessary or are actually overly conservative.  For example, avastin had already been approved for patients with advanced colon cancer, in whom there is no restriction on blood thinners or presumed need to check for brain metastases in that population.  These restrictive factors have been evaluated over the last few years to try to establish whether it may be feasible to treat patients with these potentially “soft” exclusion factors with avastin.

   Patients enrolling on trials to receive avastin have historically been excluded if they had a history of brain metastases, even treated with radiation or surgery, based on a single case in a phase I trial early in avastin’s development, in which a patient with liver cancer had an unsuspected brain metastasis and developed a fatal bleeding event in the brain (abstract here).  Since then, avastin has been studied with chemo in some small trials of patients with primary brain tumors (cancers that originate in the brain, as opposed to the more commen reason for tumors in the brain, which is from spread to the brain from another source, most commonly lung cancer).  In these trials, a few dozen patients with brain cancers have received avastin, and there has been a single reported bleed in the central nervous system (CNS, basically just another way of saying “brain”) thus far (abstracts here and here).

   Since avastin was approved, there has been a change in practice for patients with advanced NSCLC.  Before avastin was approved, many oncologists did not routinely perform head MRI scans looking for brain metastases if a patient was already known to have advanced NSCLC and did not have any neurologic symptoms.  The idea was that there was little reason to look for brain metastases if some patients would never have symptoms from them, and if it didn’t need to change management.  In fact, there is some evidence that patients can have shrinkage of brain metastases from chemotherapy that is in the same range as that seen outside of the brain (post here), leaving even less incentive to jump in to treat something that could be treated along with the cancer in the chest and elsewhere.  But with avastin approved only for lung cancer patients with no evidence of brain metastases, we now go looking for brain metastases routinely in patients who are otherwise appropriate candidates for avastin.  And now that we do head MRIs looking for them, we find them more commonly than we used to suspect; I and other lung cancer experts have estimated that somewhere in the range of 10-20% of patients will now be found to have brain metastases when you look hard for them.  So there are many patients who are technically ineligible for avastin based on prior brain metastases.  On the other hand, I’ve seen many patients in second opinions who have received avastin despite their having treated brain mets; some very good oncologists just provide a careful discussion of risk and benefit balance with avastin and treat patients with brain metastases despite the potentially increased risk of bleeding, especially since we really don’t know whether we’re just being paranoid.  In fact, though, there were three patients on the avastin arm of the ECOG 4599 trial who developed bleeding in the brain, at least one of whom with new development of brain metastases that hadn’t been seen on initial presentation (Sandler, personal communication). (more…)

  The GRACE site is open and active, with all of the post content moved over, and the forum section still rather new but open for business.  I mention this because I think many OncTalk members still haven’t checked in there, but within the next few days we’re going to freeze the OncTalk forums and have all Q&A activity moving forward take place at the GRACE Discussion Forum. 

   So this would be a very good time for those with any intention of participating to try to log in see if things seem to be working OK.  From now on, your OncTalk and GRACE passwords and profiles won’t be synchronized, so if you make a new password for GRACE, this won’t work on OncTalk. 

   If you have problems, please add to the OncTalk or GRACE forums by leaving a comment in the folders soliciting for problems.  Please specify if:

1) You can’t log in

2) You tried to get the system to e-mail you a new password, but it failed. 

3) There are typos, formatting errors, etc. (I already know the text size buttons don’t work outside of the home page, and we’ll switch the them so (-) is on the left, which makes more sense to me, at least). 

4) Other significant problems

  The GRACE site also includes a very robust profle function for people to provide bios, avatar pictures, etc, so I’ll encourage you to tailor it beyond the blank text fields t add some personality, treatment background, etc.,  Also, please note that all members will initially appear as a “newbie” with no prior posts, but as people participate at GRACE I’ll correct the number of posts to reflect prior acvitity on OncTalk. 

   I’ll be checking and responding over at GRACE every day, and soon that will be the only place, so jump in and help modify it now, while the developers are still tweaking it every day or so.

   I’ve previously described the concept of the “precocious metastasis”, the situation in which a patient presents with early stage NSCLC, except for a single metastasis, most typically in the brain or adrenal gland (see prior post).  Our conventional teaching is that a patient with any metastatic disease almost certainly has additional micrometastatic disease, cancer cells floating in the bloodstream, that will inevitably lead to development of new areas of visible metastatic disease in the future (so having a small amount of metastatic disease would be like being “a little pregnant”).  But as with so much of medicine, there are few absolutes, and about 25% of patients with solitary lesions that are surgically removed (or, presumably, alternatively, radiated with an approach like sterotectic radiosurgery, but this hasn’t really been proven) can have long-term survival.  And a recent publication in the Journal of Clinical Oncology by several investigators in the lung cancer group at Moffitt Cancer Center in Tampa, FL (abstract here) provides a much needed characterization of outcomes for patients with solitary adrenal metastases who have undergone an adrenalectomy (removing one of the two adrenal glands, above the kidneys).
 
   The study was a retrospective review of published reports, with at least four patients per publication, who had undergone adrenalectomy along with treatment of their early stage NSCLC.  Importantly, the study divided patients into those who had synchronous metastases, meaning that the adrenal met was present when they first found and treated the main tumor in the chest, and metachronous lesions, which are mets that were not present initially but became evident an interval of time after a patient’s initial presentation and treatment (actually, a cutoff of six months is the usual definition of synchronous vs. metachronous). 
 
   Oncologists and surgeons have often perceived that patients with synchronous cancers are less likely to do well than those who return with a single metastasis a year or two after their treatment.  The metachronous lesion that occurs 18 months later, for instance, has already demonstrated that new lesions aren’t going to be popping up rapidly.  With a synchronous metastasis, it’s possible that this is just a snapshot in time, and the cancer is just early on its way to spreading to many areas in the body.  (more…)