Go To Main TNBC Website


  New Posts New Posts RSS Feed - Immune Therapy to Fight Cancer
  FAQ FAQ  Forum Search   Events   Register Register  Login Login

Immune Therapy to Fight Cancer

 Post Reply Post Reply Page  <1234>
Author
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jan 26 2015 at 8:20pm
Lillie,

Thanks so much for sharing!  Yervoy's clinical name is ipilimumab.  Hope it proves useful as a targeted therapy for TNBC.  


The first immune-checkpoint inhibitor to be tested in a clinical trial was ipilimumab (Yervoy, Bristol-Myers Squibb), an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) mAb. CTLA-4 belongs to the immunoglobulin superfamily of receptors, which also includes programmed cell death protein 1 (PD-1), B and T lymphocyte attenuator, T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and V-domain immunoglobulin suppressor of T cell activation. In 2011, the US Food and Drug Administration approved the use of ipilimumab in patients with metastatic melanoma, either as initial therapy or after relapse.
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
tripleneg-mom View Drop Down
Groupie
Groupie
Avatar

Joined: Jan 21 2015
Location: Texas
Status: Offline
Points: 55
Post Options Post Options   Thanks (0) Thanks(0)   Quote tripleneg-mom Quote  Post ReplyReply Direct Link To This Post Posted: Jan 29 2015 at 4:50pm
Wow Lillie, that's amazing.  I wonder what is behind the decision to try to get the lady Yervoy vs the Nivolumab (its the anti PD-1), also by Bristol-Meyers.  There's a study that is actually trying these 2 together, and includes TNBC in the criteria.  MD Anderson (where I go) is one of the locations, but the magic gatekeeper has those gates closed for some reason.

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Mar 01 2015 at 11:28am
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Mar 01 2015 at 1:52pm

New test predicts a woman's chance of surviving breast cancer: Images track hotspots in tumours where the immune system attacks disease cells


  • Test tracks how strongly the immune system is working to control tumours
  • Location of immune cell clusters is 'as important as the number of cells'  
  • Test analyses images, checking cells are well-placed to attack cancer
  • Those at low risk survived 50 per cent longer before the cancer spread 


Read more: http://www.dailymail.co.uk/health/article-2972285/New-test-predicts-woman-s-chance-surviving-breast-cancer-Images-track-disease-hotspots-body-reveal-progression.html#ixzz3TA501EmY 

DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Mar 10 2015 at 8:18am
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Apr 16 2015 at 1:24pm

Roche to Skip Ahead to Late-Stage Study for Breast Cancer Drug

Roche Holding AG will skip a mid-stage study of an experimental immunotherapy for breast cancer and proceed directly to a phase 3 trial later this year. 

The Swiss company will study MPDL3280A for triple-negative breast cancer, which is currently treated mostly with chemotherapy, spokeswoman Holli Dickson said in a phone interview. The drug will be tested in combination with chemotherapy.

http://www.swissinfo.ch/eng/roche-to-skip-ahead-to-late-stage-study-for-breast-cancer-drug/41384180


DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
kellly View Drop Down
Groupie
Groupie
Avatar

Joined: Jul 25 2008
Location: Netherlands
Status: Offline
Points: 64
Post Options Post Options   Thanks (0) Thanks(0)   Quote kellly Quote  Post ReplyReply Direct Link To This Post Posted: Apr 17 2015 at 8:23am
very promising.
DX '08,34yr, TN-IBC, gr3, 4 FEC, 3 Taxotere, biMST ->3/9 nodes+, 23rad's, BRCA-, bi DIEP '09. '12 son born!
Dx2 feb'14 mets subcl. & mediast. lymph nodes.CHEK2-. Olaparib, Carboplatin. Now: Nivolumab
Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Apr 20 2015 at 11:19pm
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: May 27 2015 at 8:26am
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
kellly View Drop Down
Groupie
Groupie
Avatar

