Dual-Drug Therapy May Boost Odds Against a Tough Breast Cancer

In continuation of my updates on  fulvestrant (Faslodex) and anastrozole (Arimidex)

           

 There's good news for women battling a particularly difficult form of advanced breast cancer.

In a new study of patients with so-called "hormone receptor-positive" breast cancer that's spread beyond the breast, women who received a combo of two anti-estrogen drugs right away lived many months more than those who got just one drug, the researchers found.

The drugs -- fulvestrant (Faslodex) and anastrozole (Arimidex) -- appear to work better when given together rather than using fulvestrant as a follow-up drug given after anastrozole, according to the team led by Dr. Rita Mehta. She's a clinical professor at the University of California, Irvine.

"These results are very exciting," said Mehta, who is also a member of the Southwest Oncology Group breast cancer research committee.

"Women who are treated with fulvestrant up front live about eight months longer. That's a lot of extra time to do the things you love with the people you love," she said in an Oregon Health & Science University news release.

"Women who received fulvestrant, right up front, lived longer based on this new long-term analysis. This is credible evidence that combination endocrine therapy should be considered an option for first-line treatment of advanced hormone receptor-positive breast cancer," Mehta said.

One breast cancer specialist who wasn't involved in the research agreed.

"Although metastatic breast cancer is not thought to be curable, it can be controlled for years and converted to a chronic disease that allows patients to carry on with their lives," explained Dr. Alice Police. She directs breast surgery at Northwell Health Cancer Institute in Sleepy Hollow, N.Y.

That's true for all advanced breast cancers, including the hormone receptor-positive tumors covered by this study. About two-thirds of all breast cancers are of this type, according to the American Cancer Society.

These hormone-sensitive tumors "love estrogen," Police noted, and so oncologists typically prescribe anti-estrogen drugs to help slow the disease.

"Typically, a patient is treated sequentially with different medications [such as fulvestrant and anastrozole], and switched to a different medication if their cancer spreads or grows," she explained.

But what if women got the two drugs in combination, right away?

To answer that question, Mehta's group tracked outcomes for over 700 postmenopausal women with breast cancer treated at 73 hospitals, clinics and cancer centers across the United States and Canada.

The investigators found that women who received both medicines as their first line of treatment lived an average of eight months longer than those who took anastrozole alone -- 50 months versus 42 months.

The study findings also showed that 42 percent of women who got the combo treatment were alive five years after their treatment, compared with 33 percent of women who got anastrozole alone.

About 45 percent of women treated with anastrozole alone were later treated with fulvestrant, when their cancer got worse or spread. But those who initially received fulvestrant had the best overall survival and progression-free survival, the researchers reported March 27 in the New England Journal of Medicine.

The study also found that patients in the combo-treatment group received lower-than-normal doses of fulvestrant in the trial: 250 milligrams (mg) per month after the first loading dose, compared with the typical 500 mg per month.

The two drugs work in slightly different ways. Anastrozole reduces the body's production of estrogen, while fulvestrant disables the tumor's ability to "feed" on circulating estrogen.

https://en.wikipedia.org/wiki/Fulvestrant

https://en.wikipedia.org/wiki/Anastrozole

Dual-Drug Therapy May Boost Odds Against a Tough Breast Cancer 

Pomegranates May Prevent Growth of Breast cancer cells.....

We know that Pomegranate aril juice provides about 16% of an adult's daily vitamin C requirement per 100 ml serving, and is a good source of vitamin B₅ (pantothenic acid), potassium and antioxidant polyphenols.  The most abundant polyphenols in pomegranate juice are the hydrolyzable tannins called punicalagins which have free-radical scavenging properties in laboratory experiments. Punicalagins are absorbed into the human body and may have dietary value as antioxidants. Other phytochemicals include polyphenols catechins, gallocatechins, and anthocyanins such as prodelphinidins, delphinidin, cyanidin, and pelargonidin.   Many food and dietary supplement makers have found advantages of using pomegranate phenolic extracts as ingredients in their products instead of the juice. One of these extracts is ellagic acid which may become bioavailable only after parent molecule punicalagins are metabolized. However, ingested ellagic acid from pomegranate juice does not accumulate in the blood in significant quantities and is rapidly excreted. Accordingly, ellagic acid from pomegranate juice does not appear to be biologically important in vivo.

Now researchers lead by Dr Shiuan Chen, director of the Division of Tumour Cell Biology, and Dr Lynn Adams, a research fellow at the centre's Beckman Research Institute have found that Pomegranates contain a group of compounds called ellagitannins ( glucosidesof elligacic acid) may prevent the growth of breast cancer cells. Researchers tried to determine whether chemicals in pomegranates could block the action of an enzyme called aromatase. Aromatase plays a key role in driving the growth of some forms of breast cancer by helping the body produce the female sex hormone oestrogen. Breast cancer drugs like anastrozole are designed to block its action.

The researchers screened ten ellagitannin-like compounds and found that one in particular, Urolithin B, (see above structure) significantly inhibited breast cancer cell growth in the laboratory. Its interesting to note that phytochemicals in pomegranates to exhibit this property (earlier the same authors have reported the inhibition of aromatase by grapes (phytochemicals).

Though further studies like in vivo are essential to further substantiate the in vitro studies (relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells) are essential (because of the fact that  the ellagitannins are not well absorbed into blood when provided in the diet), still in my opinion its a good finding......

