#gyncsm Community: July 2019

Friday, July 12, 2019

Highlights of the #CANCERSM - Basics of Biomarker Testing Chat

We joined with the #lcsm, #bcsm, and #btsm Twitter Communities and Dr.Tim Allen (@TimAllenMDJD) for this important discussion on Biomarkers. The chat focused on molecular biomarkers for cancer.

You may find the transcript here .

Below are a few highlights from last night's chat. Resources may be found at the end of the post.

T1: What is a biomarker and how is it identified?

T1 A biomarker is a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease.
T1 A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Also called molecular marker and signature molecule.
T1 Tumor markers, which are a type of biomarker, have traditionally been proteins or other substances that are made by both normal and cancer cells but at higher amounts by cancer cells.
T1 Tumor markers provide information about a cancer, such as how aggressive it is, whether it can be treated with a targeted therapy, or whether it is responding to treatment:
T1 A biomarker can be predictive of treatment response or prognostic for disease course independent of treatment
basic info on Wikipedia: https://t.co/CfEcQ77LCv.
T1 Cancer researchers are working to develop new biomarkers that can be used to identify cancer in its early stages, to predict the effectiveness of treatment, and to predict the chance of cancer recurrence.
T1: In the brain tumor community, biomarkers are how we patients introduce ourselves to each other. No longer do we talk about the types or grades (i.e. stage) of our tumors, we talk about our biomarkers. For reals.

T2: What is biomarker testing used for?

T2 There are two main types of tumor markers that have different uses in cancer care: circulating tumor markers and tumor tissue markers.
T2 Molecular biomarker tests are generally of three types of biomarkers: diagnostic, therapeutic, prognostic
T2 Circulating tumor markers, which can be found in the blood, urine, stool, or other bodily fluids of some patients with cancer, are used, for example, to estimate prognosis and to assess the response to treatment.
T2: Molecular biomarker testing involves laboratory tests that evaluate and identify the presence, on the surface of a cancer cell for e.g. a protein, or the identification of mutations or other changes in the cancer cell genes
T2 Tumor tissue markers, which are found in actual tumors, are used to diagnose, stage, and/or classify cancer, to estimate prognosis, and to select an appropriate treatment (e.g., treatment with a targeted therapy)
T2: In cancer, biomarker testing is analysis of DNA, RNA, or proteins that provide info about the diagnosis, prognosis, or are predictive for response to treatment
T2 An example of a diagnostic biomarker is prostate-specific antigen (PSA) used for screening of prostate cancer. An example of a therapeutic biomarker is EGFR gene testing in patients with lung cancer.
While the traditional breast carcinoma prognostic markers ER, PR, Her 2 neu predicts whether a patient will need hormonal therapy or chemotherapy or Herceptin, more recently in April 2019, immunotherapy has been approved by FDA in triple negative breast ca patients
Many non-small cell #lungcancer people also identify with biomarkers--EGFR, ALK, ROS1, BRAF, NTRK, KRAS, RET ....
T2: Diagnostic biomarkers help in the diagnosis of the cancer itself; therapeutic biomarkers help in determining whether or not a patient might respond to a molecular therapy; and prognostic biomarkers help determine the patient’s chances for long-term survival.
T2: Here's an overview of what is being studied for #ovariancancer Diagnostic and Prognostic Biomarkers in ovarian cancer and the potential roles of cancer stem cells – An updated review https://t.co/Lo7npjtVOw

T3: What treatment options can be identified through biomarker testing?

