Sunday, February 18, 2024

Maintenance Chemo For Ovarian Cancer

Maintenance Treatments After Recurrence

Chemo for Ovarian Cancer

This table lists the drugs most commonly used when cancer returns more than 6 months after the last platinum treatment and then responds again to platinum-based chemotherapy. These drugs are listed in the National Comprehensive Cancer Network guidelines as preferred treatment options. Treatment with these drugs generally starts about eight weeks after completing chemo. Please take this information to your doctor as an aid for your discussions.

PARP inhibitors, olaparib and niraparib were recently approved as maintenance therapy following first line treatment based on their effectiveness in preventing recurrence. Women with BRCA1 or 2 gene mutations detected in their blood or tumor received the most benefit from such treatment. Therefore, genetic testing for inherited cancer risk can be important even if there is no family history. If negative, tumor testing can be performed to determine if a BRCA mutation is found only in the tumor .

Less Repair More Benefit

In the phase 3 randomized trial, called ARIEL3, that led to the new approval for rucaparib, researchers led by Dr. Coleman enrolled 564 women with recurrent ovarian, fallopian tube, or primary peritoneal cancer. ARIEL 3 was funded by Clovis Oncology, Inc., the manufacturer of rucaparib.

All the women in the trial were responding, either completely or partially, to platinum-based chemotherapy. After testing participants’ tumors with the companion diagnostic test, the researchers randomly assigned 375 to receive rucaparib, which is given daily as a pill, and 189 to receive a placebo. Women continued treatment until their cancer progressed, they died, or they chose to discontinue treatment because of side effects or other reasons.

Overall, the women who received rucaparib lived a longer time without their cancer progressing than women in the placebo group: 10.8 months, compared with 5.4 months.

The benefit of rucaparib was stronger in patients with DNA repair defects, as measured by the companion diagnostic test. Women with HRD tumors who received rucaparib lived for a median of 13.6 months without their disease progressing. Women with BRCA mutations treated with rucaparib had a median progression-free survival of 16.6 months.

The ARIEL3 researchers are continuing to follow trial participants over time to see whether treatment with rucaparib improves how long women live overall .

Parpi In Brca Wildtype Tumors

While PARP inhibitors have traditionally been used in BRCA mutant tumors, recent trials have focused on the efficacy of PARP inhibition regardless of BRCA status. Recently, the FDA granted priority review and approval for frontline maintenance therapy to two PARP inhibitors, niraparib and olaparib in combination with bevacizumab based on the results from the PRIMA and PAOLA-1 studies respectively . Evidence of reduced but significant clinical benefit related to HRD status with olaparib/bevacizumab and all BRCA wildtype patients with niraparib was observed.

In the PRIMA study which enrolled patients with stage III or IV disease, PFS was increased from 13.8 vs. 8.2 in all patients treated with niraparib. Results were further stratified based on HRD status, patients who were BRCA wildtype with HRD tumors had greater PFS of 21.9 versus 10.4 months however BRCA wildtype homologous recombination proficient tumors demonstrated less advantage of PFS of 8.1 versus 5.4 months . Despite limited benefit of less than 3 months PFS and relatively high toxicity profile involving nearly 65% Grade 3/4 drug related adverse events, the FDA approved niraparib for frontline maintenance therapy in BRCA wildtype, HRD negative ovarian cancer patients .

Table 1

**Historical comparison 398/116,192=0.34%

A meta-analysis reported that risk of progression or death was reduced compared to placebo, however data regarding overall survival was not mature in the trial results analyzed .

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Is Maintenance Therapy A New Kind Of Cancer Treatment

No. But maintenance treatment has been proven to extend survival in more types of cancer than in the past. Maintenance therapy is now more effective and feasible for many types of cancer because:

  • The number of effective drugs for most types of cancer has increased because of ongoing advances in cancer research. It is not possible to use all of the effective drugs together as part of the first-line treatment, due to causing too many side effects. However, giving different drugs immediately after the initial treatment has achieved its maximum effect has improved survival in some types of advanced cancer. In general, the biggest impact from maintenance treatment is seen when a drug with a completely different way of attacking the cancer cell is introduced during maintenance therapy .

