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Tina D.
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- March 25, 2013 at 5:36 pm
Efficacy and Safety of Retreatment With Ipilimumab in Patients With Pretreated Advanced Melanoma Who Progressed After Initially Achieving Disease Control
Clin Cancer Res. 2013 Feb 26;[Epub Ahead of Print] , C Robert, D Schadendorf, M Messina, et al
Efficacy and Safety of Retreatment With Ipilimumab in Patients With Pretreated Advanced Melanoma Who Progressed After Initially Achieving Disease Control
Clin Cancer Res. 2013 Feb 26;[Epub Ahead of Print] , C Robert, D Schadendorf, M Messina, et al
TAKE-HOME MESSAGE
The investigators in this retrospective study of patients with late-stage melanoma who responded to initial treatment and were retreated with ipilumumab after progression, concluded that durable response/stable disease was achieved without added toxicity.
SUMMARY
OncologySTAT Editorial Team
It is well known that the immune system plays a dual role in cancer. It can suppress tumor growth by destroying cancer cells or by inhibiting their outgrowth, and it can also promote tumor progression by selecting tumor cells that are better fit to survive in an immunocompetent host or by establishing conditions within the tumor that may facilitate outgrowth.
The immune response against cancer centers on three stages: elimination, equilibrium, and escape. In the absence of complete elimination, persistent immune activation is required to sustain equilibrium between tumor growth and immunity, thereby delaying or preventing disease relapse. However, persisting immune responses are also capable of altering the phenotype of the tumor via a process known as immunoediting. This process has application to the treatment of many cancers, including melanoma.
Developing more effective treatments, including those that target relapses, may center on agents that are able to restart immunotherapy after disease progression to reactivate the primed immune system to recognize and respond to any remaining tumor or tumor cells that have appeared during the tumor escape phase.
One such agent is ipilimumab, a fully human monoclonal antibody. Ipilimumab, unlike chemotherapeutic agents that kill tumor cells by direct cytotoxicity, is known to block cytotoxic T lymphocyte–associated antigen-4 (CTLA-4), thereby potentiating T cell–mediated antitumor immune responses. With that in mind, Robert and colleagues conducted a retrospective study of the use of ipilimumab as retreatment in patients with pretreated advanced melanoma who progressed after initially achieving disease control.
The investigators analyzed the medical records of patients with unresectable stage III or IV melanoma. Patients were previously treated with one or more of the following: dacarbazine, temozolomide, fotemustine, carboplatin, and interleukin-2. Patients received ipilimumab with gp100 peptide vaccine, ipilimumab alone, or gp100 peptide vaccine alone.
The investigators identified 32 patients who met the criteria for consideration in the efficacy analyses. Response rates for the groups receiving ipilimumab with gp100 peptide vaccine or ipilimumab alone were 13.0% and 37.5%, respectively. The disease control rate for the groups receiving ipilimumab with gp100 peptide vaccine or ipilimumab alone were 65.2% and 75.0%, respectively. Of note, 61.3% of patients retreated with ipilimumab survived > 2 years and 6 patients achieved a better response after retreatment than after their original treatment.
There were no new toxicities associated with retreatment with ipilimumab, and toxicities that were seen during initial treatment did not predispose patients to retreatment toxicity.
In closing, this retrospective study demonstrated that the majority of patients with late-stage melanoma who were retreated with ipilimumab achieved durable disease control lasting longer than 2 years. The investigators suggested that if patients meet defined criteria, retreatment with ipilimumab can translate into clinical benefit with no deleterious morbidity.
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- March 25, 2013 at 5:49 pm
Only the abstract is free. Here it is. Full text requires payment. Note that the number of patients in this retrospective study was not large.
Efficacy and Safety of Retreatment with Ipilimumab in Patients with Pretreated Advanced Melanoma who Progressed after Initially Achieving Disease Control
+ Author Affiliations
1Inserm U981, Institut Gustave Roussy
2Dermatology & Skin Cancer, University Hospital Essen
3Research and Development, Bristol-Myers Squibb
4Medical Oncology, Dana-Farber Cancer Inst.
5Melanoma Program, The Angeles Clinic and Research Institute
- ↵* Corresponding Author:
Caroline Robert, Inserm U981, Institut Gustave Roussy, 114 Rue Edouard Vaillant, villejuif, 94805, France caroline.robert@igr.fr
Abstract
Purpose:Ipilimumab is a fully human monoclonal antibody against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) that has been shown to improve survival in patients with pretreated, advanced melanoma in a phase III trial. Some patients in this study who initially responded to ipilimumab treatment but later progressed were eligible for retreatment with their original randomized regimen. Here, outcomes for these patients concerning baseline characteristics, best overall response, and disease control rate, are assessed and considered with respect to the overall study population. Experimental Design:In the phase III study, 676 pretreated patients were randomly allocated to treatment with ipilimumab 3 mg/kg plus gp100 vaccine, ipilimumab 3 mg/kg plus placebo, or gp100 vaccine alone. Of these patients, 32 had a partial or complete objective response or stable disease after treatment and met the eligibility criteria for retreatment, although a total of 40 patients were retreated. Results:Best overall response rates (complete responses plus partial responses) for 31 retreatment-eligible patients in the ipilimumab plus gp100 and ipilimumab plus placebo groups were 3/23 (13.0%) and 3/8 (37.5%), respectively and disease control rates were 65.2 and 75.0%. No new types of toxicities occurred during retreatment and most events were mild-to-moderate. Conclusions: Ipilimumab provided durable objective responses and/or stable disease in qualifying patients who received retreatment upon disease progression with a similar toxicity profile to that seen during their original treatment regimen.
