Re: Whack-a-mole next...
 

My apologies for not responding sooner, it’s very difficult to find the words. I’ve been given an average lifespan of 6 mos. and I’m just trying to deal the best I can. Feel free to friend me on Facebook or follow me on Instagram: fpk_etc

Re: Whack-a-mole next...
 

Flori,
I am so sorry to hear this news and remember that these prognoses don't necessarily tell the whole of your story. Wishing you peace and strength...... Pam

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You are in no way average! I am sending you strength, love and hugs.

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Flori,

I can only imagine how difficult things are for you presently. Lots to wade through and sort out. I think your story may have more chapters than it appears on the surface. You know that old adage: What's the difference between God and a doctor? God KNOWS he isn't a doctor!!!

I am on Facebook, barely, but will try to reach out. Instagram is beyond my techno-abilities! I know, pathetic old lady here!

It is good to hear from you here, though, tough as it for you to share. We laugh and cry together on this board; pray, rejoice and mourn together. Our hells and our heavens are what bind us, not our wins or losses, and certainly not this beast. We are a group of fighters and we fight as a band of warriors. We are Team Druther, Team Her2Support! We are Team Flori and we've got your back! We want to walk with you wherever it leads, if you will let us, because we love you.

Laurel

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Flori, I am so sorry to hear this. But doctors are wrong all the time. As they say, doctors are only practicing. And also, you know what they call the medical student to finishes last in their class? Doctor! So, there's always hope and hopefully the treatments you've been getting have been kicking the disease in its backside. As I said before, we understand that you have more pressing things going on right now and updating us here isn't your main concern but we do care and we hope you'll let us know what you can when you're up to it. As Laurel said, we've got your back and we're here for you. Hugs

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I do not believe doctors when they give timelines. You are a strong warrior and I know you can defy the odds! All my love and prayers for you Flori - prove them wrong!

God Bless,

Jessica

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Dear Flori,

I'm with Jessica re: doctors and their timelines. Many of us would be speaking from the grave if their timelines were valid.

Thinking of you and sending positive thoughts

xoxo
janis

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Flori Flori morning glory, I agree about Dr's time lines and think we're connected on FB. The world has changed so much since Joe and Christine started this site and I'm sure treatments have too. Keep fighting and know your friends here are with you in spirit.

Re: Whack-a-mole next...new target for "Lazarus effect"--keep up the hope
 

HEALTH NEWSSEPTEMBER 6, 2019 / 7:58 AM / UPDATED 4 HOURS AGO
Inside drugmakers' strategy to boost cancer medicines with 'Lazarus effect'
Julie Steenhuysen, Ludwig Burger
8 MIN READ
(Reuters) - In the halls of MD Anderson Cancer Center, the drug Vitrakvi is known for having a “Lazarus effect” in some patients because it can reverse late-stage cancer that has defied all other treatment options.


Developed by Eli Lilly and Co’s (LLY.N) Loxo Oncology and marketed by German drugmaker Bayer (BAYGn.DE), it fights a rare genetic mutation that appears in less than 1% of solid tumors, regardless of where they appear in the body.

Finding those patients will require widespread adoption of sophisticated tests that look for multiple genetic alterations that could be driving the cancer.

So far, progress has been slow.

Adoption of so-called next-generation sequencing (NGS) tests has been stalled by lack of reimbursement from insurers over concerns that the evidence is not there yet to support widescale use, according to more than a dozen interviews with oncologists and pharmaceutical and diagnostic industry executives.

As a result, pharma companies from small biotech Blueprint Medicines Corp (BPMC.O) to larger rivals Lilly and Roche Holding AG (ROG.S) are taking matters into their own hands, bulking up staff to increase patient and physician awareness about testing and building up a gene testing infrastructure that for many community hospitals still does not exist.

Bayer executives told Reuters it plans to spend $70 million to increase patient and physician awareness of testing for rare mutations and to encourage regulatory approval of more tests. They expect that budget to expand as Vitrakvi continues to win approval in other countries.

Lilly told Reuters the company has signed an agreement with Thermo Fisher Scientific (TMO.N) to develop a companion diagnostic test for its experimental drug, LOXO-292.




The deal adds RET mutations - the target of both Lilly’s and Blueprint’s drugs - to Thermo’s Oncomine Dx Target Test, which local pathology labs can use to identify multiple genes linked with non-small cell lung cancer.

The agreement is aimed to help identify more lung and thyroid cancer patients who may benefit from the Lilly or Blueprint therapies. The Thermo test is already approved by the U.S. Food and Drug Administration - a key standard for Medicare coverage, the companies said.

