Afinitor/Aromasin

Longtermsurvivor · December 2015

It's nearly 2016, but this still appears to be the active Afinitor thread at bc.org

Here's an interesting and related news story about its effectiveness, unwanted effects and FDA approval:

http://m.jsonline.com/watchdog/watchdogreports/fda-repeatedly-approved-cancer-drug-afinitor-without-proof-it-extended-life-b99628814z1-361607291.html

Healing blessings for all, Stephanie

3-16-2011 · December 2015

wow, longtermsurvivor Thanks for the article.

Mary

bestbird · December 2015

Stephanie, thank you for the link to the Afinitor article. The article states that the drug may elicit formidable side effects and consequences, as follows:

In the trial for advanced breast cancer, 63% of those taking Afinitor had to cut the dose of the drug or temporarily stop treatment. and nearly one in five developed a potentially fatal lung condition known as noninfectious pneumonitis... Since 2009, the year the drug first got on the market, there have been nearly 9,000 reports of serious adverse reactions among Afinitor users, including more than 2,700 deaths and more than 3,100 hospitalizations.

(Certainly nothing to be taken lightly!)

RosesToeses · December 2015

I hope you all don't mind me butting back in here even though I'm no longer on Afinitor. I read the article and it brings up good information about the potential side effects of Afinitor, but I sort of resented what seemed to me like a very sensationalistic tone.

It's true that Afinitor has some bad potential side effects, but I think it's on the oncologist to discuss those and weigh them with patients, not for the FDA to deny approval for a drug that more than doubles PFS. It would be one thing if the side effects were covered up and people were being prescribed Afinitor before easier drugs without knowing, but I don't see that being the case here. I think most of us have already failed AIs, Faslodex, and, now that it's on the market, Ibrance, too. In this situation, it seems like the question is whether Afinitor is harder to take than chemo or whatever the other options on the table are, not whether it's harder to take than not having cancer.

I'm not railing at you, Stephanie, I'm just frustrated that the article's authors seem to me to be so clueless about what having stage IV cancer is all about and what's really at stake here.

Ok, rant over! :-D

Longtermsurvivor · December 2015

HI Anne,

Thanks for your perspective on the article.

I also posted it at

https://www.bcmets.org/archive/2015/12/date

And

https://www.smartpatients.com/conversations/16992

(free registration required)

At the former, there were cautionary tales about bad experiences with Afinitor. At the latter site, there was still much enthusiasm for it, especially among those dealing with kidney cancer who often have advanced disease and very few viable treatment options. From my years of thinking about mTOR inhibitors (it's linked to my rare, genetic disorder), I appreciate that this is a "best" option for some and a "last ditch" or detrimental option for others.

Hi RosesToes,

I didn't take your statements personally at all! Similar situations in breast cancer treatment are Avastin and high dose chemotherapy with stem cell transplant. They were both treatments that started out the gate with great promise, but the adverse effects and lack of positive effects, including improvement in overall survival, led to their becoming less favored treatments...once accurate efficacy and safety data filtered in.

Thanks everyone for welcoming me here. I've been listening as a silent member for years, but have protected my energy by not getting involved in another online cancer group. Now I really need to meet others dealing with ascites, cachexia and talking about dying and death.

So grateful, Stephanie

starbrightlyshines · December 2015

My tumor markers aren't cooperating. They are slightly rising which means (for me) that A/A isn't really working. Maybe enough to kind of keep the cancer in check, but not the result I was hoping for. My onc wants me to stay on it for another month and see how my markers are then and possibly do another PET. I had one done in Nov, there were somethings the radiologist said were false "positive" because they didn't show up on the regular CT. I just feel like something is brewing and it makes me nervous. My onc acknowledges how hard it is to be in this in between area........and some days I do Ok with it. Today was not one of those days. I am feeling overwhelmed with the holidays, and not coping well with the everyday life of having a family. They are my biggest joy. They are what gets me out of bed in the morning. I am so grateful for them but I feel like I am letting everyone down and I am a huge financial drain on my family. Tomorrow will be better, but today hasn't been easy.

