› Forums › General Melanoma Community › Partial Response to IPI?
- This topic has 18 replies, 4 voices, and was last updated 10 years, 3 months ago by
Janet Lee.
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- January 20, 2014 at 2:39 am
Hi. My husband, Don, was diagnosed Stage IV last year at this time. Since then he has had radiation to his pelvis for excruciatingly painful but inoperable mets, cyberknife for one brain met (Feb), craniotomy to remove that met (Mar), rehabilitation to recover from effects of brain met, cyberknife again for 3 additional brain mets (May), SRS for yet 2 more brain mets (Aug), surgery to remove mass in inguinal canal ((Oct), and is now facing radiation for at least two fast-growing inoperable mets in pelvic area. He is BRAF positive, but for V600R, not E. We had to fight the insurance comapny for Zelboraf, which helped him for about 4-6 weeks (Apr). He had 4 doses of IPI (May-July), and his doctor says he is responding to the IPI.His brain has been stable since the August SRS, and adrenal met and lung nodules are shrinking or holding steady.
But, if he is responding to IPI, is it possible that this is a "partial" response? The oncologist has been saying he is definitely responding, and yet BAM! the mass in his inguinal grew rapidly, causing much pain, and was surgically removed. Two months later, scans look good everywhere else except the pelvic area again, this time a lymph node which has doubled in size. Now, each day he is much worse, is in terrible pain, and he will start radiation next week.
My question: is there such a thing as a partial response to IPI? Should we be looking at another treatment? I'm concerned about radiating the pelvic area a second time, but what if more mets continue to develop in this area? This seems like an awful lot of activity to me in this area which is obviously not responding to the Ipi.
Should we be looking to get into an Anti-PD1 trial? Is the latest MEK-and something combo (forgot the name, sorry!) only for V600E BRAF patients?
Thanks for your thoughts and opinions!
Janet Lee
- Replies
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- January 20, 2014 at 9:17 am
Janet, I share Your concern about a lot of radiation to the abdomen. I avoided abdominal radiation myself because of how extensive they talked about doing it.
Radiation seldom eliminates Melanoma tumors outside the brain. It is often used to reduce the tumor load in the body, while not removing the tumor. If all the other tumors are responding to the Ipi, I suggest talking to your Oncologist about the possibility of direct injections into the one growing tumor. Possibly Rose Bengal, or IL-2. PD-1 might work or might not (about a 50% chance.) Another possibility would be to implant some radiactive pellets into the tumor. Dr Webber at Moffet would be a good source of info about the possibility of PD-1. and other treatments. ([email protected]) It is rather unusual for one tumor to continue growing widly while all the other body tumors are responding to Ipi. -
- January 20, 2014 at 9:17 am
Janet, I share Your concern about a lot of radiation to the abdomen. I avoided abdominal radiation myself because of how extensive they talked about doing it.
Radiation seldom eliminates Melanoma tumors outside the brain. It is often used to reduce the tumor load in the body, while not removing the tumor. If all the other tumors are responding to the Ipi, I suggest talking to your Oncologist about the possibility of direct injections into the one growing tumor. Possibly Rose Bengal, or IL-2. PD-1 might work or might not (about a 50% chance.) Another possibility would be to implant some radiactive pellets into the tumor. Dr Webber at Moffet would be a good source of info about the possibility of PD-1. and other treatments. ([email protected]) It is rather unusual for one tumor to continue growing widly while all the other body tumors are responding to Ipi. -
- January 20, 2014 at 9:17 am
Janet, I share Your concern about a lot of radiation to the abdomen. I avoided abdominal radiation myself because of how extensive they talked about doing it.