Joined: Jul 25 2008
Location: Netherlands
Status: Offline
Points: 64
Post Options Post Options   Thanks (0) Thanks(0)   Quote kellly Quote  Post ReplyReply Direct Link To This Post Posted: May 28 2015 at 5:27am
very exciting !
Thanx for posting Donna,
i am trying to get in a trial checkpoint inhibitor trial, but havent been succesful yet. 
DX '08,34yr, TN-IBC, gr3, 4 FEC, 3 Taxotere, biMST ->3/9 nodes+, 23rad's, BRCA-, bi DIEP '09. '12 son born!
Dx2 feb'14 mets subcl. & mediast. lymph nodes.CHEK2-. Olaparib, Carboplatin. Now: Nivolumab
Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: May 30 2015 at 2:48pm
TESARO and Merck to Collaborate on a Combination Study of Niraparib and KEYTRUDA(R) (Pembrolizumab)

Clinical Trial Will Evaluate TESARO's PARP Inhibitor With Merck's anti-PD-1 Therapy in Patients With Breast and Ovarian Cancers

To evaluate the combination of TESARO's niraparib plus Merck's anti-PD1 therapy, KEYTRUDA® (pembrolizumab), in a Phase 1/2 clinical trial.

This trial is planned to evaluate the preliminary safety and efficacy of niraparib plus KEYTRUDA in patients with triple negative breast cancer or ovarian cancer. This trial will be conducted by TESARO and Merck, through a subsidiary, and is expected to begin by the end of 2015.

"The combination of a PARP inhibitor and anti-PD-1 antibody in this study has the potential to build upon the responses already observed with each of these compounds as monotherapies," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "Treatment options for patients with triple negative breast cancer are extremely limited, and we look forward to assessing this exciting new approach."

http://globenewswire.com/news-release/2015/05/30/740632/10136643/en/TESARO-and-Merck-to-Collaborate-on-a-Combination-Study-of-Niraparib-and-KEYTRUDA-R-Pembrolizumab.html
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: May 31 2015 at 12:07pm
Genentech's PD-L1 breakthrough star 'atezo' positioned to vault ahead on cancer
MPDL3280A--it's atezolizumab now, or just "atezo" 

"Behind the headline presentations here at ASCO, you'll find one of the biggest players in immuno-oncology quietly positioning itself to vault into a leading role in the fast-emerging market, using its in-house technology to best identify the patients most likely to respond to their checkpoint inhibitor and then rapidly exploiting that edge with a full slate of combination therapies matched to their lead program. 


Genentech arrived at ASCO with a new name for MPDL3280A--it's atezolizumab now, or just "atezo" for shorthand--which is in 10 Phase III studies (an 11th is being readied) amid a blizzard of 36 clinical trials. An abstract to be posted here at ASCO points to newly identified subpopulations of lung cancer patients who may turn out to be ideally suited to atezo, which has "breakthrough" status at the FDA as regulators appear eager to approve these new drugs.


There's also an intriguing experimental treatment now in Phase I--the "anti-CEA" RG7802 program--that promises to add a brand new T cell approach to fighting cancer that is being lined up for a combo approach with atezo. Investigators are using bispecific antibody technology to direct a T cell attack directly against the CEA antigen that clusters on the surface of cancer cells. And Dan Chen, Genentech's global development team leader for immuno-oncology, says using that in combination with atezo "makes total sense."

Susan Zager's insight:

According to Chen, "The bispecific antibody RG7802 treatment is "similar to but different from CAR-T," referring to the hot new field that reengineers T cells with a chimeric antigen receptor to direct an attack against cancer cells. In this case, Genentech has designed a bispecific antibody that attaches to cancer cells as well as T cells. T cells that would normally be circulating in search of an invader like the flu are redirected to attack cancer cells. In preclinical studies, he says, it has looked like one of the most potent cancer therapies he's seen. 