3-16-2011 · December 2015

Hi to everyone new and old to this treatment and those who maybe havent had it yet.

I appreciate the article and like to stay informed from multiple sources. I am glad it shares information I heard from my MO. When presented with choice of how to respond to recent progression, MO did remind me that the long term plan is to try everything. Afinitor has not. been too bad so far. But I do have new bone pain. (tumor markers dont. mean anything for me). Pain is not disabling so will wait for scan in Feb. unless pain gets worse.

Star, so sorry for your low day. I do love/hate the holidays as I can become overwhelmed. I wish for you a good day tomorrow.

Sue2009 · December 2015

hello, Star brightly shines, I share your sentiments. I started A/A 3 weeks ago on lowest dose. 2.5mg. After 1 week I had dry cough, after 2 weeks I was extremely tired, cough became productive. Dr wanted to admit me, but I refused, so affinitor stopped for now & started Zithromax. I also have had a hoarse voice for week now. I have read bad press on affinitor. 2 & half yrs ago MDA offered this combo, my MO back in Fl recommended against it, said my QOL would go down, & it would not prolong my life. New MO says she has seen good results w/A/A. My counts after 2 weeks went down significantly. It may be the holidays have me down too, but I just don't have good feeling about my present treatment.

brandall · January 2016

I've been on AA for 8 months and will have a PET scan on Monday. If everything is okay, I will start my 9th cycle then. I started on 10mg and had to dose reduce to 7.5mg (after a 2 week break) because my liver levels were rising rapidly. I just had blood work done last week and my liver levels were rising rapidly again so dose reduction to 5mg. I also have grade 1 pneumonitis (I never had a cough, a shady spot showed up on a scan), which is a bit frightening, but I am being closely watched by a pulmonologist as well as my oncologist. The pneumonitis did respond to steroids, so that is good news. They have all agreed that I can stay on the AA as right now the benefits are outweighing the risks. I find this drug to be really strange. At the beginning I had mouth sores, high blood pressure and a rash that was awful and would not go away for months. After being on blood pressure drugs for 2 months I was able to wean off them. The mouth sores just pop up randomly with no rhyme or reason. The rash went away after about 4 months. Now 8 almost 9 months in the mouth sores are back and so is the rash, ugh. The hardest hit has been my liver. My liver enzymes are over twice the high level of normal…and again the pneumonitis. So, I am hoping the PET still shows stable, but also wondering if my body needs a break from AA. Ironically the worst side effects I don't feel, I actually feel quite good!

Kiss77 · February 2016

Hi all,

I started AA month ago. My markers are up, a lot, and there is slight progression in the liver (seen on ultrasound). Do you think a month is enough for AA to work? Meeting with onc is next week.I have failed 4 lines of treatment for the past year and a half and right now I want this one to work with all my heart.

3-16-2011 · February 2016

Kiss77,

The only reassurance I can give is my MO waited 4 months to scan me after starting A/A stating "we have to give it time to work". I had increased bone pain after 2 months but we waited. My scan last week showed stable Smile . My tumor markets are meaningless, so scans are all I have to check progression.

I wish you peace

Mary

Kiss77 · February 2016

Mary, thank you, thank you, thank you! And congratulations for stable scan!

sueper13 · February 2016

Hi, all. New to the thread but not the disease. Stage IV since 2011, diagnosed with liver mets summer 2015. Gemzar/ carboplatin failed, cyber knife treated 5 cm tumor in liver we think, one month post cyber knife MRI showed three new liver mets. Trying afinitor/aromasin even though recent biopsies show er negative now. (Was strongly positive). Taking 10 mg day for three weeks now, I started out at 10 mg. day. Trying this for eight weeks and then new scans. Had dry lips/ mouth/ throat about two weeks in, managed with lip balm and lots of water

I have the rash. I've had it for about a week and it does migrate. Taking Benadryl and lots of baths followed by plain moisturizing. Spoke with onc nurse this afternoon and she says keep doing what I'm doing and call her back Wednesday or Thursday and let her know if it is better or if it is worse. I hate rashes.

