Why Would NSCLC Guidelines Say THAT?
Why Would NSCLC Guidelines Say THAT?
This is Mark Kris from Memorial Sloan-Kettering, commenting today with a reaction to the publication of guideline updates by major professional organizations. This updated guideline is from the American Society of Clinical Oncology (ASCO) and it appeared in the October 1, 2011, issue of the Journal of Clinical Oncology and is titled "2011 Focused Update of the 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small Cell Lung Cancer."
This guideline update is unusual and contains many areas that require very careful reading. I am encouraging you to read this article very closely. Some very important points are made, but others could be misconstrued without very careful reading.
The first point I would like to call your attention to is the comment that first-line cytotoxic chemotherapy should be stopped at disease progression or after 4 cycles in patients whose disease is stable but not responding to treatment. It is common sense that we very carefully make that risk-benefit evaluation for patients with advanced non-small cell lung cancer with every cycle of chemotherapy. It is a constant balance of risk, benefit, appropriateness for that patient, and acceptability to that patient. You really need to do that at every cycle. It is quite important to make that tough call with every cycle because you do not want to continue with therapy that is not substantially benefiting the patient, either by your objective measures or by the patient's own measure of how that medicine is helping them.
The term "stable disease" is a very difficult one. Please remember that when using the RECIST criteria for stable disease, it goes from 19% disease growth to 29% disease shrinkage. Remember, 30% is partial remission. It is very important to make sure that you look at the nuances of the term "stable disease," and frankly, as soon as you can tell that the medicine is not benefiting the patient, either by tumor growth, poor tolerability, or the patient's feelings about what that chemotherapy is doing, how much it is adding to the quality of life, those drugs need to be stopped regardless of the numbers of cycles of therapy.
If you have determined that the medicines are well tolerated, that the patient feels that the side effect:benefit ratio is in a direction that they feel is appropriate, and you have continued shrinkage of that cancer, then you continue those drugs. All the data on the continuation of maintenance support that. Although not discussed in these guidelines, there are clear data that continuing pemetrexed, gemcitabine, bevacizumab, and cetuximab is reasonable and supported by clinical trial data (some of them for switch maintenance and all of them for continuation maintenance -- docetaxel as well for switch maintenance).
For people who are responding, it makes sense to continue the therapy. For people who are not responding, stop that drug as soon as you can.
There are also a couple of other issues to which you should pay close attention. In the discussion of bevacizumab, the guideline first states that bevacizumab can only be given with carboplatin and paclitaxel. Randomized trials show that bevacizumab can be safely given with other chemotherapy regimens, and it is the opinion of other guideline groups that you can give bevacizumab with virtually any chemotherapy regimen that is appropriate for stage IV lung cancer. It is very difficult to be prescriptive and say it can only be given with carboplatin and paclitaxel, particularly when we know that it is probably not the best therapy, particularly for the adenocarcinoma patients who will benefit from pemetrexed.
A second point about bevacizumab is that [the guidelines] continue to include outdated restrictions. The first is that you cannot give bevacizumab safely in patients who are on therapeutic anticoagulation. That is just not the standard of care right now. It has been shown very clearly in colorectal cancer and in many years of use in lung cancer patients (who by and large are not on warfarin) that the drug is safe.
Lastly, there are good data from clinical trials that it is safe to give bevacizumab in patients with brain metastases, except those with overt intracranial hemorrhage. Bevacizumab, as you know, is an approved agent for patients with primary brain tumors and there is every reason to think it can help with central nervous system disease from non-small cell lung cancer as well. Safety data have been published already and it is no longer an absolute contraindication that the presence of a brain metastasis would preclude the use of bevacizumab.
Many of you are following that literature about the use of bevacizumab in either preventing or treating radionecrosis, a very common problem, particularly with stereotactic radiotherapy.
The last comment is about the last line of the guidelines' summary table. They make the statement that "Evidence is insufficient to recommend routine use of molecular markers to select systemic treatment in patients with metastatic non-small cell lung cancer." An asterisk leads to another comment from ASCO, who issued a provisional clinical opinion on epidermal growth factor receptor (EGFR) and testing, saying that testing should be done. It is the standard of care now to perform testing for EGFR mutations and ALK rearrangements at diagnosis in all patients who have a non-small cell lung cancer that is not squamous cell. If you read these ASCO guidelines carefully and go to that provisional clinical opinion, you will see that conclusion there, too. With a cursory reading of the guidelines, it says that evidence is insufficient to support that. I think all experts in the field would agree that that is not the case. Again, with a careful reading of the ASCO guidelines, they support that as well.
This is an example of being very careful in the reading of the medical literature, looking at all the data, not just data that can be used to support specific recommendations based on randomized controlled trials. As you know, many of the things we do can't be supported in that way. I urge a very careful reading of these ASCO guidelines and that you look at the whole literature to make the best decisions for your patients.