T3 A number of tumor markers are currently being used for a wide range of cancer types. Here’s a list of tumor markers in common use: https://t.co/NtPLX1lStR
T3 In breast cancer, testing tumors for estrogen and progesterone receptors and the HER2 protein can help doctors help determine whether treatment with hormone therapy or some targeted therapies is appropriate.
T3 In non-small cell lung cancer, an analysis of mutations in the EGFR gene can help doctors determine a patient’s treatment and estimate prognosis.
T3: identifying #NTRK fusion in #glioma (est 1% of gliomas) opens up avenues for 2 therapies #btsm
T3 in lung cancer oncogenic alterations in EGFR ALK ROS1 RET et cetera determine treatment choicces
T3 In many types of cancer, seeing whether the tumor makes the PD-L1 protein can determine whether treatment with a type of #immunotherapy drug called an immune checkpoint inhibitor is appropriate.
T3: and... finding #H3K27m mutations opens the door to try drugs like #ONC201 (as seen at #ASCO19
T3: SO MANY OPTIONS can be identified through biomarkers. Hormone therapy, immunotherapy, targeted kinase inhibitors, antibodies like herceptin... They can also point to clinical trials
Analysis of mutations in EGFR+ NSCLC (and other oncogene-driven cancers) can also help determine how to treat resistance to targeted therapies.
In myeloma the expression of BCMA is used as a biomarker for CAR-T cell therapy
T3: If the molecular biomarker testing shows that the patient's cancer contains the therapeutic target, then that patient might benefit from treatment with the corresponding drug. This is personalized medicine!
T3 These drugs, like all drugs, have side effects, so beyond the needless cost, it is important to not treat patients with these molecular therapies if the biomarker testing shows that the drug would not benefit the patient

T4: What biomarker tests should be run for which types of cancers? What is a liquid biopsy and when is useful?

T4 There are guidelines for what biomarker testing must be performed on different cancer types. https://t.co/0NmT5EaL4E
T4: "Liquid biopsy" refers to molecular biomarker testing performed not on a patient's cancer tissue, but on cancer cells or cancer cell DNA or RNA that is floating in the blood stream.
T4 For lung cancers, the minimum testing that must be performed is to look at the EGFR gene for mutations and ALK1 and ROS genes for rearrangements. Many pathologists examine other more recently recognized mutations.
T4 A #liquidbiopsy is a test done on a sample of blood to look for cancer cells from a tumor that are circulating in the blood or for pieces of DNA from tumor cells that are in the blood.
T4 For colon cancers, RAS gene testing to guide anti-EGFR therapy. BRAF mutational testing should also be performed for prognostic information.
T4 For Breast cancers, the pathologist performs testing for estrogen receptor, progesterone receptor, and HER2 by immunohistochemistry
T4 A liquid biopsy may also be used to help plan treatment or to find out how well treatment is working or if cancer has come back. Taking multiple samples of blood over time may also reveal the molecular changes taking place in a tumor.
T4 From NCI’s Cancer Currents blog last year: Liquid biopsy may predict the risk of breast cancer returning years later: https://t.co/zuL4GnA0CV
T4: Liquid biopsy is used in cases where a biopsy of a patient's cancer cannot be performed because the patient is too ill to tolerate the diagnostic procedure, or where the cancer site is difficult to access with a biopsy e.g., a lesion deep inside the body
T4 And here’s an overview from 2017 of the evolving science around liquid biopsies and the important research questions: https://t.co/zqj48vhMbG
T4: I love the quote about liquid biopsies-- It's like looking for a needle in a haystack. If you find a needle, it's a needle. But if you don't find the needle, it doesn't mean one's not there. A negative result always needs to be followed up by testing tissue
Most liquid biopsy tests are not yet covered by insurance. However, most test manufacturers can provide some financial assistance.

T5: Can and should patients pursue biomarker testing for treatment options if their doctor does not offer it?

Yes! Push for best care possible. It's my oncologist's job but it's my life
T5 NCI does not have guidelines for the use of tumor markers. However, some national and international organizations have guidelines for the use of tumor markers for some types of cancer: https://t.co/o85pqHZKoy
T5: Molecular testing and molecular therapy has become the standard of care for many cancers. Most doctors are performing the recommended molecular testing on particular types of cancer.
T5 absolutely! doctor should always point out all possible options even if not available at his/her own institution
As @JFreemanDaily bought up, the NCCN guidelines are a great resource and an excellent place for patients to find out what the current recommendations are and ask questions of their doc's if there is a variance https://t.co/X5OVXPY9g6
T5 The basic question to ask your doctor is "Given my diagnosis, is molecular biomarker testing is right for me?" You can read about guidelines which are specifically designed for patients at
https://t.co/yyMAKwn2RK
T5: Second opinions are almost always a good idea - especially in cancer. Seek doc's with high case volume of your specific type of cancer. You are you own best advocate and the science is changing fast
T5: It's always a good idea to ask your doctor about molecular testing; but given the confusion in this rapidly changing area, it may be difficult to know what to ask your doctor. Feel free to call your pathologist and discuss!
Get your pathology report and usually there's a phone number. If not, your hospital or clinic should be able to provide

We are so glad that #gyncsm could be an part of this important discussion.