  • New cancer drugs often have fewer side effects than older ones. This means that people may be able to take them longer.

Cancer survivors have different feelings about maintenance therapy. Some people feel safer taking maintenance therapy. But others may feel that they are not a “cancer survivor” if they are still receiving ongoing treatment. Learn more about survivorship, including the challenges of receiving extended treatment. And, talk with your health care team about finding emotional support that is right for you.

How Can I Reduce My Risk Of Developing Ovarian Cancer

Ovarian Cancer

Maintaining a moderate weight and not smoking may help reduce your risk of developing ovarian cancer.

If youre considered to have a higher risk for this type of cancer, you can talk with your doctor about other risk-reducing strategies, such as:

  • taking birth control pills
  • surgically removing your ovaries

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Incorporating Maintenance Treatment Into Daily Life

Sticking to a medication schedule is important to make sure the treatments work as effectively as possible. If you miss doses, there may be negative effects.

  • The treatment may not work as well.
  • Cancer may be more likely to return or worsen.
  • You may need more frequent doctors visits.

Its crucial to take maintenance treatment at the right times, exactly as directed, and using the correct dose.

Unfortunately, sticking to a cancer treatment plan may be difficult for many reasons. A person may experience side effects, have a hard time understanding the medication instructions, be distracted by life activities or events, forget doses, or have a hard time affording the cost of medication. Fortunately, there are many ways to minimize these barriers.

Treatment Considerations For Parp Inhibitors In First

This article reviews emerging evidence on PARP inhibitors as first-line maintenance treatment options after chemotherapy and features expert insights from Rebecca Previs, MD.

KEY TAKEAWAYS:

  • Despite available treatments, 85% of patients with advanced ovarian cancer will experience recurrence at some pointafter chemotherapy.
  • For patients with advanced ovarian cancer, emerging evidence shows that poly polymerase inhibitors are effective for first-line maintenance after chemotherapy.
  • The choice of first-line maintenance therapy in patients with advanced ovarian cancer should be individualized based on molecular status and initial therapy.

Ovarian cancer is the fifth most common cause of cancer deaths in women and the leading cause of death among cancers of the female reproductive system in the United States. More than 21,400 women in the United States are expected to be diagnosed with the disease in 2021, and 13,770 will die from it.1 Up to 90% of ovarian cancer cases are epithelial in origin, and 7 of every 10 epithelial ovarian cancers are high-grade serous tumors.2

The concept of maintenance is to enable patients to have a higher rate of cure and to prevent the cancer from coming back, because we know once a cancer comes back, its even more difficult to treat.

Choosing a Maintenance Therapy

Latest Data on PARP Inhibitors

Adverse Events and Dosing

An Emerging PARP Inhibitor

Looking Forward

REFERENCES

Editors Note: Interview quotes slightly modified for readability.

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Moving The Needle For Maintenance Cancer Treatment

CURE

Maintenance therapy helps deter undetectable cancer that may exist after initial treatment.

Successful management of cancer requires treatment planning based onthe best science available.

Our growing knowledge of the biology of cancer has led to many refinements and innovations to surgery, radiation and medical treatments. Carefully designed, conducted and interpreted results from clinical trials testing each of the therapeutic components and modifications are needed to prove better outcomes either a long-term cure, extension of survival or at least some control of the cancer and/or enhanced quality of life.

It is not uncommon to extend part of a patients medical therapy to address the possibility of cancer that we cannot see or even test for microscopic cancer cells that in some cases lay dormant for many years . This approach is called maintenance therapy and is addressed in more detail in this issue of CURE®, focusing on its application in ovarian cancer.

In many cases, maintenance therapy includes less-intense components ofthe initial treatment.

For most malignancies, we currently do not have good ways to detect and measure microscopic cancer cells that could lead to recurrence and death. That is changing with newer technology, particularly the ability to assess and quantify tumor DNA circulating in the bloodstream.

As the case with ovarian cancer proves, we can incrementally move the needle as maintenance therapy continues to evolve.

