ASCO 2017 MBC Recap

Bestbird

The mbc therapy information below was presented at the ASCO (American Society of Clinical Oncology) 2017 conference, and has been extracted from abstracts and medical news because I didn't attend the event in person.

An interesting drug being studied for hormone receptor positive mbc is Abemaciclib, a CDK4/6 inhibitor (the same class of drugs as IBRANCE and Kisqali).I wouldn't be surprised if Abemaciclib, which can be given as a monotherapy (i.e. without an accompanying drug such as Letrozole) is approved this year or in early 2018. Abemaciclib can also pass through the blood brain barrier.

Another treatment of significance is Keytruda, an immunotherapy drug.It has already been FDA-approved for any cancer patient who has metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.From the literature, it may have a broad range of uses among the various subtypes of mbc.

I hope you may find this recap helpful!

Hormone Receptor Positive MBC:

Abemaciclib plus Fulvestrant: Abemaciclib, which is not yet FDA-approved, is a CDK/46 inhibitor (like IBRANCE and Kisquali). Data from the Phase 3 MONARCH 2 trial of HR+/HER2- mbc patients who progressed on prior endocrine therapy and were then treated with abemaciclib and fulvestrant (Faslodex) indicate a 45% decreased risk for progression.

In the trial, patients were randomly assigned in a 2:1 ratio to receive abemaciclib + fulvestrant (446 patients) or placebo with fulvestrant (223 patients).Median progression-free survival (PFS) was 16.4 months for patients on abemaciclib with fulvestrant and 9.3 months for those on placebo with fulvestrant.The median duration of response was not reached for patients on abemaciclib with fulvestrant, and was 25.6 months for those on placebo with fulvestrant.The Objective Response Rate (ORR) was 35.2% for the abemaciclib combination vs 16.1% for patients on fulvestrant alone. (As of June 2017, there are several actively recruiting clinical trials for abemaciclib). From: http://www.cancertherapyadvisor.com/asco-2017/abemaciclib-fulvestrant-breast-cancer-endocrine-effective-treatment/article/666229/

Overall Survival for Patients on IBRANCE Plus Letrozole vs. Letrozole Alone: Despite initial marked differences in Progression Free Survival (PFS) among patients taking IBRANCE plus Letrozole vs. Letrozole alone, subsequent information regarding Overall Survival (OS) showed from the PALOMA-1 Phase 2 trial showed only a modest benefit for patients in the IBRANCE plus Letrozole arm (37.5 months) vs. those taking Letrozole alone (34.5 months). The PALOMA-2 Phase 3 study will provide updated OS figures at a later date. From:http://abstracts.asco.org/199/AbstView_199_193611.html

Potential Impact of Being on Afinitor (Everolimus) before Moving on to IBRANCE:Very little research has been undertaken to determine which specific treatments render a patient less likely to respond to a future treatment.One small study attempted to address this issue in patients who had previously taken Everolimus (Afinitor) and then went on a regimen with the CDK4/6 inhibitor Ibrance (Palbociclib).In the small population in the study (23 patients), the median Progression Free Survival (PFS) was 2.9 months for patients who had previously taken Afinitor and then moved on to an Ibrance regimen, versus 9.5 months for patients on Ibrance who had not previously been on Afinitor;the clinical benefit rates were 17.4% vs. 66.5% respectively.Since this was a small study, more efforts are needed to determine whether the use of Afinitor before IBRANCE (or other CDK4/6 inhibitors) is definitively associated with a low response & clinical benefit rate.From:http://abstracts.asco.org/199/AbstView_199_183542.html

RAD1901 (Elacestrant) Study: RAD1901 is an oral selective estrogen receptor degrader (SERD) which is being evaluated for potential use as an oral non-steroidal treatment for estrogen receptor positive breast cancer at high doses.In a study of 40 heavily pre-treated ER+, HER2-negative advanced breast cancer patients taking RAD1901, the objective response rate (ORR) was 23%, the median Progression Free Survival (PFS) was 4.5 months, and clinical benefit rate at 24 weeks was 42%.Notably, 38% of these patients previously received Faslodex (which is another SERD), 40% received Ibrance (palbociclib) or another CDK inhibitor, and 50% had an ESR1 mutation which may be indicative of hormone therapy resistance.It should be noted that 15 of the 40 patients remained on treatment as of the cut-off date.From: https://www.zacks.com/stock/news/263042/radius-rdus-announces-positive-data-on-breast-cancer-drug