In Chen's view of the next few years, the development of their checkpoint inhibitors will move past chemotherapy combinations to new approaches that involve a big step up through the use of more innovative matchups, with pipeline agents coming in to amp up impact. Roche has also paired itself with immatics biotechnologies, a German biotech that's been working on new cancer vaccines. And there's an anti-OX40 approach that stimulates the production of T cells.

http://www.scoop.it/t/breast-cancer-news


http://www.fiercebiotech.com/story/genentechs-pd-l1-breakthrough-star-atezo-positioned-vault-ahead-cancer/2015-05-30

DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Sep 03 2015 at 7:31pm
The inhibition of CDK 4/6 and PD-1 represent two of the most exciting developments in the field of metastatic breast cancer. Following an accelerated approval in February 2015, the CDK4/6 inhibitor palbociclib (Ibrance) has continued to make headlines as an exciting new agent for patients with HR-positive metastatic breast cancer. Additionally, PD-1 and PD-L1 inhibitors have shown early signs of promise for patients with metastatic triple-negative breast cancer (TNBC).

The phase II PALOMA-1 trial,1 which was the basis for the approval of palbociclib, found that the novel CDK 4/6 inhibitor in combination with letrozole (Femara) reduced the risk of disease progression by 51% compared with letrozole alone. The median progression-free survival (PFS) with palbociclib was 20.2 versus 10.2 months for letrozole alone (HR, 0.488; P = .0004).

At the 2015 ASCO Annual Meeting, the PALOMA-3 trial found that palbociclib plus fulvestrant (Faslodex) improved PFS compared with fulvestrant alone in women with HR-positive, HER2-negative metastatic breast cancer following progression on prior endocrine therapy.2 At the time of the interim analysis, the median PFS was 9.2 months for palbociclib plus fulvestrant and 3.8 months for placebo plus fulvestrant (HR, 0.422; 95% CI, 0.318-0.560; P <.0001).

In addition to this now FDA-approved approach, two early phase clinical trials have shown potential for PD-1/PD-L1 inhibition in pretreated patients with TNBC. In the KEYNOTE-012 trial,3 pembrolizumab demonstrated an overall response rate (ORR) of 18.5%. In a similar patient population, the PD-L1 inhibitor atezolizumab showed an ORR of 19%.4 Larger trials are now looking to confirm these findings. - See more at:
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Sep 20 2015 at 8:52pm
http://www.mdanderson.org/publications/oncolog/previous-issues/2015-july/immunotherapy-trials-offer-hope-to-patients-with-high-risk-or-metastatic-breast-cancer.html

Triage Program for Triple-Negative Breast Cancer

Triple-negative breast cancers—those that do not express estrogen receptors, progesterone receptors, or HER2—have about a 50% chance of responding to standard neoadjuvant chemotherapy. For patients whose cancer does not respond and who therefore are at higher risk for recurrence, researchers at MD Anderson Cancer Center have developed a triage program to find an appropriate experimental treatment.

At MD Anderson, patients with triple-negative breast cancer undergo genomic testing and then begin standard neoadjuvant chemotherapy. Dr. Litton said the triage program is similar in design to the I-SPY 2 TRIAL (see Novel Trial Design Streamlines Development of Breast Cancer TherapiesOncoLog, April 2015), except that patients begin treatment right away instead of waiting 2–3 weeks for the results of the genomic tests. When the results arrive, physicians also have clinical data that indicate whether the cancer is responding to standard chemotherapy.

“In the triage protocol, we can look at the early response and, for patients whose cancer is responding, we continue standard therapy and observe them; these patients will likely do well,” Dr. Litton said. “But we know that patients whose cancer does not respond to those initial doses of first-line treatment have only a 5% chance of a complete pathologic response to standard second-line treatment, and these patients are assigned to a clinical trial based on the results of the genomic tests. We’re in the process of opening a series of phase II trials of new treatments—including immunotherapy—for triple-negative breast cancer.”

Dr. Litton said that MD Anderson is the only institution in the United States to offer such a program for patients with triple-negative breast cancer.

DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Sep 20 2015 at 8:54pm
Immunotherapy Trials Offer Hope to Patients with High-Risk or Metastatic Breast Cancer

Although the cure rate for breast cancer has risen steadily in recent decades, recurrent or metastatic disease remains difficult to control. To fight metastatic breast cancer and forestall the recurrence of high-risk primary disease, researchers at The University of Texas MD Anderson Cancer Center are using various techniques to boost the body’s immune system. Clinical trials of many of these therapies are already under way.

Graph

Patients with metastatic breast cancer treated with standard chemotherapy followed by the STn-KLH vaccine who also received endocrine therapy (tamoxifen) had a longer median overall survival than did those treated with standard chemotherapy followed by a control vector. Adapted from Ibrahim NK, et al. J Cancer 2013;4:577–584.

Recent research findings have sparked interest in the role of immunotherapy in breast cancer treatment, said Elizabeth Mittendorf, M.D., Ph.D., an associate professor in the Department of Surgical Oncology. “For a very long time, breast cancers were not thought to be immunogenic,” she said. “But data published in the past 2 years have shown that there are immune cells, including T cells, in breast tumors. This suggests that breast tumors are indeed immunogenic.”

Breakthroughs in immunotherapy against other types of cancer have encouraged research of its use against breast cancer. “The understanding of immunology in cancer is progressing very fast,” said Nuhad Ibrahim, M.D., a professor in the Department of Breast Medical Oncology. Citing the recent successes of immunotherapy drugs and vaccines in melanoma and prostate cancer, Dr. Ibrahim said, “In breast cancer we still have not had those kinds of breakthroughs, but there are definitely leads.”

Those leads have encouraged researchers to explore multiple avenues. “As much as we’ve always been fascinated with pushing the immune system, there has never been enough response to older immunotherapies, like interferon or interleukin-2, to benefit breast cancer patients,” said Debu Tripathy, M.D., a professor in and chair of the Department of Breast Medical Oncology. But with advances in therapeutic vaccines, immune checkpoint inhibitors, and other immunotherapies, he said, “We’ve finally crossed that threshold.”

Vaccines

Anti-MUC1 vaccines

“The early studies of immunotherapy with vaccines in patients with metastatic breast cancer did not meet their primary objective of improving overall survival, but we learned a lot from these studies,” said Dr. Ibrahim, who in the 1990s—along with James Murray III, M.D., a professor in the Department of Breast Medical Oncology—led a randomized trial of the sialyl-Tn–keyhole limpet hemocyanin (STn-KLH; also called Theratope) vaccine. The STn-KLH vaccine was derived from MUC1, a mucin expressed on the surface of a large proportion of breast cancer cells. The study did not meet its goal of extending progression-free survival for patients with metastatic breast cancer. However, in a post hoc analysis, the vaccine appeared to improve survival outcomes for patients who had previously been treated with tamoxifen.

Dr. Ibrahim, in collaboration with the U.S. National Cancer Institute, recently completed a trial of an anti-MUC1, anti–carcinoembryonic antigen vaccine combined with costimulatory molecules and given with docetaxel. The study’s report is under peer review.

OPT-822

OPT-822 is a carbohydrate vaccine similar in structure to the STn-KLH vaccine. Early studies of OPT-822 demonstrated prolonged overall survival in a subset of patients with metastatic breast cancer, especially when patients received low-dose cyclophosphamide. These findings led to a multicenter trial that recently completed enrollment. Dr. Murray is MD Anderson’s principal investigator for the trial, in which patients with metastatic breast cancer received low-dose cyclophosphamide with the OPT-822 vaccine along with the lipid adjuvant OPT-821 or placebo. The results are currently being analyzed.

E75

Of the breast cancer vaccines, the farthest along is E75 (nelipepimut-S, NeuVax), a peptide vaccine that is derived from human epidermal growth factor receptor 2 (HER2). Dr. Murray led a small phase I clinical trial of E75 combined with granulocyte-macrophage colony-stimulating factor (GMCSF) in patients with metastatic breast or ovarian cancer. Although HER2-specific immune responses were generated in most patients, no antitumor responses were observed, possibly because of the large tumor burden in the population studied.