According to Dr. Brian Alexander, chief medical officer of Roche’s gene testing company Foundation Medicine, only about 15% of U.S. patients with advanced cancers get comprehensive genomic profiling. Another 25% get single-gene testing, he said, and a large proportion “are not getting any testing at all.”

At MD Anderson, which sees 100,000 new cancer patients a year, only around 10,000 eventually have their tumors sequenced.

For a rare few, the tests are lifesaving.

Xin Zheng, 47, a mother of three in Michigan who was referred to Reuters by Blueprint, was diagnosed with stage 4 lung cancer in 2016. After failing several treatments, she was out of options.

Her husband, Zhigang Wei, asked for genetic sequencing, and the test turned up a RET mutation. After contacting multiple lung cancer experts, Zhigang found an early-stage clinical trial treating patients with Blueprint’s experimental drug, BLU-677.

Now, Xin is nearly back to normal.





“My wife is lucky,” he said, adding her quality of life is much better and she has hope for the future.

Finding patients with such rare mutations is like “looking for the needle in the haystack,” said Stefan Oelrich, head of pharmaceuticals at Bayer.

Dr. David Hyman of Memorial Sloan Kettering Cancer Center, who tested Vitrakvi in clinical trials, said making these tests the norm for advanced cancer patients will require a huge shift in the way oncology is practiced.

“It’s painful to know there are patients out there with these alterations who are dying without knowing about it and without getting any treatments,” he said.

NOT GETTING TESTED

For Bayer’s Vitrakvi and Roche’s Rozlytrek, along with similar drugs in development, genomic testing is critical to finding patients who can benefit from them.

Cancer patients and drug companies alike got a boost last year when the federal Medicare health program for the elderly and disabled said it would cover FDA-approved tests for advanced cancer patients that can identify hundreds of genetic mutations at once. A Medicare endorsement is generally followed by widespread coverage decisions by private insurers.

But the final regulations dropped a requirement that testmakers prove the tests are cost-effective and improve patient care. That created an “evidence gap” that has allowed some insurers, also known as third-party payers, to withhold coverage or demand more proof that they benefit patients, said Jeff Schreier of Diaceutics PLC (DXRX.L), a data analytics company that works with drugmakers to improve diagnostic testing.

“More payers are coming around, but it’s slow,” he said.

FILE PHOTO: Xin Zheng and Zhigang Wei are pictured on a family trip to Crater Lake, Oregon, U.S. in this July 2018 handout photo obtained by Reuters August 30, 2019. Zhigang Wei/Handout via REUTERS
The most recent coverage policy from CVS Health Corp’s (CVS.N) Aetna approves many single-gene tests for specific cancers, but still largely considers multi-gene tests experimental. Anthem Inc’s (ANTM.N) policy limits testing to “medically necessary” use and states there’s “insufficient published evidence” to support widespread testing.

And while Foundation Medicine’s and Thermo Fisher’s tests are getting reimbursed from Medicare, many hospitals such as MD Anderson, which have developed their own tests, are not guaranteed payment. “Reimbursement is still a driving force,” MD Anderson’s Kenna Shaw said of genomic testing, which costs an average of $5,000 per patient globally.

Lilly bought Loxo in January for $8 billion to profit from its targeted drugs in early-stage development. Bayer secured the rights to Loxo’s two leading compounds in a 2017 alliance.

Dr. Anthony Sireci, Loxo’s senior medical director, said the company has been working to “democratize” testing in the United States by increasing its use in local pathology labs, where most cancer testing has traditionally been done. The Thermo Fisher agreement will support those goals and expand patients’ access to “high-quality genomic testing,” he said.

“TEST YOUR CANCER”

Bayer has hired diagnostic experts to help its medical and sales staff assess the barriers to genomic testing and ensure that local pathology labs are including the genetic alterations targeted by its drugs when they profile tumors, the company’s oncology strategic business chief Robert LaCaze said in an interview.

Bayer also launched a public awareness campaign called “Test Your Cancer” that urges patients to ask their doctors about genomic cancer testing. The company is working with testing providers to ensure test reports are easy to understand.

Blueprint, which has six genomically-targeted drugs in development, told Reuters it plans to hire six diagnostics experts to increase awareness of the mutations their drugs target, especially in community medical practices, where 70% of cancers are treated.