Radiation seldom eliminates Melanoma tumors outside the brain. It is often used to reduce the tumor load in the body, while not removing the tumor. If all the other tumors are responding to the Ipi, I suggest talking to your Oncologist about the possibility of direct injections into the one growing tumor. Possibly Rose Bengal, or IL-2. PD-1 might work or might not (about a 50% chance.) Another possibility would be to implant some radiactive pellets into the tumor. Dr Webber at Moffet would be a good source of info about the possibility of PD-1. and other treatments. ([email protected]) It is rather unusual for one tumor to continue growing widly while all the other body tumors are responding to Ipi. -
- January 20, 2014 at 9:17 am
Janet, I share Your concern about a lot of radiation to the abdomen. I avoided abdominal radiation myself because of how extensive they talked about doing it.
Radiation seldom eliminates Melanoma tumors outside the brain. It is often used to reduce the tumor load in the body, while not removing the tumor. If all the other tumors are responding to the Ipi, I suggest talking to your Oncologist about the possibility of direct injections into the one growing tumor. Possibly Rose Bengal, or IL-2. PD-1 might work or might not (about a 50% chance.) Another possibility would be to implant some radiactive pellets into the tumor. Dr Webber at Moffet would be a good source of info about the possibility of PD-1. and other treatments. ([email protected]) It is rather unusual for one tumor to continue growing widly while all the other body tumors are responding to Ipi.-
- January 20, 2014 at 9:33 am
COMBINATION REGIMENS
Combined anti-CTLA-4 and anti-PD-1 immunotherapy — The combined administration of anti-CTLA-4 immunotherapy with ipilimumab plus anti-PD-1 immunotherapy with nivolumab appears to have a higher level of anti-melanoma activity that either agent alone and has a manageable toxicity profile [53].
The combination was assessed in a phase I trial in which both drugs were given in successive dose escalation cohorts. In a concurrent therapy cohort, 53 patients with advanced melanoma were treated with both drugs once every three weeks for four doses. Nivolumab was then continued every three weeks through week 24. Subsequently, therapy with both drugs was continued once every 12 weeks for a maximum of eight additional doses. In a separate sequential cohort, nivolumab was given on the same schedule to 33 patients who had received prior ipilimumab.
In the concurrent treatment cohort, 21 of 52 evaluable patients (40 percent) had an objective response, and 16 of the 21 had an 80 percent or greater reduction in the tumor burden. Responses were ongoing in 19 of 21 patients at the time of data analysis, with duration of response up to 72 weeks. Evidence of clinical activity (stable disease or greater for at least 24 weeks) was observed in 65 percent of patients. In the sequenced therapy group (ie, nivolumab given after prior ipilimumab treatment), 6 of 30 patients had an objective response.
Among the patients treated with concurrent nivolumab plus ipilimumab, treatment-related adverse events were observed in 93 percent of cases. The most common events of any degree of severity were rash, pruritus, fatigue, and diarrhea (55, 47, 38, and 34 percent, respectively). Severe treatment related adverse events were reported in 49 percent of cases, including liver, gastrointestinal, and kidney toxicity (15, 9, and 6 percent of cases, respectively). Treatment was discontinued because of adverse events in 11 cases (21 percent).
Additional clinical experience and longer follow-up will be required to determine the optimal dose and schedule for concurrent immune checkpoint therapy as well as its role in the management of patients with advanced melanoma. A phase III trial is studying the combination of nivolumab plus ipilimumab compared with each of these other checkpoint inhibitors as a single agent (NCT01844505).
Ipilimumab plus GM-CSF — The addition of granulocyte-macrophage (GM) colony-stimulating factor (CSF) to ipilimumab was studied in a phase II trial conducted by Eastern Cooperative Oncology Group (ECOG).
In this trial, 245 patients with advanced melanoma were randomly assigned to ipilimumab plus GM-CSF or ipilimumab alone [54]. Ipilimumab was given at a dose of 10 mg/kg every three weeks for four cycles, followed by maintenance every 12 weeks. GM-CSF (250 micrograms/day subcutaneously) was given on days 1 to 14 of each 21 day cycle.