“A general consensus at MD Anderson is that for vaccines to be successful against breast cancer, they need to be given in patients with low-volume disease, and that means giving them in the adjuvant therapy rather than the metastatic disease setting,” said Dr. Mittendorf, who also served as a principal investigator of early trials of the E75 vaccine.

Dr. Mittendorf is now the principal investigator of two multicenter trials of the E75 vaccine as adjuvant therapy for patients with HER2-positive breast cancer at high risk for recurrence: a phase III trial that has completed enrollment and a phase II trial of the vaccine plus trastuzumab that is currently enrolling patients.

GP2 and AE37

Two other HER2-derived peptide vaccines, GP2 and AE37, are under investigation as adjuvant therapy in an ongoing study that has completed enrollment. The GP2 vaccine—which resulted from research led by George Peoples Jr., M.D., an adjunct professor in the Department of Surgical Oncology—has greater immunogenicity than E75 and binds to both human leukocyte antigen (HLA)-A2 and HLA-A3. AE37 contains more than 10 amino acids, allowing for a broad range of immune stimulation in patients. AE37 was shown in preclinical studies to significantly enhance HER2-specific CD4-positive “helper” T cells.

Patients included in the ongoing adjuvant therapy study had a high risk for recurrence because of lymph node involvement or other factors such as high levels of HER2 expression; however, patients with HER2 immunohistochemistry scores indicating HER2-negative or borderline status were also included in the study. Because the two vaccines bind to different major histocompatibility complex class molecules, patients in the study were sorted according to their HLA status before randomization. Those who were positive for HLA-A2/A3 were randomly assigned to receive GM-CSF with or without GP2; those who were negative for HLA-A2/A3 were randomly assigned to receive GM-CSF with or without AE37.

Dr. Mittendorf presented the primary analyses of the study’s GP2 and AE37 arms in 2014 at the American Society of Clinical Oncology’s Breast Cancer Symposium and its Annual Meeting, respectively. “Both vaccines were safe and stimulated an immune response,” Dr. Mittendorf said. “AE37 had its strongest efficacy in patients with triple-negative breast cancer, and we’re developing a trial of the vaccine for these patients. GP2 had its strongest signal in HER2-positive patients who had received trastuzumab.”

E39 and J65

The E39 vaccine is derived from folate binding protein, which is expressed on the surface of most breast and ovarian cancer cells. Studies performed at MD Anderson demonstrated that E39 produced a robust immune response in ovarian cancer patients; however, whether this response would exhaust the immune system and prove counterproductive was not known. To determine the optimal strategy for using the vaccine, Dr. Mittendorf and her colleagues have begun a clinical trial at MD Anderson in which patients with breast or ovarian cancer receive E39 and J65, an attenuated version of E39, on various dosing schedules. Patients are randomly assigned to receive monthly injections according to one of three regimens: six injections of E39, three injections of E39 followed by three of J65, or three injections of J65 followed by three of E39.

“This trial will determine whether it’s better to come in hard with E39 for a few doses and then give J65 to soften the blow or start soft with J65 and ramp up slowly to E39,” Dr. Mittendorf said.

Immune checkpoint inhibitors

The relatively new class of drugs that inhibit immune checkpoints—cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and the PD-1 ligand (PD-L1)—has extended survival for patients with metastatic melanoma and has been found to be effective against several other types of cancer, including breast cancer.

Jennifer Litton, M.D., an associate professor in the Department of Breast Medical Oncology, has been an investigator on early trials of anti–PD-1 and anti–PD-L1 antibodies as well as two trials combining an anti–CTLA-4 antibody with an anti–PD-1 antibody in patients with metastatic breast cancer. “We didn’t see the huge numbers of responses we’ve seen with other breast cancer therapies, but the few patients who did respond had long-lasting responses,” Dr. Litton said. “In several national trials, we’ve had people with triple-negative breast cancer whose responses have lasted for years. That’s the game-changer.”

