|
|
|
Tumor Size as a Critical Factor in Weighing Value of Adjuvant Chemo
While there are good reasons to not pursue chemo after surgery for stage I NSCLC, there are several factors that argue at least for strong consideration of adjuvant chemotherapy for higher risk patients. Because stage IB generally has a less favorable prognosis than stage IA, it’s not suprising that the debate about which patients should or should not be receiving post-op chemo has centered more on the stage IB population, which have much more commonly been included in trials testing the value of adjuvant chemotherapy. Now we’ll focus on why tumor size has emerged as probably the most important factor in borderline cases where we might consider adjuvant chemotherapy but aren’t definitely convinced.
In my last post I enumerated reasons to not pursue adjuvant chemo for stage I patients, in whom the separation between T1 cancers and T2 cancers is usually the size, with a cutoff of greater or less than 3 cm (involvement if the pleural lining on the outer edge of the lung can also make a smaller tumor a T2 lesion). In that post, I described several positive adjuvant chemotherapy trials that did include stage IB patients, including the IALT trial (abstract here), Canadian BR.10 trial (abstract here), and the ANITA trial (abstract here), but in all of these cases, the stage I patients showed little or no benefit while the benefits were much greater for stage II and IIIA patients. And then there is the very important CALGB 9633 trial (preliminary 2004 abstract here, revised 2006 abstract here) that randomized over 300 patients, all with resected stage IB NSCLC, to 4 cycles of carbo/taxol or observation alone. As described in detail in my prior post, the preliminary results of the trial were positive overall, with a 12% improvement in overall survival at four years in recipients of carbo/taxol, but the curves came together and were not significantly different for overall survival (but were better for progresison-free survival) for those receiving adjuvant chemotherapy. But at the time that the revised negative results for the overall study were presented, Dr. Strauss presented an analysis of his trial outcomes that showed that the stage IB patients who had cancers of 4 cm or larger had a significant benefit from chemotherapy, while there was no benefit from the patients with tumors that were less than 4 cm:
(Click to enlarge images)
New Trial Starting, Studying Avastin with Adjuvant Chemo
At long last, and after years of planning, a new large phase III randomized clinical trial is getting underway to determine whether adding avastin to chemotherapy as post-operative (adjuvant) treatment for early stage NSCLC provides added benefit compared to chemotherapy alone. This trial, led by the Eastern Cooperative Oncology Group (ECOG) and with the principal investigator Heather Wakelee of Stanford, is designated E1505 and will randomize 1500 patients with stage IB (tumors of 4 cm or larger only) or stage II or IIIA NSCLC to receive four cycles of any one of three chemo regimens alone or with avastin, and the avastin arm will also receive ongoing avastin for up to a year:
(Click to enlarge)
Avastin is of great interest in this setting because adding avastin to chemo improved survival for eligible patients with advanced NSCLC by a couple of months (post here), and perhaps a better result in post-op treatment for early stage, surgical disease would translate to a significant increase in the actual cure rate for NSCLC. Continue reading
The Great Debate: Should Surgery be the “Standard of Care” for Stage IIIA NSCLC with Mediastinal Nodes?
It’s over, and I won (did you doubt me?). As I mentioned in a recent prior post, today I spoke at the Eighth International Lung Cancer Congress, where I was assigned the topic of speaking in favor of chemo/radiation as the more appropriate standard of care, with the opposing view, that surgery is the standard, taken by the esteemed Dr. Stephen Swisher, thoracic surgeon (and actually Chair of the Department) at the MD Anderson Cancer Center in Houston.
Now in truth, we didn’t differ very much in our perspectives. One key point we agreed on completely is that the stage of IIIA N2 NSCLC is a very heterogeneous group, ranging from some patients with just microscopic involvement of a single lymph node in the mediastinum (mid-chest, between the lungs) to multiple lymph nodes at multiple areas of the mediastinum that are enlarged and even bulky (more than about 2 or definitely 3 cm). In fact, within that range, outcomes are very different, with the group who have a single area of non-enlarged lymph nodes that have cancer involvement just at the microscopic level having a much better prognosis than those with enlarged nodes or with more than one mediastinal area involved:
(Click to enlarge) Continue reading
Adjuvant Chemo in Older Patients: Feasible and Beneficial?
Chemotherapy after surgery has become increasingly well established as beneficial for many patients who have undergone surgery for early stage NSCLC, at least for stage II and IIIA resected disease (stage IB has had more mixed results and remains quite debatable). The chemo regimens that have been most clearly shown to confer improved survival are cisplatin-based and can have very challenging toxicity in anybody, especially after a major lung surgery. In fact, the rates of administering chemo as planned after surgery are generally about 65-75%, and this is in clinically trials that tend to enroll disproportionately younger, fitter, and more aggressively-minded patients than are seen in a broader “real world” experience. So the question of how feasible it is to administer post-operative chemo in older and potentially less robust patients is an important issue. Do such patients receive a benefit similar to that seen in younger patients, or does adjuvant chemo potentially represent treatment beyond the point of benefit that may do more harm than good? We don’t have much information, but one study presented last year provides some useful information that indicates that adjuvant chemotherapy appears to be at least of equal benefit in older compared to younger patients. Continue reading
What are the Right Drugs for Adjuvant (Post-Operative) Chemotherapy?
For many patients with early stage, resected NSCLC, chemotherapy after surgery may be a strong consideration to minimize the chance of the cancer returning, in which cases, it is often not possible to cure it. Several clinical trials over the past few years have shown benefits from chemo combinations, but which ones would be the leading considerations now? Continue reading
| Follow us on... |    |
||
Copyright ©2012 GRACE |
|||