Bayer sees signs of progress. Based on internal data, the company estimates average sequencing rates across tumors neared 30% last year, and the company saw a two-fold increase in the number of labs offering tests that carry the mutation targeted by Vitrakvi.

Bayer has not released sales figures for Vitrakvi.

Asked for an update in the most recent earnings call in July, Bayer’s Oelrich said uptake is going “according to plan,” but declined to say how many patients are using the drug. LaCaze said with very rare cancers like the ones Vitrakvi targets, sales growth is “something that will build over time.”

Editing by Michele Gershberg and Edward Tobin

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What a post, Lani! Thank you!

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Sending positive thoughts your ways, dear Flori.
You are one brave warrior woman!


all the best
caya

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Flori,
I usually just just follow quietly and admire you from afar. However, tonight I’ll step up and shout out...I think you are one of the strongest, most wise, and compassionate women I’ve ever come across, in person or electronically. I love you and I’m proud to be on your team.

Re: Whack-a-mole next...
 

Good news on brain/cervical MRI—NOTHING NEW in head and spinal cord met has shrunk way down. Brain met also shrinking — no swelling in cerebellum and nothing to correlate or cause vertigo so with that news me and my dear friends all started to cry. Brain surgeon didn’t yet have report but he came bursting into the room saying “your scans look good” and showed us pics on his iPad. (Of course he did).

I feel like I’m breathing for the first time since this all began. Thinking that I have another three months of life until repeat scans. And remembering 12 years ago when I lived in 3 month bursts.

Thank you for all the support.
Much love and one love.
Flori

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Great news! God is good.

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I'm glad the news was better than expected. Thanks so much for updating us with the information. Keeping you in my thoughts and prayers. Hugs

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Great news Flori, B.H.



all the best
caya

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Yea!!!! Whew! Hard to type through the tears of joy! Man, am I elated! Got your six, Flori-girl! Go live, breathe and dance!!!

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So great to hear!! Dance, dance, dance!

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Best news I have heard today!!! Sending you prayers and best wishes

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Hi Flori,

This is wonderful news. So happy for you and your loved ones.

Jackie

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Thinking about you 3000 miles away! Sending all my love and best best hugs.

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Great news, Flori!

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That's fantastic Flori! Such a roller coaster ride, but I reckon you ride that roller coaster with great attitude and strength.
Best wishes
Marie

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Flori, Flori Morning Glory, We are all so happy for this good news!

Lots of love and support coming your way!

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Lani, your medical and drug reports are the best. I am going to print your recent post about Bayer’s research and their new test. A friend with a serious cancer Dx can maybe take and show her oncologist.

Thank you!

Re: Whack-a-mole next...
 

Vantage Logo May 08, 2019
Astra and Daiichi lay out their plan for a better Herceptin


Jacob Plieth
The companies’ DS-8201 succeeds in breast cancer patients who had failed Kadcyla, and will go before the regulators later this year.

Breast cancer
There was a time, some years ago, when Roche’s Kadcyla was seen by the sellside as the pharma industry’s biggest upcoming launch. The bullish forecasts failed to materialise, but Kadcyla did spawn numerous other Her2-targeting projects seeking to become better versions of Herceptin.

Today one of these, Astrazeneca/Daiichi Sankyo’s DS-8201, succeeded in a phase II breast cancer trial that will serve as the basis for a second-half regulatory filing. More lucrative uses might follow, and the result could vindicate the UK company’s aggressive move to license DS-8201 from Daiichi.

That licensing deal had been roundly criticised both for its up-front element – $1.35bn seemed a huge amount for what was, ultimately, an early-stage project – and the fact that Astra raised equity to help finance it.

But the basis for the tie-up was phase I data that Astra called “unprecedented”, amounting to a 60% remission rate in Her2-positive breast cancer subjects who had failed on an average of seven therapies. The UK company highlighted DS-8201 on last week’s first-quarter financials call.

High-intensity conjugate

Like Kadcyla (trastuzumab emtansine) DS-8201 (trastuzumab deruxtecan) is an antibody-drug conjugate. What makes the Daiichi project unique, its makers argue, is a high-intensity payload and cell membrane permeability, which might enable it to target tumours that express Her2 at relatively low levels.

One line of thinking is that patients retain some degree of Her2 expression even after failing multiple anti-Her2 therapies, and the latest findings, from the Destiny-Breast01 study, suggest that DS-8201’s characteristics translate into a real clinical benefit.

Enrolees had failed two Her2-targeting drugs, Herceptin and Kadcyla, yet a 5.4mg/kg DS-8201 dose showed strong clinical activity in terms of overall remission, the trial’s primary efficacy measure, Astra said today.