Results of this trial were presented at the 2013 American Society of Clinical Oncology (ASCO) meeting. At a median follow-up of 13 months, there was no difference in the objective response rate with or without GM-CSF (15.5 and 14.8 percent, respectively). There also was no significant difference in the progression-free survival (34.0 versus 29.6 percent at 6 months, hazard ratio [HR] 0.92, 95% CI 0.69-1.23). However, overall survival was significantly improved by the addition of GM-CSF (median 17.5 versus 12.7 months, one-year survival rates 69 versus 53 percent, HR 0.64, p = 0.014).
The addition of GM-CSF resulted in a significant reduction in the incidence of high grade adverse events, particularly related to pulmonary and gastrointestinal toxicity. The extent to which this decrease in toxicity contributed to the improved overall survival is unclear.
It is important to note that this trial used a higher dose of ipilimumab than is currently approved and that maintenance therapy was also included as a component of the protocol. The clinical implications of these results will require further study and confirmation.
OTHER IMMUNE REGULATORY CHECKPOINTS — Monoclonal antibodies targeted against a number of other regulatory checkpoints are being evaluated in patients with advanced melanoma based upon our current understanding of the development of cellular immunity.
4-1BB — 4-1BB (CD137) is a member of the tumor necrosis factor (TNF) family and acts as a costimulatory molecule that causes T cell proliferation. A humanized MAb, BMS-663513, targe
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- January 20, 2014 at 9:33 am
COMBINATION REGIMENS
Combined anti-CTLA-4 and anti-PD-1 immunotherapy — The combined administration of anti-CTLA-4 immunotherapy with ipilimumab plus anti-PD-1 immunotherapy with nivolumab appears to have a higher level of anti-melanoma activity that either agent alone and has a manageable toxicity profile [53].
The combination was assessed in a phase I trial in which both drugs were given in successive dose escalation cohorts. In a concurrent therapy cohort, 53 patients with advanced melanoma were treated with both drugs once every three weeks for four doses. Nivolumab was then continued every three weeks through week 24. Subsequently, therapy with both drugs was continued once every 12 weeks for a maximum of eight additional doses. In a separate sequential cohort, nivolumab was given on the same schedule to 33 patients who had received prior ipilimumab.
In the concurrent treatment cohort, 21 of 52 evaluable patients (40 percent) had an objective response, and 16 of the 21 had an 80 percent or greater reduction in the tumor burden. Responses were ongoing in 19 of 21 patients at the time of data analysis, with duration of response up to 72 weeks. Evidence of clinical activity (stable disease or greater for at least 24 weeks) was observed in 65 percent of patients. In the sequenced therapy group (ie, nivolumab given after prior ipilimumab treatment), 6 of 30 patients had an objective response.
Among the patients treated with concurrent nivolumab plus ipilimumab, treatment-related adverse events were observed in 93 percent of cases. The most common events of any degree of severity were rash, pruritus, fatigue, and diarrhea (55, 47, 38, and 34 percent, respectively). Severe treatment related adverse events were reported in 49 percent of cases, including liver, gastrointestinal, and kidney toxicity (15, 9, and 6 percent of cases, respectively). Treatment was discontinued because of adverse events in 11 cases (21 percent).
Additional clinical experience and longer follow-up will be required to determine the optimal dose and schedule for concurrent immune checkpoint therapy as well as its role in the management of patients with advanced melanoma. A phase III trial is studying the combination of nivolumab plus ipilimumab compared with each of these other checkpoint inhibitors as a single agent (NCT01844505).
Ipilimumab plus GM-CSF — The addition of granulocyte-macrophage (GM) colony-stimulating factor (CSF) to ipilimumab was studied in a phase II trial conducted by Eastern Cooperative Oncology Group (ECOG).
In this trial, 245 patients with advanced melanoma were randomly assigned to ipilimumab plus GM-CSF or ipilimumab alone [54]. Ipilimumab was given at a dose of 10 mg/kg every three weeks for four cycles, followed by maintenance every 12 weeks. GM-CSF (250 micrograms/day subcutaneously) was given on days 1 to 14 of each 21 day cycle.