HER2 Positive MBC:

Second-line therapy (AFTER Herceptin, Perjeta, and a Taxane) should be Kadcyla (TDM-1). Kadcyla can confer an Overall Survival (OS) of 29.9 months when used as a second-line therapy, which is superior to Lapatinib (Tykerb) plus Xeloda (Capecitabine) which provided an OS of 25.9 months. (Kadcyla can also be a viable first-line therapy in patients for whom Herceptin, Perjeta and a taxane might be too toxic).From: http://am.asco.org/meeting-on-demand/presentation/breast-cancer-metastatic

Neratinib and Xeloda (Capecitabine) Study for HER2+ MBC Patients with Brain Metastases:Neratinib is an orally-ingested drug that crosses the blood brain barrier (BBB).In a clinical trial of 39 HER2+ pre-treated mbc patients with brain metastasis, the combination of Neratinib and Xeloda patients and expected to reach a total of 60, all patients received once-daily, oral Neratinib who had not received prior therapy with Tykerb, 49% of the patients exhibited an objective response.Of the 39 patients in the study, 30% had undergone surgery, 65% had received prior whole brain radiotherapy (WBR), and 35% had undergone stereotactic radiosurgery to the brain.In the study, patients had a median time to CNS progression of 5.5 months, and median overall survival was 13.5 months, but survival data are still immature, the researchers said.The combo therapy was well-tolerated, with the most common treatment-related adverse event being treatable diarrhea. From: https://breastcancer-news.com/2017/06/08/pb272-capecitabine-shows-promise-for-breast-cancer-brain-metastasis/

TNBC MBC:

Keytruda (Pembrolizumab): Keytruda has already been FDA-approved for any cancer patient who has metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.Based upon recent research,-Keytruda has been found to be effective in mbc patients with TNBC, according to an international clinical trial led by NYU.The trial investigated Keytruda in two separate cohorts (groups) of patients: Cohort A, which included 170 heavily pre-treated mbc TNBC patients regardless of PD-L1 expression, and Cohort B, which included 52 mbc patients with PD-L1-positive tumors who received it as first-line therapy.

In Cohort A, Keytruda shrunk tumors by more than 30% in eight (5%) of 170 pre-treated patients, and stabilized the disease in 35 (21%) of pre-treated patients. Of the eight who experienced tumor reduction, all of them lived at least another year. The remaining patients in this cohort had a lower chance of survival. In Cohort B--those who received Keytruda as first-line therapy and had PD-L1 positive tumors, 12 (23%) of 52 patients saw tumors shrink by more than 30%, while the disease was stabilized in nine (17%) of them.Interestingly, based upon these results, PDL-1 expression did not impact patients outcomes for mbc patients with TNBC who took Keytruda.(As of June 2017, there are several actively recruiting Keytruda trials for mbc patients).From: https://www.eurekalert.org/pub_releases/2017-06/nlmc-ide060117.php

HER2 Negative, BRCA-Mutated MBC

Olaparib (Lynparza) (Not Yet FDA-Approved):A drug being studied for women with HER2 negative, BRCA-mutated breast cancer is the PARP inhibitor olaparib.Based upon the results of the randomized Phase 3 OlympiAD clinical trial consisting of 302 patients, progression-free survival (PFS) was 2.8 months longer for patients on Oliparib vs. patients on Physician's Choice chemotherapy, although Overall Survival (OS) was the same for both groups.Olaparib is an oral drug that appeared to be better-tolerated than chemotherapy.From: http://www.medscape.com/viewarticle/881079#vp_2

Information About "Biosimilar" Products:

The rapid increase in health care costs—most notably in cancer care and the price of cancer drugs in the United States—has prompted increasing consideration of options for containing the cost of cancer care. One recent strategy is the development of "biosimilars." Unlike generic medications, a biosimilar is a product that is highly similar but not identical to an approved therapy with no differences in efficacy, safety, or purity between the biosimilar and the reference product—except for minor differences in clinically inactive components.

