Should Medicare Part B Drugs Get Budget Cap?

MedPAC commissioners discuss ways to lower prices in the program

March 08, 2019

Should there be a cap on Medicare's Part B drug budget? That was one of the options that members of the Medicare Payment Assessment Commission (MedPAC) mentioned here Thursday in a discussion of pricing alternatives.

The binding arbitration model (known as "baseball arbitration") could be used for products with limited competition that exceed a specified cost threshold...

...this model also has the advantage of potentially lowering prices for beneficiaries and taxpayers, although some people may raise concerns about access to drugs if manufacturers decide not to participate in arbitration, which would mean Medicare couldn't cover the drug.

"there is some real danger in treating similar drugs for payment purposes as equivalent for effectiveness and side effects, so I want to be clear there's an ability to provide appropriate treatment,"

The commission did not take any vote on the drug pricing proposals; commission staff will continue working on the issue and it may appear in MedPAC's June report, a spokesman said.

https://www.medpagetoday.com/publichealthpolicy/me...

Vaccine Prolongs Remission in Triple-Negative Breast Cancer

Effect in hard-to-treat subgroup "clinically meaningful"

Treatment with a novel peptide vaccine appeared to delay disease recurrence in triple-negative breast cancer (TNBC) patients with low HER2 expression, a subgroup analysis of a phase II trial found.

At a median follow-up of 26.1 months, disease recurrence occurred in 7.5% of TNBC patients who received nelipepimut-S (NeuVax) compared with 26.7% in the control arm

In the NeuVax and control arms, respectively, rates of disease-free survival (DFS) among the 97 TNBC patients were:

• 92.6% versus 70.2% at 24 months

• 82.3% versus 70.2% at 36 months

Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy

Published: 06 February 2019 (correction published 20 Feb 2019)

Abstract: Elevated MYC expression sensitizes tumor cells to apoptosis but the therapeutic potential of this mechanism remains unclear. We find, in a model of MYC-driven breast cancer, that pharmacological activation of AMPK strongly synergizes with BCL-2/BCL-XL inhibitors to activate apoptosis. We demonstrate the translational potential of an AMPK and BCL-2/BCL-XL co-targeting strategy in ex vivo and in vivo models of MYC-high breast cancer. Metformin combined with navitoclax or venetoclax efficiently inhibited tumor growth, conferred survival benefits and induced tumor infiltration by immune cells. However, withdrawal of the drugs allowed tumor re-growth with presentation of PD-1+/CD8+ T cell infiltrates, suggesting immune escape. A two-step treatment regimen, beginning with neoadjuvant metformin+venetoclax to induce apoptosis and followed by adjuvant metformin+venetoclax+anti-PD-1 treatment to overcome immune escape, led to durable antitumor responses even after drug withdrawal. We demonstrate that pharmacological reactivation of MYC-dependent apoptosis is a powerful antitumor strategy involving both tumor cell depletion and immunosurveillance.

https://www.nature.com/articles/s41467-019-08541-2

Nature Communicationsvolume 10, Article number: 620 (2019)

(Cannot locate a DOI. Sorry)

Thanks for providing a prompt to this article Minniesi.

Adjuvant Chemotherapy for ER+ Breast Cancer -

A Sea Change Is Underway

Adjuvant breast cancer treatments—chemotherapy, human epidermal growth factor receptor 2 (HER2)–targeted therapies, and endocrine therapy—prevent recurrence and extend survival. Unfortunately, because risk assessment is imprecise and treatments are not uniformly effective, many women are treated to benefit a small number. Chemotherapy has the most onerous short-term side effects and is the treatment that patients most wish to avoid.

Over the past 15 years, multiple genomic assays have been developed that more precisely characterize the risk of developing recurrent breast cancer.

...use of adjuvant chemotherapy for patients with stage I–II ER+/HER2- disease declined from 26.6% to 14.1% and 81.1% to 64.2% among node-negative and node-positive patients, respectively, between 2013 and 2015.

With the advent of targeted therapy for breast cancer, both oncologists and their patients appear less willing than in the past to take a toxic treatment for a very small benefit.

...a National Comprehensive Care Network database study demonstrated excellent outcomes for patients with small ER+/HER2- tumors not treated with chemotherapy with distant recurrence-free survival rates of 98% (T1a) and 96% (T1b). These data suggest that most patients with small ER+ tumors should not receive chemotherapy and may have also led to a decline in chemotherapy use.

Genomic expression assays may ultimately have an even greater impact on the management of young women with ER+ breast cancer, a population that faces the long-term consequences of treatment toxicities.

Whether we are focusing on traditional chemotherapy or targeted approaches, we must strive to integrate prognostic biomarkers such as pathologic complete response and develop new prognostic and predictive biomarkers. Our goal is to provide the adjuvant treatment that allows each patient to remain cancer free and, at the same time, avoid unnecessary toxicity.

https://www.medscape.com/viewarticle/896998?src=mk...

Philip D. Poorvu; Eric P. Winer

J Natl Cancer Inst. 2018;110(5):443-445. © 2018 Oxford University Press

Unusual mechanism of CDK4/6 inhibitor resistance found, may be reversible

Breast cancer cells can acquire resistance to the relatively new drugs known as CDK4/6 inhibitors by producing higher amounts of CDK6, a cell cycle protein, a new study has found, and those cells can transfer their resistant traits to other cancer cells via molecular carriers called exosomes.

This drug resistance mechanism, identified by researchers at Dana-Farber Cancer Institute, is highly unusual, they said, and laboratory studies suggest it may be reversible. Breast cancer cells that developed resistance to a CDK4/6 inhibitor, palbociclib, became sensitive to the drug again after a "treatment holiday" of several weeks when no palbociclib was administered, they said in an article in Cell Reports.....

Experiments showed that cancer cells' resistance to palbociclib could be reversed by stopping treatment with the drug for seven weeks. The treatment "holiday" was tested in mice as well: palbociclib-resistant tumor material was implanted into animals, who were treated with the drug until resistant tumors were established. The drug was then discontinued for 28 days, and after treatment was started again, the tumors shrank.

The discovery that resistance to a CDK4/6 inhibitor is transmitted to tumor cells via exosomes has a potential benefit for patient management, the scientists said. "We may be able to examine patients' exosomes [by means of a blood test] and see if they are becoming resistant earlier than would be apparent because the cancer progressed on radiographic scans," said Shapiro.

Posted on MARCH 05, 2019

https://www.dana-farber.org/newsroom/news-releases/2019/unusual-mechanism-of-cdk4/6-inhibitor-resistance-found--may-be-reversible/?fbclid=IwAR25N3Ms297BuzjWWzOfCQahjNxZOgrcYATopBHgbI50WsXqKCqhIPTfD1c

Expert Discusses the Role of Liquid Biopsies in Breast Cancer

Published Online:4:16 PM, Mon November 5, 2018

The use of next-generation sequencing (NGS) has the potential to improve the treatment of patients with breast cancer, but there are some challenges that still need to be overcome...

"It's not just a matter of the assay itself," Sparano added. "It's a matter of the assay and the limited number of drugs we have available to treat tumors associated with specific molecular alterations."

In an interview with Targeted Oncology, Joseph A. Sparano, MD, associate director for clinical research, Albert Einstein Cancer Center, Montefiore Medical Center, discussed the potential for liquid biopsy and the ongoing challenge of improving survival for patients with metastatic disease.

https://www.targetedonc.com/news/expert-discusses-the-role-of-liquid-biopsies-in-breast-cancer

{Brief interview discusses liquid biopsies in Q and A format.}

april1964: I hear ya! It's all about quality of life! (But I must say, that article was sobering.)