3-16-2011 · February 2016

Hi Sueper

I had a rash after taking A/A . It was uncomfortable. I was instucted to do the same things that you are doing with two exceptions. I took claritin not benadryl, and MO gave me steriod cream for places that rash was the worst. I wish you quick healing.

Mary

sueper13 · February 2016

Thanks, Mary

Sue2009 · February 2016

I started AA in Dec @ 2.5 mg. stopped it from Christmas until after new yrs. After low ANC, chronic sore throat & fatigue I am finally going to take 5 mg every other day, 2.5mg other day. No rash, but skull pain is up & down. Next scan in April. My blood sugars have started to go up & I feel like I have to stay away from sweets.

Longtermsurvivor · April 2016

Bump for Lyndal

Longtermsurvivor · May 2016

Report from small study of 35 patients in Japan -

Efficacy and safety of everolimus for heavily pretreated patients with ER+/HER2- metastatic breast cancer.

http://abstracts.asco.org/176/AbstView_176_168737....

Sub-category:

ER+

Category:
Breast Cancer—HER2/ER

Meeting:
2016 ASCO Annual Meeting

Abstract No:
e12041

Citation:
J Clin Oncol 34, 2016 (suppl; abstr e12041)

Author(s): Tomofumi Osako, Reiki Nishimura, Yasuyuki Nishiyama, Mamiko Fujisue, Mitsuhiro Yamada, Kyoko Suko, Junko Morioka; Breast Center, Shinto General Hospital, Kumamoto, Japan; Breast Center, Kumamoto Shinto General Hospital, Kumamoto City, Japan; Breast Center, Kumamoto Shinto General Hospital, Kumamoto, Japan; Kumamoto Shinto General Hospital, Kumamoto, Japan; Department of Pharmacy, Shinto Genreal Hospital, Kumamoto, Japan; Department of Pharmacy, Shinoto General Hospital, Kumamoto, Japan

Abstract Disclosures

Abstract:

Background: Everolimus is effective for patients with ER+/HER2- metastatic breast cancer. In BORELO 2 trial, about the half of the patients were treated previously with less than two therapies and the sensitivity to the previous endocrine therapy was more than 80%. However, efficacy and safety of everolimus for heavily pretreated patients with metastatic breast cancer are unknown.

Methods: From April 2014 to January 2016, 35 patients with ER+/ HER2- metastatic breast cancer were treated with everolimus in our hospital. Most patients received more than 3 endocrine therapies after recurrence. We examined their clinical backgrounds and outcomes.

Results: The median follow-up time was 11.1 months. Forty-eight percent of patients had metastases in one organ, 28% in 2 organs and 24% in more than 3 organs. Twenty-four percent of patients had lung metastasis, 38% had liver metastasis and 42% had bone metastasis. Eighty percent of patients received more than 3 endocrine therapies after recurrence. Responses for more than 6 months to the previous endocrine therapies were confirmed in 32% of patients. Fifty-five percent of patients were treated with chemotherapy after recurrence.

Complete response was obtained in 0% patient, partial response in 10%, stable disease in 59% and progressive disease in 14%. The median progression-free survival with everolimus treatment was 114 days. Seventy-two percent of patients had stomatitis (G3 18%), 17% had pneumonitis (G3 3%) and 21% had dermatitis.

The reasons of discontinuation of everolimus treatment were disease progression in 61% patients, pneumonitis in 17%, stomatitis in 17% and others in 4%. Thirty-four percent of patients continued treatment with 10mg/day of everolimus until progression. Three out of 4 patients who discontinued everolimus treatment because of stomatitis had taken 10mg/day of everolimus. All the 4 patients who discontinued everolimus treatment because of pneumonitis had taken 10mg/day of everolimus.

Conclusions: There was no significant difference of response rates, however, the progression-free survival with everolimus treatment was shorter than that in BORELO 2 trial. We may control the severe adverse events by reducing the dose of everolimus.

Longtermsurvivor · May 2016

Prevention of everolimus/exemestane (EVE/EXE) stomatitis in postmenopausal (PM) women with hormone receptor-positive (HR+) metastatic breast cancer (MBC) using a dexamethasone-based mouthwash (MW): Results of the SWISH trial.

