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

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


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