^{Ref : http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/3/1/108}

Bisphosphonates play a role in reducing recurrent breast cancer....

We know that bisphosphonates (also called diphosphonates) are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases. Bone has constant turnover, and is kept in balance (homeostasis) by osteoblasts creating bone and osteoclasts digesting bone. Bisphosphonates inhibit the digestion of bone by osteoclasts. Osteoclasts also have constant turnover and normally destroy themselves by a process called cell suicide (apoptosis). Bisphosphonates encourage osteoclasts to undergo apoptosis. Though other uses like in he treatments of osteoporosis, osteitis deformans, bone metastasis, primary multiple myeloma,hyperparathyroidism and osteogenesis imperfecta were known. A new data suggests that these agents may play a role in reducing recurrent breast cancer as well. Zoledronic acid (see the structure) is both safe and effective in preventing bone loss in postmenopausal women with breast cancer who are treated with aromatase inhibitors, according to data presented at the CTRC-AACR San Antonio Breast Cancer Symposium. Women who take aromatase inhibitors need some sort of bone protection, and this five-year data show that zoledronic acid is a viable option.

As per the claim by the researchers lead by Dr. Adam Brufsky , women who are on Medicare tend to go with tamoxifen because the cost of anastrozole puts them squarely in the donut hole of Medicare Part D, but once the cost barrier is removed there will likely be a mass switch to the aromatase inhibitor, which will necessitate the need for bone protection. More interestingly, in the same conference a research group lead by Rowan Chlebowski presented a study wherein "women who used bisphosphonates, had significantly fewer invasive breast cancers than women who did not use bisphosphonates. .......

http://www.upci.upmc.edu/news/upci_news/121009_study.cfm

FDA Approves Orserdu (elacestrant) for Patients with ESR1 Mutations in ER+, HER2- Advanced or Metastatic Breast Cancer

The Menarini Group (“Menarini”), a leading Italian pharmaceutical and diagnostics company, announced  the U.S. Food and Drug Administration (FDA)   approval of  Orserdu for the treatment of postmenopausal women or adult men, with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline Therapeutics (“Stemline”), a wholly-owned subsidiary of the Menarini Group, headquartered in New York and focused on bringing transformational oncology treatments for cancer patients, will commercialize Orserdu in the U.S.

“The FDA approval of Orserdu marks the first ever therapy for ER+, HER2- advanced or metastatic breast cancer patients with ESR1 mutations and we are very proud to offer a targeted therapy addressing this huge unmet need,” commented Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. “We are grateful to the patients, investigators and administrators who participated in the clinical trials that led to this remarkable innovation.”

Orserdu is approved under the FDA’s Priority Review and Fast Track designation based on the results of the registrational Phase III trial EMERALD, that demonstrated statistically significant progression-free survival (PFS) with elacestrant vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane), meeting both primary endpoints in all patients and in those patients whose tumors harbor ESR1 mutations.

In the group of patients whose tumors had ESR1 mutations, elacestrant reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC. A post-hoc analysis of the PFS results based on the duration of prior CDK4/6i inhibitors (CDK4/6i) usage was presented at San Antonio Breast Cancer Symposium (SABCS) in December 2022. The median PFS was 8.6 months on elacestrant vs 1.9 months for SOC, in those patients whose tumors harbored ESR1 mutations and had been treated with a CDK4/6i for at least 12 months.

Safety data is consistent with the other endocrine therapies. Most of the adverse events (AEs), including nausea and musculoskeletal pain were grade 1 and 2. No hematological safety signal was observed and none of the patients in either of the two treatment arms had sinus bradycardia.

“Advanced or metastatic ER+, HER2- breast cancer pre-treated with endocrine-based therapy remains an area of unmet medical need. The last endocrine therapy approved was about 20 years ago, and effective endocrine options for this patient population are needed,” said Dr. Aditya Bardia, MD, MPH, Director of Breast Cancer Research at Mass General Cancer Center, Associate Professor at the Medicine Department at Harvard Medical School, and Principal Investigator for the EMERALD trial. “ESR1 mutations are a known driver of resistance to standard endocrine therapy, and so far, have been difficult to treat. The approval of elacestrant is welcomed as it offers a novel option for patients with ER+, HER2- metastatic breast cancer. This therapy targets the ESR1 mutations in metastatic breast cancer and provides patients with a convenient oral once-daily dose.”

“Each year 300,000 Americans are diagnosed with breast cancer and metastatic breast cancer causes the vast majority of deaths from the disease: more than 43,000 annually. We urgently need new and better treatment options to extend and improve the lives of people with metastatic breast cancer,” said Sonya Negley, Executive Director, Metavivor. “We are thrilled to see the approval of Orserdu, a new oral endocrine therapy, for patients who have tumors that harbor ESR1 mutations, which are present in up to 40% of ER+, HER2- advanced or metastatic breast cancer. We advise patients to get tested for ESR1 mutations at progression in their metastatic treatment, so that their healthcare team can identify the right treatment options for their disease.“

Read More ...

https://en.wikipedia.org/wiki/Elacestrant

FDA Approves Orserdu (elacestrant) for Patients with ESR1 Mutations in ER+, HER2- Advanced or Metastatic Breast Cancer