The responses to checkpoint inhibitors in patients with triple-negative breast cancer are particularly encouraging, Dr. Tripathy said, because these patients have limited treatment options. Triple-negative breast cancers tend to have more genetic mutations than do other breast cancer subtypes, and these mutations generate abnormal or overexpressed proteins that may present targets for immunotherapy. For example, a recent study by Drs. Mittendorf and Litton and their colleagues found that 20% of triple-negative breast cancers expressed PD-L1. “Triple-negative breast cancer may be a little more immunogenic than other subtypes,” Dr. Tripathy said, “and that may be an opportunity.”

Dr. Litton agreed. “Almost all of the checkpoint inhibitor trials we have in the planning stages are for patients with triple-negative breast cancer,” she said. Although most of these trials are for patients with metastatic disease, researchers are eager to learn whether checkpoint inhibitors can play a role in other settings.

Of particular interest is a clinical trial of the anti–PD-L1 antibody MPDL3280A with nanoparticle albumin-bound paclitaxel in patients with triple-negative breast cancer that did not respond to initial standard neoadjuvant treatment. Dr. Litton, the trial’s principal investigator, said the trial is part of a new MD Anderson program to identify patients whose cancer does not respond to standard chemotherapy and offer alternative treatments (see Triage Program for Triple-Negative Breast Cancer, below).

Researchers are also planning a large trial of the anti–PD-1 antibody pembrolizumab as adjuvant therapy in patients with triple-negative breast cancer who have residual tumor cells in the breast or lymph nodes after neoadjuvant chemotherapy. “These patients have a higher risk of developing metastatic disease and dying of their disease later,” Dr. Tripathy said. Patients in the study will be randomly assigned to standard follow-up care with or without pembrolizumab.

In addition, a clinical trial of pembrolizumab will soon begin enrolling patients with inflammatory breast cancer, which is uncommon but aggressive. The trial, which aims to determine whether pembrolizumab can sustain the antitumor immune response started by standard-of-care chemotherapy, is led by Naoto Ueno, M.D., Ph.D., a professor in the Department of Breast Medical Oncology and executive director of the Morgan Welch Inflammatory Breast Cancer Program.

Although the survival effects of checkpoint inhibitors in breast cancer patients remain largely unknown, Dr. Litton is optimistic. “I think we’re only scratching the surface,” she said. “I think we’re going to see combinations of different immunotherapies as well as how to trigger an immune response in a greater percentage of breast cancer patients.”

Other immunotherapy approaches

“Our immunotherapy studies have moved from just vaccines to include checkpoint inhibitors and other immunotherapy strategies,” Dr. Mittendorf said. “And as an institution, we have the opportunity to do more.”

For example, Dr. Ibrahim is the principal investigator at MD Anderson for an ongoing multi-institutional trial of the oral immunostimulant indoximod with taxane-based chemotherapy for patients with HER2-negative metastatic breast cancer. Indoximod inhibits the indoleamine 2,3-dioxygenase pathway, which suppresses T cell activity.

Also under investigation are agents that block the action of interleukin-8 (CXCL8), which has an immunomodulatory effect and is associated with breast cancer growth and metastasis. A trial of one such agent, reparixin, which binds to the CXCL8 receptor CXCR1, is underway at MD Anderson and other institutions.

Preclinical studies of promising therapies also are underway. For example, Dr. Mittendorf said, Laurence Cooper, M.D., Ph.D., a professor in the Division of Pediatrics, is investigating the use of T cells modified with chimeric antigen receptors (see “Sleeping Beauty” Technique Modifies T Cells to Treat B Cell MalignanciesOncoLog, May 2014) against triple-negative breast cancer.

Also on the horizon are studies of antiphosphatidylserine antibodies, which have been shown to improve the activity of taxanes against breast cancer. Likewise, studies are being planned of agents that stimulate the activity of natural killer cells and therefore may enhance the response to standard breast cancer drugs such as trastuzumab and toll-like receptor agonists.