Targeted Therapy For Ovarian Cancer

NCCN Animation for Patients: Maintenance Therapy After Initial Treatment for Ovarian Cancer

Cancer occurs when genetic mutations in our cells cause them to multiply uncontrollably and accumulate to form a tumour. Targeted cancer therapies are drugs that stop the spread of cancer by identifying and blocking the genetic changes responsible for the cancers growth and progression.

There are different targeted therapies available to women with ovarian cancer. Find out whether youre eligible and how to access these treatments.

Ovarian cancer drug: Avastin

Avastin belongs to a group of treatments called anti-angiogenics. These treatments stop cancer from developing new blood vessels. This restricts the supply of food and oxygen to the cancer, which means it is starved and unable to grow.

In England, Avastin is used to treat first-line ovarian cancer following the standard treatment combination of Carboplatin and Paxitaxol. It is available through the Cancer Drugs Fund only to patients with advanced ovarian cancer as a maintenance drug, which means it aims to prevent or delay the cancers return.

In Scotland, Avastin is available for women with recurrent, platinum resistant ovarian cancer.

You can read about the different side-effects of Avastin here.

PARP inhibitors

PARP inhibitors are a new class of targeted cancer drug that is becoming more common in ovarian cancer treatment.

There are currently three PARP inhibitors available to treat ovarian cancer: olaparib, niraparib and rucaparib.

Ovarian cancer drug: Olaparib

Ovarian cancer drug: Niraparib

What is HRD?

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Future Paths For Parp Inhibition

As clinicians become more comfortable using companion diagnostics to measure HRD and other biomarkers to gauge the potential vulnerability of a tumor to PARP inhibition, “they could end up being important decision-making tools,” said Dr. Coleman.

Future trials will likely look at administering PARP maintenance therapy sooner in ovarian cancer treatment, after initial therapy , Dr. Coleman explained.

Researchers are also interested in testing PARP inhibitors as an initial, or first-line, treatment in both BRCA-positive and BRCA-negative ovarian cancers, continued Dr. Coleman.

Research in PARP inhibitors has also been expanded to include combinations with immunotherapies, such as immune checkpoint inhibitors, and with targeted therapies, like cediranib, explained Dr. Kohn. “There’s a huge looking at how to leverage the activity of PARP inhibitors in combination therapies. That’s the next step,” she said.

Many of these trials are based on new knowledge of DNA repair mechanisms that has been gleaned from studying why some tumors are resistant to PARP inhibition, which in turn has led to the development of new drugs targeting DNA repair, she continued.

“It’s a really nice circle thats been a welcome development,” concluded Dr. Kohn.

What Is Maintenance Therapy

About 80% of women who are diagnosed with ovarian cancer will go into remission after their initial treatment, but around 60% will then have a recurrence. The goal of maintenance therapy is to delay a cancer recurrence or to reduce the risk of it recurring at all. It involves using specialized medications to maintain remission.

Maintenance therapy can usually be started right after the initial surgery and chemotherapy are complete.

Maintenance therapy after first-line chemotherapy may be the best opportunity to improve prognosis, Mantia-Smaldone said. We hope that by starting these agents after the final cycle of front-line chemotherapy, we can improve prognosis beyond five years.

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Ask Your Doctor If Maintenance Therapy Might Help

Your oncologist can help you better understand which cancer treatments may be most likely to help you. If youve already gone through initial front-line therapy such as chemotherapy, maintenance therapy may be able to help keep cancer under control and give you more time before the cancer comes back. In some cases, maintenance treatments may help women live longer.

Targeted Drug Therapy For Ovarian Cancer

Can advanced

Targeted therapy is a type of cancer treatment that uses drugs to identify and attack cancer cells while doing little damage to normal cells. These therapies attack the cancer cells’ inner workings the programming that makes them different from normal, healthy cells. Each type of targeted therapy works differently, but they all change the way a cancer cell grows, divides, repairs itself, or interacts with other cells.

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When Does Treatment Start

Treatment will usually be recommended when your team has found clear evidence of the cancer growing on scans. Sometimes your CA125 blood test may be rising without any other sign of cancer activity . Its unlikely your team will recommend starting treatment based only on a raised CA125 level. Thats because research has shown that starting chemotherapy when your CA125 levels starts rising doesnt have an effect on how successful the treatment is. Also a raised CA125 level isnt enough on its own to prove that the ovarian cancer has come back.

