HER2 Support Group Forums - View Single Post - for those with brain mets or leptomeningeal mets

Lani · 05-11-2013, 05:34 PM

a new review paper from Dana Farber's Nancy Lin rehashes what has been tried and what is new and upcoming.

On L-M mets it states:

From an investigational standpoint, given that HER2 amplification appears to be retained in patients with HER2-positive primary tumours and leptomeningeal involvement, intrathecal trastuzumab is the subject of two ongoing prospective trials in France and in the United States (www.clinicaltrials.gov; NCT01373710, NCT01325207) [86]. A number of case reports have been published in the medical literature, although on close review, in many cases, patients received multiple concurrent therapies, making isolation of the true effect of intrathecal trastuzumab a challenge [87–89]. At present, off-label use of intrathecal trastuzumab is not recommended, given that the commercial drug supply is not formulated for intrathecal use [90]. Newer anti-HER2 agents, such as pertuzumab or TDM1, which have demonstrated activity against extracranial metastases, could also be of interest in patients with leptomeningeal disease when given intrathecally. However, these would need to be studied carefully for both safety and efficacy and, as of now, would not be recommended for off-label use in this setting [91–93].

Since she has just reviewed how little effect one can expect with other treatments of leptomeningeal mets these pious "is not recommended" and "would not be recommended"
may not go a long way with patients/their caregivers and oncologist really just trying to help them. Wouldn't it be better just not to publish those in a review than put in black and white words which preclude any but the most brave oncologists from offering the drugs,especially as those patients often don't feel well enough to travel for the trials and the number of patients with LM mets at any one or two or three institutions is such that trials may take decades?

Just bringing up for discussion what is the role for informed consent and off-label use outside clinical trials in conditions that are relatively rare and imminently lethal with no other good treatment options.

I usually do not get "political" but sometimes I wish these words would not get used. It keeps insurance for paying for things they might otherwise be obliged to under state or federal law (off label use), frightens oncologist who might otherwise just be willing to try treatments on the basis of previously reported good results, hinders progress in finding solutions for these hard to treat mets and erases hope from those who need it as another door is shut in their face. I can of course, see the other point of view--first do not harm, not wanting to get sued for practicing less than the standard of care, etc--

Can any of you devise a better way to solve this dilemma?

05-11-2013, 05:34 PM	#1
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	for those with brain mets or leptomeningeal mets a new review paper from Dana Farber's Nancy Lin rehashes what has been tried and what is new and upcoming. On L-M mets it states: From an investigational standpoint, given that HER2 amplification appears to be retained in patients with HER2-positive primary tumours and leptomeningeal involvement, intrathecal trastuzumab is the subject of two ongoing prospective trials in France and in the United States (www.clinicaltrials.gov; NCT01373710, NCT01325207) [86]. A number of case reports have been published in the medical literature, although on close review, in many cases, patients received multiple concurrent therapies, making isolation of the true effect of intrathecal trastuzumab a challenge [87–89]. At present, off-label use of intrathecal trastuzumab is not recommended, given that the commercial drug supply is not formulated for intrathecal use [90]. Newer anti-HER2 agents, such as pertuzumab or TDM1, which have demonstrated activity against extracranial metastases, could also be of interest in patients with leptomeningeal disease when given intrathecally. However, these would need to be studied carefully for both safety and efficacy and, as of now, would not be recommended for off-label use in this setting [91–93]. Since she has just reviewed how little effect one can expect with other treatments of leptomeningeal mets these pious "is not recommended" and "would not be recommended" may not go a long way with patients/their caregivers and oncologist really just trying to help them. Wouldn't it be better just not to publish those in a review than put in black and white words which preclude any but the most brave oncologists from offering the drugs,especially as those patients often don't feel well enough to travel for the trials and the number of patients with LM mets at any one or two or three institutions is such that trials may take decades? Just bringing up for discussion what is the role for informed consent and off-label use outside clinical trials in conditions that are relatively rare and imminently lethal with no other good treatment options. I usually do not get "political" but sometimes I wish these words would not get used. It keeps insurance for paying for things they might otherwise be obliged to under state or federal law (off label use), frightens oncologist who might otherwise just be willing to try treatments on the basis of previously reported good results, hinders progress in finding solutions for these hard to treat mets and erases hope from those who need it as another door is shut in their face. I can of course, see the other point of view--first do not harm, not wanting to get sued for practicing less than the standard of care, etc-- Can any of you devise a better way to solve this dilemma?