Results of this trial were presented at the 2013 American Society of Clinical Oncology (ASCO) meeting. At a median follow-up of 13 months, there was no difference in the objective response rate with or without GM-CSF (15.5 and 14.8 percent, respectively). There also was no significant difference in the progression-free survival (34.0 versus 29.6 percent at 6 months, hazard ratio [HR] 0.92, 95% CI 0.69-1.23). However, overall survival was significantly improved by the addition of GM-CSF (median 17.5 versus 12.7 months, one-year survival rates 69 versus 53 percent, HR 0.64, p = 0.014).
The addition of GM-CSF resulted in a significant reduction in the incidence of high grade adverse events, particularly related to pulmonary and gastrointestinal toxicity. The extent to which this decrease in toxicity contributed to the improved overall survival is unclear.
It is important to note that this trial used a higher dose of ipilimumab than is currently approved and that maintenance therapy was also included as a component of the protocol. The clinical implications of these results will require further study and confirmation.
OTHER IMMUNE REGULATORY CHECKPOINTS — Monoclonal antibodies targeted against a number of other regulatory checkpoints are being evaluated in patients with advanced melanoma based upon our current understanding of the development of cellular immunity.
4-1BB — 4-1BB (CD137) is a member of the tumor necrosis factor (TNF) family and acts as a costimulatory molecule that causes T cell proliferation. A humanized MAb, BMS-663513, targe
-
- January 20, 2014 at 9:33 am
COMBINATION REGIMENS
Combined anti-CTLA-4 and anti-PD-1 immunotherapy — The combined administration of anti-CTLA-4 immunotherapy with ipilimumab plus anti-PD-1 immunotherapy with nivolumab appears to have a higher level of anti-melanoma activity that either agent alone and has a manageable toxicity profile [53].
The combination was assessed in a phase I trial in which both drugs were given in successive dose escalation cohorts. In a concurrent therapy cohort, 53 patients with advanced melanoma were treated with both drugs once every three weeks for four doses. Nivolumab was then continued every three weeks through week 24. Subsequently, therapy with both drugs was continued once every 12 weeks for a maximum of eight additional doses. In a separate sequential cohort, nivolumab was given on the same schedule to 33 patients who had received prior ipilimumab.
In the concurrent treatment cohort, 21 of 52 evaluable patients (40 percent) had an objective response, and 16 of the 21 had an 80 percent or greater reduction in the tumor burden. Responses were ongoing in 19 of 21 patients at the time of data analysis, with duration of response up to 72 weeks. Evidence of clinical activity (stable disease or greater for at least 24 weeks) was observed in 65 percent of patients. In the sequenced therapy group (ie, nivolumab given after prior ipilimumab treatment), 6 of 30 patients had an objective response.
Among the patients treated with concurrent nivolumab plus ipilimumab, treatment-related adverse events were observed in 93 percent of cases. The most common events of any degree of severity were rash, pruritus, fatigue, and diarrhea (55, 47, 38, and 34 percent, respectively). Severe treatment related adverse events were reported in 49 percent of cases, including liver, gastrointestinal, and kidney toxicity (15, 9, and 6 percent of cases, respectively). Treatment was discontinued because of adverse events in 11 cases (21 percent).
Additional clinical experience and longer follow-up will be required to determine the optimal dose and schedule for concurrent immune checkpoint therapy as well as its role in the management of patients with advanced melanoma. A phase III trial is studying the combination of nivolumab plus ipilimumab compared with each of these other checkpoint inhibitors as a single agent (NCT01844505).
Ipilimumab plus GM-CSF — The addition of granulocyte-macrophage (GM) colony-stimulating factor (CSF) to ipilimumab was studied in a phase II trial conducted by Eastern Cooperative Oncology Group (ECOG).