The process by which biosimilars are approved makes it less likely that large phase III comparative clinical trials will be conducted. Therefore, preclinical and limited clinical data will need to be used to extrapolate the indications for which the original therapy was approved, and clinicians must decide on the appropriate incorporation of biosimilars.

Available data from Europe have not suggested that switching an approved therapy to a corresponding biosimilar leads to any safety or efficacy concerns. Currently, there are no biosimilars in the United States approved by the FDA as interchangeable with standard therapy.

In 2015, ASCO (the American Society of Clinical Oncology) issued a policy brief on biosimilars to provide guidance to its members and to policymakers on the evolving regulatory landscape of biosimilars. The policy brief articulated the following principles, among others:

•Biosimilar clinical trials should demonstrate efficacy and safety, including lack of immunogenicity.

•The FDA should establish a transparent regulatory pathway for approval of biosimilars.

•Physician choice between biologic products in the best interest of patients should not be restricted.

•Approved biosimilars should be subject to careful post-market safety surveillance.

•Interchangeability should be established by clinical trials that are adequately designed and performed to support substitution.

•Congress should ensure adequate FDA funding to meet new demands.

However, the field of biosimilars is still in its infancy within the US, and more information about these products is expected to be revealed over time.From: http://am.asco.org/biosimilars-changing-cancer-care-landscape

Chico

Thank you for putting this information out in a very readable format. I see my onc tomorrow and get results of my scan. Have done 9 cycles of Ibrance & Letrozole with Denosumab on a trial in the UK & am now experiencing lots of pain in my spine & sacrum where I have extensive mets. Hope I don't have to move on from this but my neuts are under 1 for the third time since starting out so at best I expect a dose reduction. However being armed with this info helps me "fight my corner" re any regime going forward.

Thank you Bestbird and great to see you back posting out really useful information.

Bestbird

Chico, I hope everything goes as well as possible during your visit! Also, please keep in mind that I keep my MBC Guide updated, so please feel free to request the most recent version any time you wish!

Moissy

Thanks for the incredible research and info that you share with us, Bestbird!

Chico

Thank you & I will request update once I know my results. Xx

PattyPeppermint

best bird. Thanks. Always appreciate your wealth of knowledge. Now I'll have to spend some time really figuring it out but seen some really positive stuff. Thanks

artistatheart

You are brilliant Bestbird! thank you...

pajim

Mille Grazie bestbird!

Groovywilma

Thank you for sharing this update! It is very very much appreciated!

Bestbird

It is so good to be able to share encouraging news!

momallthetime

Best BIRD - that's just such great info!

BEST BIRD - re triple positive, Dani is now on the trial DS8201a, she went trough many many treatments. New liver biopsy done a few wks ago. She has bone/liver and brain mets. peritoneal invasion... so Onco is sending out for F1 (2nd time in 2 yrs), and she requested PDL1 check. Cancer Center in NYC does not want to do it, bcs they said it's only for lung cancer. She is trying to have it sent to another lab.

My request from you, is where can you direct me for some literature in PDL1 for triple positive being helpful. In case DS8201a does not work for her, (she just started the trial), I'd like to be prepared. And would love to show Onco how there is some hope for her with immunotherapy. I read this article,

http://www.mdedge.com/oncologypractice/article/105... about Avelumab would that maybe be something?

Can you help us with this information. Thank you so much for all your hard work! And yes, I'll send you an email to request an updated version. Thanks.

momallthetime

Also, there seem to be triple negative trials but very few for triple positive.

LisaY

Thank you!

AnimalCrackers

Thank you Bestbird!  Your efforts are very much appreciated!

momallthetime

Bestbird got your wonderful addition, gonna try very hard to understand it. Thank you so so much.