Hard data are being held back for a scientific meeting. In addition to efficacy, safety will be closely scrutinised given the expression of Her2 on healthy as well as cancerous cells, the touted efficacy of DS-8201, and the off-tumour toxicity of some potent Her2-directed therapies like CAR-T.

Kadcyla was once thought by the sellside to be capable of bringing in 2020 sales of $4.5bn, but last year’s revenue only just breached $1bn, and the current 2024 forecast is $1.4bn, EvaluatePharma computes.

The main problem is that in Her2-positive breast cancer Kadcyla failed to broaden its approved reach beyond Herceptin-relapsed subjects. In the front-line Marianne study Kadcyla-containing regimens were non-inferior but failed to beat Herceptin.

Analysts at present see DS-8201 selling $1.8bn in 2024, but this will not come from Destiny-Breast01’s third-line use alone. For the drug to make its mark fully it must succeed in the second-line setting head-to-head against Kadcyla, and perhaps also in Her2-low subjects, a brand new use.

Selected trials of DS-8201 in breast cancer
Study Setting Detail Trial ID
DS8201-A-J101 ~8th line, Her2-positive 59.5% ORR NCT02564900
Destiny-Breast01 3rd-line, Her2-positive, post Herceptin & Kadcyla Clinically meaningful ORR NCT03248492
Destiny-Breast02 3rd-line, Her2-positive, phIII confirmatory trial Data in 2020+ NCT03523585
Destiny-Breast03 2nd-line, Her2-positive, post Herceptin, vs Kadcyla Data in 2020+ NCT03529110
Destiny-Breast04 Her2-low, vs physician's choice Data in 2020+ NCT03734029
While there are now several Her2-targeting antibody-drug conjugates in development the evolving situation will also be of great interest to Macrogenics, which is developing a naked anti-Her2 MAb, margetuximab, that has an optimised Fc region.

Margetuximab scored a surprising success in the Sophia trial in subjects who had all failed Herceptin and Roche’s Perjeta, and most of whom had also failed Kadcyla. The success was down to patients who carried the 158F allele, a genetic variant that promotes binding with Fc-optimised MAbs like margetuximab; full Sophia data are one of the big attractions of the upcoming Asco conference.

This subgroup-driven effect might not put margetuximab in direct competition with DS-8201, which Astra might now rely on, along with Tagrisso, to form the cornerstone of its oncology strategy. Given the travails of Imfinzi and tremelimumab in lung cancer the UK group needs all the breaks it can get.

Selected Her2-targeting industry projects
Product Company Pharmacology class
Marketed
Herceptin Roche Anti-Her2 MAb
Perjeta Roche Anti-Her2 MAb
Kadcyla Roche/Immunogen Anti-Her2 MAb-DM1 maytansinoid conjugate
Phase III
DS-8201 Daiichi Sankyo/Astrazeneca Anti-Her2 MAb-cytotoxic drug conjugate
Margetuximab Macrogenics Fc-optimised anti-Her2 MAb
BAT8001 Bio-Thera Solutions Anti-Her2 MAb-maytansinoid conjugate
Phase II
Tucatinib Array/Seattle Genetics Her2-selective TKI
TAS0728 Otsuka Holdings Her2-selective TKI
Phase I
RG6194 Roche Anti-Her2 bispecific MAb
PRS-343 Pieris Pharmaceuticals Anti-Her2 bispecific MAb
ARX788 Ambrx Anti-Her2 MAb-cytotoxic drug conjugate
FS102 F-star Anti-Her2 MAb
PF-06804103 Pfizer Anti-Her2 MAb-cytotoxic drug conjugate
MEN1309 Oxford Biotherapeutics/Menarini Anti-Her2 MAb-maytansinoid conjugate
Source: EvaluatePharma.

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Congratulations Flori. Wonderful news.

God bless,

Cathy

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Yay, wonderful news!!!

Carol

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Hey Flori,

I've been thinking about you and wondering how you were doing. I noticed you've updated your signature to show some stability but also some progression. How are you though? When you're up to us, please give us an update and let us know how you're doing. Hugs

Re: Whack-a-mole next...
 

Checking in again . . . Any updates Flori? Thinking about you.

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Lucy, I was wondering the same thing -----Flori, hope you are doing well.

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Me, too! I have not wanted to be bothersome, but I am thinking of Flori all the time. Hoping you will chime in soon, Flori!

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Flori, Flori Morning Glory?????