Dee
#gyncsm co-founder

Resources
Kyle Strimbu and Jorge A. Tavel, M.D. What are Biomarkers? (2011) https://t.co/CV1ROepZnS

NIEHS: Biomarkers https://t.co/cNuwLouCPJ

FDA: BIOMARKER TERMINOLOGY: SPEAKING THE SAME LANGUAGE https://t.co/Ua6gPOZevl

FDA: What Are Biomarkers and Why Are They Important? Transcript https://t.co/Ndpiy1XWlp

lay friendly overview https://t.co/GnpK7bWJkm #cancersm @CancerDotNet

This is a great slide. #MMSM #Biomarkers https://t.co/XvmjWfL296

Salivary Biomarkers: Toward Future Clinical and Diagnostic Utilities https://t.co/Q4bzv0UQoc

Salivary biomarkers and proteomics: future diagnostic and clinical utilities https://t.co/Epp0cUOsdq

VOC breath biomarkers in lung cancer (2016) https://t.co/TmvUTPyxkp Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening (2015) https://t.co/ccpsi93wS2

MIT Tech Review: Liquid Biopsy Fast DNA-sequencing machines are leading to simple blood tests for cancer. (2015) https://t.co/hw4kQVftKq

Biopsia líquida https://t.co/jsmZvQYM8H

Thursday, July 11, 2019

#CANCERSM Chat - Basics of Biomarker Testing 7/11/19

Please join us on Thursday, July 11, 2019 at 8:00pm for a joint Cancer hashtag community chat featuring Pathologist Dr. Timothy Craig Allen (@TimAllenMDJD).

Until just a few years ago, chemotherapy was often the only option for some cancer patients. In just a few short years, molecular therapies and immunotherapies have become commonplace as treatments for cancer patients. But determining whether a particular cancer patient is a candidate for these new, often very expensive, molecular and immunotherapies requires molecular biomarker testing. For many cancer patients and their families, the role of molecular biomarker testing in their diagnosis is an unfamiliar and confusing. How is testing performed? How is the test result analyzed? What is involved in getting helpful answers from biomarker testing? Does liquid biopsy have a role?

Pathologists are specialized doctors responsible for answering these questions. They identify any cancer cells in the biopsied specimen, and guide the patient’s biomarker testing. Unfortunately, pathologists do not typically speak with patients, so patients and families–and even some doctors–often do not have a clear understanding of the role of molecular biomarker testing in the diagnosis and treatment of cancers. Learning more about the basics of biomarker testing can help patients and families cut through the hype about biomarker testing, understand the patient’s specific disease more thoroughly, and learn what biomarker test results mean to the patient’s cancer treatment.

Please join moderator and pathologist Dr. Timothy Craig Allen (@TimAllenMDJD) at 8 PM Eastern Time on Thursday, July 11, 2019, for a discussion about the basics of biomarker testing, a subject potentially affecting all cancer patients and doctors.

We will cover the following topics:

T1: What is a biomarker and how is it identified?
T2: What is biomarker testing and what is it used for?
T3: What treatment options can be identified through biomarker testing?
T4: What biomarker tests should be run for which types of cancers? What is a liquid biopsy and when is useful?
T5: Can and should patients pursue biomarker testing for treatment options if their doctor does not offer it?

Please remember to include #cancersm in ALL your tweets so the other chat participants can see them.

If you need a refresher, read the #LCSM primer on participating in a Twitter chat (the hashtag in your tweets will be #cancersm, not #LCSM). Note that some tweetchat apps (like tchat.io) will not display tweets longer than 140 characters. Hope you’ll join us!