In this trial, 245 patients with advanced melanoma were randomly assigned to ipilimumab plus GM-CSF or ipilimumab alone [54]. Ipilimumab was given at a dose of 10 mg/kg every three weeks for four cycles, followed by maintenance every 12 weeks. GM-CSF (250 micrograms/day subcutaneously) was given on days 1 to 14 of each 21 day cycle.
Results of this trial were presented at the 2013 American Society of Clinical Oncology (ASCO) meeting. At a median follow-up of 13 months, there was no difference in the objective response rate with or without GM-CSF (15.5 and 14.8 percent, respectively). There also was no significant difference in the progression-free survival (34.0 versus 29.6 percent at 6 months, hazard ratio [HR] 0.92, 95% CI 0.69-1.23). However, overall survival was significantly improved by the addition of GM-CSF (median 17.5 versus 12.7 months, one-year survival rates 69 versus 53 percent, HR 0.64, p = 0.014).
The addition of GM-CSF resulted in a significant reduction in the incidence of high grade adverse events, particularly related to pulmonary and gastrointestinal toxicity. The extent to which this decrease in toxicity contributed to the improved overall survival is unclear.
It is important to note that this trial used a higher dose of ipilimumab than is currently approved and that maintenance therapy was also included as a component of the protocol. The clinical implications of these results will require further study and confirmation.
OTHER IMMUNE REGULATORY CHECKPOINTS — Monoclonal antibodies targeted against a number of other regulatory checkpoints are being evaluated in patients with advanced melanoma based upon our current understanding of the development of cellular immunity.
4-1BB — 4-1BB (CD137) is a member of the tumor necrosis factor (TNF) family and acts as a costimulatory molecule that causes T cell proliferation. A humanized MAb, BMS-663513, targe
-
- January 20, 2014 at 9:17 am
Janet, I share Your concern about a lot of radiation to the abdomen. I avoided abdominal radiation myself because of how extensive they talked about doing it.
Radiation seldom eliminates Melanoma tumors outside the brain. It is often used to reduce the tumor load in the body, while not removing the tumor. If all the other tumors are responding to the Ipi, I suggest talking to your Oncologist about the possibility of direct injections into the one growing tumor. Possibly Rose Bengal, or IL-2. PD-1 might work or might not (about a 50% chance.) Another possibility would be to implant some radiactive pellets into the tumor. Dr Webber at Moffet would be a good source of info about the possibility of PD-1. and other treatments. ([email protected]) It is rather unusual for one tumor to continue growing widly while all the other body tumors are responding to Ipi. -
- January 20, 2014 at 9:17 am
Janet, I share Your concern about a lot of radiation to the abdomen. I avoided abdominal radiation myself because of how extensive they talked about doing it.
Radiation seldom eliminates Melanoma tumors outside the brain. It is often used to reduce the tumor load in the body, while not removing the tumor. If all the other tumors are responding to the Ipi, I suggest talking to your Oncologist about the possibility of direct injections into the one growing tumor. Possibly Rose Bengal, or IL-2. PD-1 might work or might not (about a 50% chance.) Another possibility would be to implant some radiactive pellets into the tumor. Dr Webber at Moffet would be a good source of info about the possibility of PD-1. and other treatments. ([email protected]) It is rather unusual for one tumor to continue growing widly while all the other body tumors are responding to Ipi. -
- January 20, 2014 at 12:29 pm
I am so sorry to hear that Don is having to go through all this. As you say, it is especially frustrating and confusing that the ipi seems to be working everywhere except in the abdomen. What the heck??!!
I am afraid that I do not have any specific recommendations for you. One thing you might discuss with your doctors– at least for a temporary "quick fix"– is the dabrafenib (Tafinlar) + MEK (Mekinist) combo. Unfortunately, the FDA approved the combo only for V600E or K mutations and Don is V600R.
