ASCO 2019 Preliminary MBC Findings

Bestbird

The annual American Society of Clinical Oncology (ASCO) conference encompasses multiple types of cancer, and this year many abstracts were submitted about metastatic breast cancer (MBC).  I’ve reviewed the abstracts and taken the liberty of pasting information about those that were not previously in my book, “The Insider’s Guide to Metastatic Breast Cancer.”  To order the book from Amazon or download the complimentary .pdf, you are welcome to visit: https://www.insidersguidembc.com

For hormone receptor positive, HER2 negative patients, a key question has been whether Verzenio (Abemaciclib) can be effective after prior failure on Ibrance or Kisqali.  Based upon the two small studies provided below, the answer appears to be Yes although more robust studies are called for.

Hopefully there’ll be more to come in June after the conference, and I hope you find this helpful!

1. For Hormone Receptor Positive, HER2 Negative MBC
Taking Verzenio after Prior Failure on Ibrance or Kisqali: 
Ibrance, Kisqali and Verzenio are CDK4/6 inhibitors, although Verzenio works somewhat differently.  A small study of 19 evaluable heavily pre-treated HR+ HER2- MBC patients conducted by the Moffitt Cancer Center concluded that Verzenio elicited a response in a significant number of patients who previously took Ibrance in combination with endocrine therapy.  The study participants had previously received a mean of 5.6 prior therapies, and 73.6% had visceral involvement (including brain metastasis in 26%).  15 of the study patients were given Verzenio in combination with endocrine therapy and 4 patients received Verzenio as a single agent.  The median Progression Free Survival (PFS) on Verzenio was 7.0 months, and although no partial or complete responses were observed, 33% of the patients had stable disease. From: https://meetinglibrary.asco.org/record/177494/abstract

From Feb. 2015 to Jan. 2019, a somewhat larger study evaluated clinical outcomes in patients with HR+/HER2- MBC who received Verzenio after progressing on Ibrance or Kisqali.  20 (34%) of the patients on Verzenio had disease progression in less than 3 months, while 21 patients (36%) had a treatment duration exceeding 6 months - including 10 patients who remained on treatment at interim analysis (range 181-413 days).  The median PFS on Verzenio following a prior CDK4/6 inhibitor was 5.8 months.  Interestingly, a preliminary analysis of circulating free DNA revealed RB1 and FGFR1 alterations in patients who exhibited progressive disease.  From: https://meetinglibrary.asco.org/record/175766/abstract

Phase 1 study of Lenvatinib and Letrozole: Lenvatinib, an approved drug that is used to treat liver, thyroid, and kidney cancer, is currently being studied against other types of cancer.  It works by inhibiting vascular endothelial growth factor (VEGF), which is a signal protein produced by cells that stimulates the formation of blood vessels that in turn promote tumor growth.  In a very small study that included 12 MBC patients (8 of whom had prior therapy with a CDK4/6 inhibitor and endocrine therapy), lenvatinib combined with letrozole elicited an overall disease control rate (DCR) of 92% after 12 weeks.  (Anne’s note: Although not explicitly stated in the abstract, it is assumed that all 12 patients had hormone receptor positive disease, although it is unclear whether they were also HER2 negative).  From: https://meetinglibrary.asco.org/record/175824/abstract

Potential Impact of Being on a CDK4/6 Inhibitor before Moving on to Afinitor:  A small study examined the medical records of 33 patients who underwent therapy with Afinitor and Aromasin (A/A).  17 of the patients had prior CDK4/6 inhibitor therapy combined with endocrine therapy and 16 had taken either letrozole or arimidex alone.  In patients who had previously received a CDK4/6 inhibitor, the PFS was 5.7 months vs. 4.7 months in patients who had taken letrozole or arimidex alone.  The median overall survival of patients who’d had a prior CDK4/6 inhibitor was 17.8 months vs. 11.4 months for those who had only taken letrozole or arimidex.  The study concluded that A/A was effective for patients who had previously received CDK4/6 inhibitor therapy and for those who had received prior therapy with an aromatase inhibitor alone.  From: https://meetinglibrary.asco.org/record/177375/abstract

2. For HER2 Positive MBC

Prognostic Factors Relative to HER2 Positive Patients:
A Canadian study evaluated the clinical characteristics of 119 evaluable patients with HER2+ MBC and an unusually prolonged response to anti-HER2 therapy.  The patients had been treated with either: 1) Herceptin, Perjeta, and a taxane 2) Herceptin plus chemotherapy, or 3) TDM-1.  Patients with median duration of response that was 2 times higher than the Phase 2 or 3 trials for each regimen were included in the study due to their prolonged response.  41% of these patients were NED (No Evidence of Disease) and 59% had residual disease.  It was determined that patients who were NED were generally under the age of 50 and had never had breast surgery.  Patients who were NED enjoyed relative longevity when compared with patients who had residual disease.  Treatment type and number of organs with metastases were deemed to be merely of borderline significance. From: https://meetinglibrary.asco.org/record/176119/abstract

Conversely, the Cleveland Clinic evaluated 47 HER2+ patients, many of whom also had hormone receptor positive disease.  17 patients (36%) had a mastectomy after diagnosis of stage IV breast cancer.  The two-year OS (Overall Survival) for the 17 patients who had a mastectomy was 94%, and the two-year OS for the 30 patients with no mastectomy was 50%. The study concluded that on univariable analysis (as a single statistical variable), only mastectomy vs no mastectomy predicted OS, and that on multivariable analysis, mastectomy vs no mastectomy remained a statistically significant predictor of OS.  The study furthermore determined that age, chemotherapy, HER2-directed therapy, and breast radiation were not independent predictors of improved OS.  From: https://meetinglibrary.asco.org/record/177083/abstract

3. General:
Low Dose Metronomic Chemotherapy:
In a retrospective case-control-analysis, the effectiveness of low dose metronomic chemotherapy (LDMC) was compared with conventionally-administered chemotherapy in 105 MBC patients taking cytoxan and methotrexate.  Of the 35 patients taking LDMC, 31% had a disease control rate (DCR) at 6 months vs. 26% of the 70 patients taking conventional chemotherapy.  In the TNBC MBC group, 30% of the LDMC patients showed a DCR vs. 5% of the patients in the control group.  From: https://meetinglibrary.asco.org/record/171918/abstract

Chicagoan

Good to know that Versenio might be an option after Ibrance. Thanks!

ABeautifulSunset

Thanks for keeping us updated, Anne.