Dee and Christina

Co-founders #gyncsm

Wednesday, July 10, 2019

Maintenance Therapies for Gyn Cancers - July 2019 Chat

This month's chat was a new but important topic for us to discuss - Maintenance Therapies for Gyn Cancers. Thank you to all our Twitter friends who promoted and joined in this chat.

We had 19 participants, including patients who have been on maintenance, advocates and physicians. You may find more analytics here and the transcript here. As always a list of resources can be found at the bottom of this page.

T1: What are maintenance therapies and why are they used?

@theNCI def: maintenance therapy is given to help keep cancer from coming back after it has disappeared following the initial therapy. It may include treatment with drugs, vaccines, or antibodies that kill cancer cells, and it may be given for a long time.
A1 Maintenance therapies are additional chemotherapy given beyond the standard chemotherapy. The philosophy is based on treatment for hematologic cancers and is now used for some solid tumors. The hope is that the additional treatment will prevent or delay recurrences.
The goal of maintenance therapy is to prevent recurrence or increase the time to next therapy with less side effects than chemotherapy
The downside of maintenance therapy is that patients may experience toxicity and a decriment in quality of life while on a maintenance program. Neuropathy was the reason that Taxol maintenance did not become a standard of care after 2 clinical trials in ovarian cancer. Also the initial benefit seen in survival was no longer apparent after patients were followed for longer time periods

T2A: What evidence was there to approve Avastin (Bevacizumab) for maintenance?

T2B: How long is Bev given? What side effects may women experience with maintenance Bev? Is Bev limited to women with a BRCA mutation?

Numerous clinical trials from American and European consortiums have demonstrated benefit of bevacizumab in the maintenance setting in Gyn cancers. (Gog252)
FDA Approval was based on GOG-0218 a multicenter, randomized, double-blind, placebo-controlled, three-arm study w/ addition of bev to carbo Taxol for patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer
A2B in the US trial bevacizumab was given as maintenance for 15 cycles 3 weeks apart. Although an initial survival benefit was seen this was not sustained with longer followup. A similar trial was conducted in Europe with similar results.
In the maintenance phase, bevacizumab can be given up to an extra year of treatment. It is still unclear whether we should be giving this longer as no clinical trials have administered the drug longer than this. I have a personally treated patients for many years.#gyncsm
A2B Bevacizumab is generally well tolerated - some patients may have high blood pressure or kidney problems. More severe side effects are rare but possible.
Bevacizumab as maintenance is another therapy available for select women with #ovariancancer. Recommendations must be personalized to a specific patient (getting the right drug to the right patient at the right time
For anyone with gyn #sarcoma: Bevacizumab (Avastin) failed in a study of women with uterine #leiomyosarcoma, but some doctors are considering other combinations with it.

T3A: PARP inhibitors were approved for recurrent ovarian cancer and now for maintenance therapy for women with the BRCA mutation. What study results led to the FDA approval?

T3B How long is PARP given during maintenance? What side effects may women experience?

You can get an overview of PARP inhibitors for maintenance therapy of ovarian cancer via @FacingOurRisk site https://t.co/DNA0tsgoeN
T3A One study used was phase III SOLO1 trial (NCT01844986) assessed maintenance olaparib/placebo treatment following first-line platinum-based chemotherapy
T3A Frontline maintenance olaparib treatment was approved by the FDA in December 2018 for BRCAm carriers
T3B: PARP truly can be used until progression, or side effects make the patients want to stop. Biggest SE I see are GI and heme (bone marrow). Some recent eye changes...which is a new one!
T3B the length of parp maintenance will depend on the clinical scenario (up front or recurrent) as well as the patient's tolerance to the medications
Clinical trials proves a 21 month progression free survival for each of the PARP inhibitors: olaparib, rucaparib
The treatment is generally given until either the disease progresses where the patient cannot tolerate side effect. The side effects are different among each of the agents but generally fall into the realms of low blood counts, fatigue, nausea, in general malaise.
Some women with gyn #leiomyosarcoma use #trabectedin (#Yondelis) as maintenance therapy. They and women with endometrial stromal #sarcoma may use hormone therapy. (I took an aromatase inhibitor for about 5 years.)