I did find one article out of Australia that claims that Tafinlar works better on V600R than it does on the other V600 mutations (see http://www.ncbi.nlm.nih.gov/pubmed/23237741 ). I did not purchase the complete article so I don't know the details of the study. If you want to know more or see if there are any new data about V600R, you could email the senior author at [email protected]
Good luck!
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- January 20, 2014 at 12:29 pm
I am so sorry to hear that Don is having to go through all this. As you say, it is especially frustrating and confusing that the ipi seems to be working everywhere except in the abdomen. What the heck??!!
I am afraid that I do not have any specific recommendations for you. One thing you might discuss with your doctors– at least for a temporary "quick fix"– is the dabrafenib (Tafinlar) + MEK (Mekinist) combo. Unfortunately, the FDA approved the combo only for V600E or K mutations and Don is V600R.
I did find one article out of Australia that claims that Tafinlar works better on V600R than it does on the other V600 mutations (see http://www.ncbi.nlm.nih.gov/pubmed/23237741 ). I did not purchase the complete article so I don't know the details of the study. If you want to know more or see if there are any new data about V600R, you could email the senior author at [email protected]
Good luck!
-
- January 20, 2014 at 12:29 pm
I am so sorry to hear that Don is having to go through all this. As you say, it is especially frustrating and confusing that the ipi seems to be working everywhere except in the abdomen. What the heck??!!
I am afraid that I do not have any specific recommendations for you. One thing you might discuss with your doctors– at least for a temporary "quick fix"– is the dabrafenib (Tafinlar) + MEK (Mekinist) combo. Unfortunately, the FDA approved the combo only for V600E or K mutations and Don is V600R.
I did find one article out of Australia that claims that Tafinlar works better on V600R than it does on the other V600 mutations (see http://www.ncbi.nlm.nih.gov/pubmed/23237741 ). I did not purchase the complete article so I don't know the details of the study. If you want to know more or see if there are any new data about V600R, you could email the senior author at [email protected]
Good luck!
-
- January 20, 2014 at 2:09 pm
Janet,
rumor has it that Dr Weber (Moffitt) has a few slots in a new PD1 trial. People have certainly seen great success when it works. I had at best, a partial response. I am now on dabrafenib/Mekinist (and v600d), not sure if it's working, should find out soon, but this is certainly an option. Unfortunately partial responses are not uncommon with any of these drugs.
Blessings,
Amy
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- January 20, 2014 at 2:09 pm
Janet,
rumor has it that Dr Weber (Moffitt) has a few slots in a new PD1 trial. People have certainly seen great success when it works. I had at best, a partial response. I am now on dabrafenib/Mekinist (and v600d), not sure if it's working, should find out soon, but this is certainly an option. Unfortunately partial responses are not uncommon with any of these drugs.
Blessings,
Amy
-
- January 20, 2014 at 2:09 pm
Janet,
rumor has it that Dr Weber (Moffitt) has a few slots in a new PD1 trial. People have certainly seen great success when it works. I had at best, a partial response. I am now on dabrafenib/Mekinist (and v600d), not sure if it's working, should find out soon, but this is certainly an option. Unfortunately partial responses are not uncommon with any of these drugs.
Blessings,
Amy
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- January 22, 2014 at 12:50 am
Thank you all for your comments and suggestions. Our oncologist said, "Radiation first. No PD1 trials open now." Jerry, you are always such a fount of knowledge! Hopefully radiation will start tomorrow (I don't care how much snow is out there!)
Janet
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- January 22, 2014 at 12:50 am
Thank you all for your comments and suggestions. Our oncologist said, "Radiation first. No PD1 trials open now." Jerry, you are always such a fount of knowledge! Hopefully radiation will start tomorrow (I don't care how much snow is out there!)
Janet
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- January 22, 2014 at 12:50 am
Thank you all for your comments and suggestions. Our oncologist said, "Radiation first. No PD1 trials open now." Jerry, you are always such a fount of knowledge! Hopefully radiation will start tomorrow (I don't care how much snow is out there!)
Janet
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