- Received October 23, 2012.
- Revision received January 16, 2013.
- Accepted February 4, 2013.
- Copyright © 2013, American Association for Cancer Research.
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- March 25, 2013 at 5:49 pm
Only the abstract is free. Here it is. Full text requires payment. Note that the number of patients in this retrospective study was not large.
Efficacy and Safety of Retreatment with Ipilimumab in Patients with Pretreated Advanced Melanoma who Progressed after Initially Achieving Disease Control
+ Author Affiliations
1Inserm U981, Institut Gustave Roussy
2Dermatology & Skin Cancer, University Hospital Essen
3Research and Development, Bristol-Myers Squibb
4Medical Oncology, Dana-Farber Cancer Inst.
5Melanoma Program, The Angeles Clinic and Research Institute
- ↵* Corresponding Author:
Caroline Robert, Inserm U981, Institut Gustave Roussy, 114 Rue Edouard Vaillant, villejuif, 94805, France caroline.robert@igr.fr
Abstract
Purpose:Ipilimumab is a fully human monoclonal antibody against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) that has been shown to improve survival in patients with pretreated, advanced melanoma in a phase III trial. Some patients in this study who initially responded to ipilimumab treatment but later progressed were eligible for retreatment with their original randomized regimen. Here, outcomes for these patients concerning baseline characteristics, best overall response, and disease control rate, are assessed and considered with respect to the overall study population. Experimental Design:In the phase III study, 676 pretreated patients were randomly allocated to treatment with ipilimumab 3 mg/kg plus gp100 vaccine, ipilimumab 3 mg/kg plus placebo, or gp100 vaccine alone. Of these patients, 32 had a partial or complete objective response or stable disease after treatment and met the eligibility criteria for retreatment, although a total of 40 patients were retreated. Results:Best overall response rates (complete responses plus partial responses) for 31 retreatment-eligible patients in the ipilimumab plus gp100 and ipilimumab plus placebo groups were 3/23 (13.0%) and 3/8 (37.5%), respectively and disease control rates were 65.2 and 75.0%. No new types of toxicities occurred during retreatment and most events were mild-to-moderate. Conclusions: Ipilimumab provided durable objective responses and/or stable disease in qualifying patients who received retreatment upon disease progression with a similar toxicity profile to that seen during their original treatment regimen.
- Received October 23, 2012.
- Revision received January 16, 2013.
- Accepted February 4, 2013.
- Copyright © 2013, American Association for Cancer Research.
-
- March 25, 2013 at 5:49 pm
Only the abstract is free. Here it is. Full text requires payment. Note that the number of patients in this retrospective study was not large.
Efficacy and Safety of Retreatment with Ipilimumab in Patients with Pretreated Advanced Melanoma who Progressed after Initially Achieving Disease Control
+ Author Affiliations
1Inserm U981, Institut Gustave Roussy
2Dermatology & Skin Cancer, University Hospital Essen
3Research and Development, Bristol-Myers Squibb
4Medical Oncology, Dana-Farber Cancer Inst.
5Melanoma Program, The Angeles Clinic and Research Institute
- ↵* Corresponding Author:
Caroline Robert, Inserm U981, Institut Gustave Roussy, 114 Rue Edouard Vaillant, villejuif, 94805, France caroline.robert@igr.fr
Abstract
Purpose:Ipilimumab is a fully human monoclonal antibody against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) that has been shown to improve survival in patients with pretreated, advanced melanoma in a phase III trial. Some patients in this study who initially responded to ipilimumab treatment but later progressed were eligible for retreatment with their original randomized regimen. Here, outcomes for these patients concerning baseline characteristics, best overall response, and disease control rate, are assessed and considered with respect to the overall study population. Experimental Design:In the phase III study, 676 pretreated patients were randomly allocated to treatment with ipilimumab 3 mg/kg plus gp100 vaccine, ipilimumab 3 mg/kg plus placebo, or gp100 vaccine alone. Of these patients, 32 had a partial or complete objective response or stable disease after treatment and met the eligibility criteria for retreatment, although a total of 40 patients were retreated. Results:Best overall response rates (complete responses plus partial responses) for 31 retreatment-eligible patients in the ipilimumab plus gp100 and ipilimumab plus placebo groups were 3/23 (13.0%) and 3/8 (37.5%), respectively and disease control rates were 65.2 and 75.0%. No new types of toxicities occurred during retreatment and most events were mild-to-moderate. Conclusions: Ipilimumab provided durable objective responses and/or stable disease in qualifying patients who received retreatment upon disease progression with a similar toxicity profile to that seen during their original treatment regimen.
- Received October 23, 2012.
- Revision received January 16, 2013.
- Accepted February 4, 2013.
- Copyright © 2013, American Association for Cancer Research.
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