Sub-category:
ER+

Category:
Breast Cancer—HER2/ER

Meeting:
2016 ASCO Annual Meeting

Abstract No:
525

Poster Board Number:
Poster Session (Board #13)

Citation:
J Clin Oncol 34, 2016 (suppl; abstr 525)

Author(s): Hope S. Rugo, Lasikas Seneviratne, J. Thaddeus Beck, John A. Glaspy, Julio Antonio Peguero, Timothy J. Pluard, Navneet Dhillon, Leon C. Hwang, Chaitali Singh Nangia, Ingrid A. Mayer, Timothy F. Meiller, Mark Steven Chambers, Ghulam Warsi, Robert William Sweetman, J. Randy Sabo, Jennifer Keating Litton; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Los Angeles Cancer Network, Los Angeles, CA; Highlands Oncology Group, Fayetteville, AR; University of California Los Angeles School of Medicine, Los Angeles, CA; Oncology Consultants PA, Department of Research, Houston, TX; St Luke's Cancer Institute, Kansas City, MO; Cancer Treatment Centers of America, Atlanta, GA; Kaiser Permanente Mid-Atlantic States, Gaithersburg, MD; University of California Irvine Health Chao Family Comprehensive Cancer Center, Orange, CA; Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, TN; Oncology and Diagnostic Sciences, Dental School and The Marlene and Stewart Greenebaum Cancer Center University of Maryland Medical Center, Baltimore, MD; The University of Texas MD Anderson Cancer Center, Houston, TX; Novartis Pharmaceuticals Corporation, East Hanover, NJ

Abstract Disclosures

Abstract:

Background: Stomatitis is a significant complication associated with mTOR inhibition. In BOLERO-2 patients (pts) receiving EVE/EXE, all grade (Gr) stomatitis was 67%; 33% had Gr ≥ 2 and 8% Gr 3. The median time to ≥ Gr 2 onset was 15.5 days, the incidence of new stomatitis (Gr ≥ 2) plateaued at 6 wks. In a meta-analysis, 89% of first stomatitis events occurred within 8 wks. Topical steroids are used to treat aphthous ulcers; anecdotal use as prophylaxis has been reported.

Methods: Eligibility included PM women with HR+ MBC prescribed EVE/EXE. Treatment included EVE 10 mg and EXE 25 mg QD, with 10 mL of commercially available 0.5 mg/5 mL dexamethasone oral solution to swish x 2 min, and spit QID for 8 wks, starting day 1. Pts completed a daily adherence log, including an oral pain (range 0-10) and normalcy of diet score. The primary endpoint was to compare the incidence of Gr ≥ 2 stomatitis at 8 wks with BOLERO-2 results. Secondary endpoints included: MW use by average times/day, EVE/EXE dose intensity, incidence of all Gr stomatitis and time to resolution to Gr ≤ 1.

Results: 92 women were enrolled; 86 are evaluable for efficacy. Median age was 61 yrs (range 34-87); 38% were treated with EVE/EXEin the ≥ 2nd-line setting. Median dose intensity was 10 (range 3-14) and 25 mg (range 8-25) for EVE and EXE. 95% of pts used the MW 3-4 times/day (median MW use/d = 3.95, range 1.9-4). The rate of ≥ Gr 2 stomatitis at 8 weeks was 2.4% (2 pts) with a Gr 1 rate of 17.4%; there were no ≥ Gr 3 events. A comparison of stomatitis incidence by grade between BOLERO-2 and SWISH is shown in the Table. Mean pain scale score was < 1 at all visits; 86% of pts reported a normal diet at 8 wks. 12% discontinued EVE/EXE due to suspected related adverse events (most common: rash [2%], hyperglycemia [2%], stomatitis [1%] and pneumonitis [1%]).

Conclusions: Prophylactic use of 0.5 mg/5 mL dexamethasone oral solution markedly decreases the incidence and severity of stomatitis in patients receiving EVE/EXE for MBC and should be considered a new standard of care in this setting. Clinical trial information: NCT02069093

Table is here

http://abstracts.asco.org/176/AbstView_176_162147....