This is Mark Kris from Memorial Sloan-Kettering, commenting today with a reaction to the publication of guideline updates by major professional organizations. This updated guideline is from the American Society of Clinical Oncology (ASCO) and it appeared in the October 1, 2011, issue of the Journal of Clinical Oncology and is titled "2011 Focused Update of the 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small Cell Lung Cancer."
This guideline update is unusual and contains many areas that require very careful reading. I am encouraging you to read this article very closely. Some very important points are made, but others could be misconstrued without very careful reading.
The first point I would like to call your attention to is the comment that first-line cytotoxic chemotherapy should be stopped at disease progression or after 4 cycles in patients whose disease is stable but not responding to treatment. It is common sense that we very carefully make that risk-benefit evaluation for patients with advanced non-small cell lung cancer with every cycle of chemotherapy. It is a constant balance of risk, benefit, appropriateness for that patient, and acceptability to that patient. You really need to do that at every cycle. It is quite important to make that tough call with every cycle because you do not want to continue with therapy that is not substantially benefiting the patient, either by your objective measures or by the patient's own measure of how that medicine is helping them.
The term "stable disease" is a very difficult one. Please remember that when using the RECIST criteria for stable disease, it goes from 19% disease growth to 29% disease shrinkage. Remember, 30% is partial remission. It is very important to make sure that you look at the nuances of the term "stable disease," and frankly, as soon as you can tell that the medicine is not benefiting the patient, either by tumor growth, poor tolerability, or the patient's feelings about what that chemotherapy is doing, how much it is adding to the quality of life, those drugs need to be stopped regardless of the numbers of cycles of therapy.
If you have determined that the medicines are well tolerated, that the patient feels that the side effect:benefit ratio is in a direction that they feel is appropriate, and you have continued shrinkage of that cancer, then you continue those drugs. All the data on the continuation of maintenance support that. Although not discussed in these guidelines, there are clear data that continuing pemetrexed, gemcitabine, bevacizumab, and cetuximab is reasonable and supported by clinical trial data (some of them for switch maintenance and all of them for continuation maintenance -- docetaxel as well for switch maintenance).
For people who are responding, it makes sense to continue the therapy. For people who are not responding, stop that drug as soon as you can.
There are also a couple of other issues to which you should pay close attention. In the discussion of bevacizumab, the guideline first states that bevacizumab can only be given with carboplatin and paclitaxel. Randomized trials show that bevacizumab can be safely given with other chemotherapy regimens, and it is the opinion of other guideline groups that you can give bevacizumab with virtually any chemotherapy regimen that is appropriate for stage IV lung cancer. It is very difficult to be prescriptive and say it can only be given with carboplatin and paclitaxel, particularly when we know that it is probably not the best therapy, particularly for the adenocarcinoma patients who will benefit from pemetrexed.
A second point about bevacizumab is that [the guidelines] continue to include outdated restrictions. The first is that you cannot give bevacizumab safely in patients who are on therapeutic anticoagulation. That is just not the standard of care right now. It has been shown very clearly in colorectal cancer and in many years of use in lung cancer patients (who by and large are not on warfarin) that the drug is safe.
Lastly, there are good data from clinical trials that it is safe to give bevacizumab in patients with brain metastases, except those with overt intracranial hemorrhage. Bevacizumab, as you know, is an approved agent for patients with primary brain tumors and there is every reason to think it can help with central nervous system disease from non-small cell lung cancer as well. Safety data have been published already and it is no longer an absolute contraindication that the presence of a brain metastasis would preclude the use of bevacizumab.
Many of you are following that literature about the use of bevacizumab in either preventing or treating radionecrosis, a very common problem, particularly with stereotactic radiotherapy.
The last comment is about the last line of the guidelines' summary table. They make the statement that "Evidence is insufficient to recommend routine use of molecular markers to select systemic treatment in patients with metastatic non-small cell lung cancer." An asterisk leads to another comment from ASCO, who issued a provisional clinical opinion on epidermal growth factor receptor (EGFR) and testing, saying that testing should be done. It is the standard of care now to perform testing for EGFR mutations and ALK rearrangements at diagnosis in all patients who have a non-small cell lung cancer that is not squamous cell. If you read these ASCO guidelines carefully and go to that provisional clinical opinion, you will see that conclusion there, too. With a cursory reading of the guidelines, it says that evidence is insufficient to support that. I think all experts in the field would agree that that is not the case. Again, with a careful reading of the ASCO guidelines, they support that as well.
This is an example of being very careful in the reading of the medical literature, looking at all the data, not just data that can be used to support specific recommendations based on randomized controlled trials. As you know, many of the things we do can't be supported in that way. I urge a very careful reading of these ASCO guidelines and that you look at the whole literature to make the best decisions for your patients.
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