Looking ahead

As researchers continue to elucidate the role of immunotherapy against breast cancer, clinical trials are increasingly becoming available for patients with metastatic disease and those with difficult-to-treat subtypes at high risk of recurrence. “There are trials that are open or in the process of opening for patients with triple-negative breast cancer,” Dr. Tripathy said. “The field is moving rapidly, and we hope that immunotherapy can prevent recurrences.”

For more information, contact Dr. Nuhad Ibrahim at 713-792-2817, Dr. Jennifer Litton at 713-792-2817, Dr. Elizabeth Mittendorf at 713-792-2362, Dr. James Murray at 713-792-2817, or Dr. Debu Tripathy at 713-792-2817. To learn more about ongoing clinical trials at MD Anderson for patients with breast cancer, visitwww.clinicaltrials.org.


http://www.mdanderson.org/publications/oncolog/previous-issues/2015-july/immunotherapy-trials-offer-hope-to-patients-with-high-risk-or-metastatic-breast-cancer.html

DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Oct 08 2015 at 11:14am
The drug, called Atezolizumab, is a form of immunotherapy, a new treatment option for patients with some types of lung cancer, bladder cancer and melanoma. Based on early data from a clinical trial, the treatment, which helps the immune system fight cancer, looks promising for women with metastatic, triple-negative breast cancer.

To read the entire article about the research at John Hopkins:

http://www.baltimoresun.com/health/breastcancer/bs-hs-triple-negative-breast-cancer-drugs-20151007-story.html
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Oct 09 2015 at 8:55am
A Study of Atezolizumab (MPDL3280A) in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Patients With Previously Untreated Metastatic Triple Negative Breast Cancer (IMpassion130)

DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
mhurt84 View Drop Down
Newbie
Newbie
Avatar

Joined: Aug 19 2015
Location: new york
Status: Offline
Points: 10
Post Options Post Options   Thanks (0) Thanks(0)   Quote mhurt84 Quote  Post ReplyReply Direct Link To This Post Posted: Nov 06 2015 at 11:10am
Hi everyone,
Just checking in. Last time I posted a few things happened. Mom originally enrolled in a clinical trial using Taxol + Cobimetinib (MEK inhibitor) but had a solitary brain met diagnosed so she was taken off the trial (a few days without no active brain lesions was an inclusion criteria). Long story short she got SRS right away and instead a week later enrolled in this phase 3 trial you mentioned above of MPDL3280A/placebo +Abraxane.
 
End of the month will be her follow up scan to decide where we go from here..see how she is responding to therapy. Her oncologist is very aware that this is a randomized placebo controlled trial and he's blinded as to whether she is getting the immunotherapy. He plans to see the results of the 8 week follow up trial CT scan and go from there.
I was wondering if anyone else is on an immunotherapy? What are your side effects??
 
Mom is getting the typical side effects of Abraxane (mild neuropathy/fatigue/hair loss)
but she has itchy eyes/sandy eyes, not sure if that could be the immunotherapy.
 
This can be a bit nerve wrecking not knowing if she is actually getting the immunotherapy, also who knows if it would even work. There is a lot of promise but still under investigation...
 
Pembrolizumab (Keytruda) is the other immunotherapy opening up as monotherapy soon also for metastatic TNBC patients. My moms oncologist has mentioned this to me. He has this in mind if we come to find out that she could indeed be on placebo/not MPDL3280a and there is any sign of progression, he can unblind himself...
 
I know she is still getting standard of care with Abraxane and have read some ladies that this therapy has conrolled/brought them to NED.
 
Thats what I am praying for <3!!
 
Just wanted to see if others out there are on these immunotherapies (Nivolumab/Pembrolizumab/MPDL now called Azetolizumab)? share your experiences...
I dont see much post about it and would love to share her experience with others...
 