Longtermsurvivor · May 2016

Another ASCO abstract, this one on variable dosing with Afinitor/everolimus

Progression free survival and toxicity with dose variations of everolimus in metastatic hormone receptor positive breast cancer.

Sub-category:
ER+

Category:
Breast Cancer—HER2/ER

Meeting:
2016 ASCO Annual Meeting

Abstract No:
e12058

Citation:
J Clin Oncol 34, 2016 (suppl; abstr e12058)

Author(s): Melanie Anne Sheen, Susmitha Apuri, Roohi Ismail-Khan; University of South Florida/H.Lee Moffitt Cancer Center and Research Institute, Tampa, FL; University of South Florida/H.Lee Moffitt Cancer Center and Research Institute, Land O Lakes, FL; H. Lee Moffitt Cancer Center and Research Institute, Department of Women's Oncology, Tampa, FL

Abstract Disclosures

Abstract:

Background: Everolimus is a sirolimus derivative that inhibits the mTOR (mammalian target of rapamycin) pathway. The BOLERO-2 trial showed improved progression free survival (PFS) with combined everolimus and exemestane versus exemestane alone in metastatic hormone receptor positive post-menopausal breast cancer patients. The initial dose of everolimus was 10mg and allowed for two dose reductions, 5mg daily and 5mg every other day. No data is available on PFS or toxicity for patients who were started, or dose reduced and maintained, on lower doses. We undertook a retrospective evaluation of PFS in patients with dose variations to determine if dose reductions adversely affect survival.

Methods: Patients who were treated with the combination of everolimus and exemestane at Moffitt Cancer Center from April 26, 2012 - May 31, 2015 were obtained from our pharmacy database. A total of 138 patients met criteria consistent with BOLERO-2 patients. Chart review was performed to obtain data points.

Results: PFS for the cohort as a total was 7.2 months. 77 patients were started on 10mg daily, 29 patients were started on 7.5mg daily, and 31 patients were started on 5mg daily. Dose reduction occurred in 47% of patients started on 10mg and 41% of patients started on 7.5mg. 22.5% of all patients discontinued treatment for toxicity, 75% of whom started on doses > 5mg. PFS comparison of starting 10mg to the average alternate dose (6.23 mg) was Hazard Ratio (HR) 1.15 (95% CI: 0.77-1.72) p = 0.49. PFS comparison of starting 10mg vs 7.5mg was HR 1.08 (95% CI: 0.65-1.80),p = 0.76 and starting 10mg vs. 5mg was HR 1.21 (95% CI: 0.76-1.95) p = 0.43.

Conclusions: There was no significant difference in PFS between starting the recommended dose or a lower dose. Patients initiated on lower doses were less likely to require dose reductions or discontinue due to toxicity even with later dose increases. This data suggests that progression may not be limited by initiating lower, less toxic doses of everolimus. Therefore, if oncologists are more comfortable starting a lower dose, survival may not be adversely affected and patients may be more compliant, deriving a prolonged benefit from the combination.

Longtermsurvivor · June 2016

Bumping for Artist!

All love ~ Stephanie

Longtermsurvivor · July 2016

All articles mentioned are available free full text. A little hard to understand, but may be good to print and take to your doctor for discussion.

Review medical article on everolimus/afinitor plus exemestane/aromasin:

Open Access

Updates in the Use of the mTOR Inhibitor Everolimus in Advanced Breast Cancer

Jennifer Anderson* and Sandra Cuellar

April 2016

http://www.omicsonline.org/open-access/updates-in-...

Afinitor/Aromasin

Comments

Report from small study of 35 patients in Japan -

Efficacy and safety of everolimus for heavily pretreated patients with ER+/HER2- metastatic breast cancer.

Prevention of everolimus/exemestane (EVE/EXE) stomatitis in postmenopausal (PM) women with hormone receptor-positive (HR+) metastatic breast cancer (MBC) using a dexamethasone-based mouthwash (MW): Results of the SWISH trial.

Progression free survival and toxicity with dose variations of everolimus in metastatic hormone receptor positive breast cancer.

Open Access

Updates in the Use of the mTOR Inhibitor Everolimus in Advanced Breast Cancer

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