SABCS 2018 Update
by Guest Blogger, Anne Loeser
Great News! As opposed to several years ago when only sparse information about MBC was available at SABCS, this year it appeared that nearly half of the studies pertained to metastatic (as opposed to early stage) breast cancer.
I have incorporate the notes below into my book, “The Insider's Guide to Metastatic Breast Cancer,” which Komen Greater NYC has graciously hosted on their website. { 2/20/19 Update: Now available in eBook and paperback at Amazon! }
Notes Summary (please see the complete notes for more details):
Considerable research regarding immunotherapy as a type of treatment for MBC, especially with regard to TNBC.
Substantial research is underway regarding targeted therapies based upon biomarkers. Some of the results are provided below.
Biomarkers are being increasingly used as eligibility criteria for specific therapies, and as measurements of response to treatment.
It may take quite a while for treatment results to surface with regard to CDK4/6 inhibitors!
Dr. Nikhil Wagle (Medical Oncologist @ Dana Farber, and Director of the MBC Project): “DNA sequencing does not tell the whole story” because it excludes:
RNA expression
Protein characteristics
Epigenics
The microenvironment/immune cell expression
Dr. Roisin M. Connolly (Johns Hopkins School of Medicine): There are two potential clinical pathways for treating TNBC MBC:
If tumor is PDL-1 positive: the patient should ideally receive Atezolizumab with Abraxane (IMPassion130 trial, median Overall Survival (OS) on the combination was 25 months vs. 15.5 months on Abraxane alone. Combination is not yet FDA-approved as of Dec. 2018.)
If tumor is PDL negative, or the patient cannot obtain the above drug combination: Sequential single agent chemotherapy is recommended. Combination chemotherapy should only be given in the event of visceral crisis (severe organ dysfunction).
After the above, if the patient has a germline BRCA mutation, Talazoparib or Olaparib can be given.
Research is increasingly underway on the subset of MBC patients who are both Hormone Receptor (HR) positive and HER2 positive, sometimes referred to as “Triple Positive.”
Loss of function of NF1 (“neurofibromatosis type 1”), a tumor suppressor gene product, is a marker of acquired resistance to endocrine therapy specific to lobular bc patients.
Talazoparib (Talzenna) and Olaparib (Lynparza) were both FDA-approved in 2018 for HER2 negative MBC patients with germline BRCA1 or BRCA2 mutations.
Oral SERDs and oral SERMs are being studied, including GDC9545, SAR439859, RAD1901, LSZ102, and ZN-C5.
At least two new classes of drugs are currently being studied in MBC:
SERCAs (Selective Estrogen Receptor Covalent Antagonists)
BCL-2 Inhibitors
MBC studies based upon mutations:
PIK3CA Mutations in pre-treated Hormone Receptor+/HER2- Patients
HER2 or HER3 Mutations in Hormone Receptor Positive Patients
Olaparib (a PARP inhibitor) is being studied in combination with Durvalumab (“Imfinzi”), a PD-L1 inhibitor, in HER2 negative MBC patients with BRCA1 or BRCA2 germline mutations in the Mediola study.
A study for HER2 positive, Hormone Receptor negative MBC patients: PATRICIA Phase 2 study
HR+/HER2- Patients with Visceral Disease: It is noteworthy that Kisqali plus endocrine therapy appears to be highly effective for MBC patients with HR+/HER2- visceral disease.
Kisqali dose reduction: A study of patients experiencing adverse effects in the MONALEESA program of Kisqali indicated that dose reductions from the prescribed 600mg daily to 400mg daily and even 200mg daily did not compromise response to treatment, and most patients needed only one dose reduction to relieve their symptoms.
Treatments being studied for Hormone Receptor+/HER2+ (“Triple Positive”) MBC patients:
Aromatase Inhibitor + Herceptin (Trastuzumab) + Pertuzumab (Perjeta)
Aromatase Inhibitor + Herceptin (Trastuzumab) + Lapatinib (Tykerb)
Ibrance and Herceptin, with or without Letrozole
Treatments Being Studied for TNBC MBC patients:
The Phase 3 IMPassion130 trial
The combination of Keytruda (Pembrolizumab) and Zejula (Niraparib) has shown promising and durable response rates
Study of HER3 Overexpressed MBC Patients
About Anne Loeser:
After launching a career as a Social Worker in NYC, Anne relocated to Chicago where she unexpectedly found herself being trained in a totally unrelated field as a computer programmer. Anne eventually moved into Project Management where she was responsible for multi-million dollar initiatives that were implemented in the US and overseas. When she was diagnosed with Stage II breast cancer in 1993 after four years of misdiagnosis, Anne took a 6-month hiatus from work to undergo a double mastectomy and chemotherapy. After returning to work she remained diligent about follow-up exams, all of which were normal.
In 2007 Anne experienced a dry hacking cough which physicians misdiagnosed as GERD and post nasal drip. Over the next several years her cough worsened and she began losing weight. In 2011, she became hoarse to the point that her voice could barely be heard, and a specialist discovered that one of her vocal cords was paralyzed. Further tests revealed lesions on her lung, malignant pleural effusion, and malignant pericardial effusion as a consequence of metastatic breast cancer (mbc), which had been misdiagnosed from 2007 - 2011.
After eight years of misdiagnosis - four for her early stage breast cancer and another four for mbc - Anne recognized that it was imperative to become knowledgeable about mbc and its treatments in order to attain the best possible medical outcome. Furthermore, she felt an overwhelming desire to become an advocate for herself and others in order to maximize the chances of medical success for all patients living with the disease.
To this end, Anne began researching therapies for her own hormone receptor positive, HER2 negative disease, and subsequently broadened her research to explore conventional and complementary treatment options for all mbc subtypes. In 2015, Anne introduced her book, “The Insider's Guide to Metastatic Breast Cancer” which she continually updates and has forwarded free of charge to more than 3,000 patients and caregivers worldwide. She cherishes the 19 pages of feedback received from her readers, which are summarized in this patient's response: “Your guidebook is absolutely helpful. I read it on a regular basis. All the recommendations have helped me survive.”
In addition to her book, Anne has published several commentaries and is the co-author of a peer-reviewed article about Atypical Patient Response.
Anne resides in Salt Lake City with her husband Steve and talkative parrot Pumpkin, and is currently debating about how best to respond to Pumpkin's oft-repeated invitation, “Marry me!”