T4: Are maintenance drugs given for other gyn cancers? Cervical, endometrial, etc?

No maintenance strategies are currently approved for endometrial cancer but a trial evaluated carboplatin and paclitaxel for six cycles with and without trastuzumab in high-grade serous endometrial cancer with Her2/neu overexpression.The study demonstrated a significant improvement in PFS Time will tell if OS will also improve
T4: No maintenance for Endometrial or Cervical—Except in those with mutations that they can use Keytruda—which is “kinda of” a maintenance
Yes. Maintenance with bevacizumab is standard for cervical and endometrial cancers as well as ovarian/fallopian tube/primary peritoneal cancers.

T5: What questions should a patient ask when offered a maintenance therapy?

Am I a good candidate for maintenance therapy? Which maintenance therapy is best for my cancer? How will we know when is the right time to stop treatment?
Some I would ask include: what are the side effects of long term use of the treatment? Will I be able to use this again if I recur? How much is the cost? And will my insurance cover it?
Cost can be a real burden with maintenance therapies. Important to ask so that risks and benefits can be weighed.
Women with gyn #leiomyosarcoma should ask to see the evidence for aromatase inhibitors, not just accept anecdotal information. For example, the fact that I did it is not proof it worked.
At #ASCO19 @Atul_Gawande spoke on asking patients about THEIR goals. This is the key with maintenance—what does your patient want? What is their goal?

Some information shared in this chat on Maintenance therapies appeared in @ASCO Educational Book article titled Wanna Get Away? Maintenance Treatments and Chemotherapy Holidays in Gynecologic Cancers https://ascopubs.org/doi/full/10.1200/EDBK_238755

We hope you will join and spread the word about the all-cancer chat #CancerSM on Thursday July 11, 2019 at 8pmET on the Basics of Biomarker Testing with @TimAllenMDJD .

Be sure to mark your calendar and join us for next month's chat Wednesday, Aug 14th on Finding Balance: “Cancer Life” vs. “Real Life”.

Dee
#gyncsm Co-founder

RESOURCES

Wanna Get Away? Maintenance Treatments and Chemotherapy Holidays in Gynecologic Cancers https://ascopubs.org/doi/full/10.1200/EDBK_238755

FORCE @FacingOurRisk site https://www.facingourrisk.org/understanding-brca-and-hboc/information/cancertreatment/ovarian-treatment/basics/maintenance-therapy-ovarian-cancer.php

NCCN updates from annual conference AJMC re: bev and parps https://www.ajmc.com/conferences/nccn-2019/nccn-ovarian-cancer-guidelines-add-options-for-parp-inhibitors-bevacizumab

Cost of maintenance therapies https://pharmaintelligence.informa.com/resources/product-content/how-ovarian-cancer-maintenance-therapies-stack-up-on-costs-and-value

Sunday, July 7, 2019

July 10, 2019 Maintenance Therapies for Gyn Cancers

Over the past few years the approval of maintenance therapies in gynecologic cancers have increased. The recent ASCO Annual meeting held a full session titled Wanna Get Away - Maintenance Treatments and Chemo Holidays in Gyn Cancers which included maintenance therapies for women diagnosed with gynecologic cancers. Women with High Grade Serous Ovarian Cancer (HGSOC) may choose to use Bevacizumab or PARP inhibitors as maintenance therapies. Women with Low Grade Serous Ovarian Cancer (LGSOC) may be offered hormonal treatment. Research into using maintenance therapies with endometrial and other gyn cancers continues.

On Wednesday, July 10, 2019 at 9pm ET (8pmCT, 6pmPT) join the #gyncsm community as we discuss the use of maintenance therapies for gyn cancers. Learn what treatments are available for your gyn cancer and what questions you should ask when considering maintenance therapy.

Chat topic Questions:
T1: What are maintenance therapies and why are they used?