Thank you!!!
God bless you all <3


Edited by mhurt84 - Nov 06 2015 at 11:17am
Daughter-Mom w/ TNBC 9/15 mets to lungs and bones-Dx 2011 TNBC stage IIA s/p MX, Chemo (ACT), Radiation.
" Trust in the Lord with all your heart..acknowledge him..and he shall direct your paths"
Back to Top
gordon15 View Drop Down
Senior Member
Senior Member


Joined: Jun 22 2015
Location: San Diego CA
Status: Online
Points: 749
Post Options Post Options   Thanks (0) Thanks(0)   Quote gordon15 Quote  Post ReplyReply Direct Link To This Post Posted: Nov 06 2015 at 2:08pm
I can't help with any immuneotherapy but my wife had itchy eyes after finishing her Carboplatin/Gemzar chemo & her PCP is treating as "pink eye" and gave her drops yesterday fyi the Rx is antibiotic drops called Ciprofloxacin Hydrochloride.


Edited by gordon15 - Nov 06 2015 at 2:16pm
Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 12578
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: May 03 2016 at 10:34pm
Keytruda - Pembrolizumab Promising in Metastatic Triple-Negative Breast Cancer

Results from a phase Ib trial suggest that the programmed death 1 (PD-1) inhibitor pembrolizumab has activity and an acceptable toxicity profile as single-agent therapy in heavily pretreated, advanced triple-negative breast cancer (TNBC). 

“TNBC tumors are frequently of high histological grade, present at an advanced stage, are typically more aggressive and difficult to treat than hormone receptor–positive tumors, and are associated with a higher risk of early relapse,” wrote study authors led by Rita Nanda, MD, of the University of Chicago. “Given the suboptimal outcomes with chemotherapy, new targeted therapies for TNBC are urgently needed.”

Previous research has suggested that immunotherapy may provide benefit in TNBC. The new study, called KEYNOTE-012, was a nonrandomized phase Ib trial of pembrolizumab, which included a number of malignancies; this analysis focused on the 32 TNBC patients who were positive for the PD-1 ligand PD-L1. The results were published in the Journal of Clinical Oncology.

This was a heavily pretreated population, with 46.9% of patients having received at least three lines of therapy for metastatic disease, and 25.0% having received at least five lines. The median age in the study was 50.5 years.

Of the 32 patients included, 37.5% experienced some decrease in tumor burden from baseline. Twenty-seven of the patients met protocol-specified inclusion criteria for the efficacy analysis, and in those patients the overall response rate was 18.5%. One patient (3.7%) had a complete response, four had a partial response (14.8%), seven had stable disease (25.9%), and 13 patients had progressive disease (48.1%). The overall disease control rate (complete or partial response or stable disease for at least 24 weeks) was 25.9%.

Most patients (56.3%) experienced some treatment-related toxicity, and 15.6% had at least one grade 3 or higher adverse event (AE). The most common treatment-related AEs were arthralgia (18.8%), fatigue (18.8%), myalgia (18.8%), and nausea (15.6%). The grade 3 AEs included anemia, aseptic meningitis, lymphopenia, headache, and pyrexia. One patient died due to a treatment-related AE, a combination of disseminated intravascular coagulation and grade 4 decreased blood fibrinogen. Onset of this event occurred 10 days after the initial pembrolizumab dose.

The authors found that there was evidence of increasing probability of response with pembrolizumab with increasing expression of PD-L1, but they noted the small population size limits that finding’s significance. The 18.5% overall response rate was similar to other subsets of the KEYNOTE-012 study, including head and neck cancer patients (21.4%) and gastric cancer patients (22.2%).

“Overall, these results support further development of pembrolizumab for the treatment of metastatic TNBC,” the authors concluded. A phase II trial (KEYNOTE-086) is currently enrolling TNBC patients to test this therapy, and other studies that will combine the PD-1 inhibitor with other therapies are also in development.


http://www.cancernetwork.com/breast-cancer/pembrolizumab-promising-metastatic-triple-negative-breast-cancer


DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
 Post Reply Post Reply Page  <1234>
  Share Topic   

Forum Jump Forum Permissions View Drop Down

Forum Software by Web Wiz Forums® version 11.05
Copyright ©2001-2016 Web Wiz Ltd.