Waiting until you have symptoms or until there are signs of more significant tumour growth on scans can be worrying if you want to start treatment as soon as possible, but there are benefits to waiting:

  • it means you have a longer period between platinum-based chemotherapy treatments . This may mean you respond better to the drugs and it reduces the chances of your body developing resistance to the treatment.
  • it may improve your quality of life, because if the cancer comes back again over the course of time, you’ll spend less time having treatment and dealing with the side effects.

Its also okay to start treatment as soon as its been confirmed that the cancer has come back. Its important for you to talk with your clinical nurse specialist or oncologist about what you want to do, as you may have a particular reason for wanting to start treatment as soon as possible.

Chemotherapy For Germ Cell Tumors

If you have a germ cell tumor, you will likely be treated with combination chemo . The combination used most often is called BEP, and includes the chemotherapy drugs bleomycin, etoposide and cisplatin . If the cancer is a dysgerminoma, these are usually very sensitive to chemotherapy, and can sometimes be treated with the less toxic combination of carboplatin and etoposide. Other drug combinations may be used if the cancer isnt responding to treatment or to treat cancer that has recurred . These include:

  • High dose chemotherapy

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What Patients With Ovarian Cancer Should Know About Maintenance Therapy

Maintenance therapy is meant to prevent relapse after a patient with ovarian cancer received their main treatment. Heres an overview of what patients should know.

When a patient is diagnosed with ovarian cancer, their initial treatment typically consists of a combination of surgery and chemotherapy, after which most enter remission.

Then the question is, should we consider maintenance therapy? said Dr. Kathryn Pennington, a gynecologic oncologist at the University of Washington, in a presentation at the 12th Annual Joining FORCEs Against Hereditary Cancer Conference.

Understanding the Goals of Maintenance Therapy

Maintenance therapy is the treatment a patient receives after they complete chemotherapy. It is intended to decrease the chance their cancer will return or to delay it from returning. The goal is to continue or maintain, its namesake the successful results of a prior treatment.

When a patient receives maintenance therapy after first-line chemotherapy, it can significantly delay the time of cancer recurrence and avoid the need for second-line chemotherapy. If they do end up having a recurrence after maintenance therapy, maintenance therapy can continue after second-line chemotherapy if patients have a good response.

Maintenance Therapy Options and Recent Approvals

There are several available options for maintenance therapy that have been approved by the Food and Drug Administration in epithelial ovarian cancer, Pennington explained.

Observation Or Watch And Wait

Adjuvant Chemotherapy Bevacizumab for Ovarian Cancer

Previously, the only option for women after their cancer fully or partially responded to chemotherapy was to observe the disease, or watch and wait8 to see if it came back. This approach involves regular doctor visits for tests to monitor disease, rather than taking medicine.9 Today, those impacted by ovarian cancer have more choices than to “watch and wait” for the disease to return. It is important to discuss options with your doctor, to initiate maintenance therapy early when facing the disease.

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Keeping Ovarian Cancer From Returning: What To Know About Maintenance Therapy

Being told you have ovarian cancer is overwhelming and can be particularly scary. The disease has a reputation for being extremely aggressive with low survival statistics when caught in its later stages. But that reputation is changing. Many women are living longer than ever after their diagnosis. Treatments for ovarian cancer are evolving, and something called maintenance therapy is helping to slow or stop the cancers return.

Here, Gina M. Mantia-Smaldone, MD, a gynecologic oncologist at Fox Chase Cancer Center, answers common questions about maintenance therapy for ovarian cancer.

Frontline Treatment And Recurrence

Platinum resistant patients are defined as recurrence < 6 months after the last dose of platinum therapy. These patients are typically treated with pegylated liposomal doxorubicin, topotecan, gemcitabine, paclitaxel or experimental therapy. These systemic therapies can be considered alone or in combination with bevacizumab. The Aurelia Phase III study investigated the use of bevacizumab with chemotherapy in platinum resistant ovarian cancer . Although the study reported significantly longer PFS and ORR compared to single agent chemotherapy, results exhibited moderately significant drug related toxicity related to the addition of bevacizumab.

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