Lynparza In Combination With Abiraterone Granted Priority Review In The Us For Patients With Metastatic Castration
First PARP inhibitor to demonstrate clinical benefit in combination with a new hormonal agent irrespective of homologous recombination repair genemutations
WILMINGTON, Del., August 16, 2022—-AstraZenecas supplemental New Drug Application for LYNPARZA® in combination with abiraterone and prednisone or prednisolone has been accepted and granted Priority Review in the US for the treatment of adult patients with metastatic castration-resistant prostate cancer .
LYNPARZA is being jointly developed and commercialized by AstraZeneca and Merck & Co., Inc., known as MSD outside the US and Canada.
The Food and Drug Administration grants Priority Review to applications for medicines that offer significant advantages over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the fourth quarter of 2022.
In the US, prostate cancer is the second most common cancer in male patients and is projected to cause approximately 35,000 deaths in 2022.2 Overall survival for patients with mCRPC is approximately three years in clinical trial settings, and even shorter in the real world.3-6 Approximately half of patients with mCRPC may receive only one line of active treatment, with diminishing benefit of subsequent therapies.6-11
IMPORTANT SAFETY INFORMATION
There are no contraindications for LYNPARZA.
Physical Emotional And Social Effects Of Cancer
Cancer and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative care or supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the cancer.
Palliative care focuses on improving how you feel during treatment by managing symptoms and supporting patients and their families with other, non-medical needs. Any person, regardless of age or type and stage of cancer, may receive this type of care. And it often works best when it is started right after a cancer diagnosis. People who receive palliative care along with treatment for the cancer often have less severe symptoms, better quality of life, and report that they are more satisfied with treatment.
Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies. You may also receive palliative treatments similar to those meant to get rid of the cancer, such as chemotherapy, surgery, or radiation therapy.
Institute Contributions To Publications
The top 20 most productive institutes from 1979 to 2018 are listed in Table Table2:2: three of these institutes are based in the UK, two are in Canada, and the rest are in the USA. This distribution reiterated the predominance of the USA in the research field of MCRPC. As the most historical and largest private cancer center in the world, Memorial Sloan Kettering Cancer Center contributed 208 publications, more than any other institution, accounting for 5.087% of the world’s publications in this field, and these publications were accompanied by 22,064 citations. The University of California San Francisco was second in productivity, with 181 publications and a total of 17,523 citations. The University of Washington and the University of Michigan ranked third and fourth, respectively. Regarding the h-index, Memorial Sloan Kettering Cancer Center also ranked first, followed by the University of Michigan and University of Washington. The institutions with high h-indexes were mainly from the USA, the UK and Canada, indicating that these countries had outstanding academic institutions and capabilities in this field of MCRPC.
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How Prostate Cancer Is Treated
In cancer care, different types of doctorsincluding medical oncologists, surgeons, and radiation oncologistsoften work together to create an overall treatment plan that may combine different types of treatments to treat the cancer. This is called a multidisciplinary team. Cancer care teams include a variety of other health care professionals, such as palliative care experts, physician assistants, nurse practitioners, oncology nurses, social workers, pharmacists, counselors, dietitians, physical therapists, and others.
The common types of treatments used for prostate cancer are described below. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care.
Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, and the patients preferences and overall health.
Cancer treatment can affect older adults in different ways. More information on the specific effects of surgery, chemotherapy, and radiation therapy on older patients can be found another section of this website.
Because most prostate cancers are found in the early stages when they are growing slowly, you usually do not have to rush to make treatment decisions. During this time, it is important to talk with your doctor about the risks and benefits of all your treatment options and when treatment should begin. This discussion should also address the current state of the cancer:
Evidence For Persistent Androgen Dependence
Studies have suggested, even in the presence of castrate levels of androgen, androgen levels in the prostate of men with CRPC still remain nearly equivalent of those in non-castrate patients . The source of these androgens is thought to be derived from synthesis of the androgens directly in prostate cancer cells due to an upregulation of the enzymes necessary to synthesize androgens such as testosterone and dihydrotestosterone . These findings suggest that prostate cancer that recurs despite castrate serum testosterone levels is not truly androgen-independent.
Several other mechanisms also may result in activation of the AR in prostate cancer in the face of castrate levels of androgen. These include increased AR expression through gene amplification and other mechanisms , mutations of the AR that can affect its ligand promiscuity, and molecular cross-talk with other signaling pathways and co-regulators that lie downstream of the AR .
Multiple pathways may be amenable to therapeutic intervention for patients with CRPC. In view of the persistence of both AR and tissue androgens in recurrent prostate cancer, therapies that directly target the AR, or affect the persistence of androgens in prostate tissue, may be of value for patients with CRPC . However, additional therapeutic strategies, including chemotherapy and immunotherapy, also have demonstrated benefit in CRPC, particularly in terms of the most important outcome of improved survival.
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Contributions Of Leading Authors
Many scientists from a wide range of origins have researched MCRPC and published their findings in the WoS. The top 15 authors in MCRPC research are listed in Table Table3.3. The most prolific author on the topic was de Bono, JS, who published 132 scientific articles and had a total of 16,423 citations. In addition, the author with the highest number of citations and the most citations per article published was Scher, HI, who had 115 articles and 17,978 citations. In the top 15 authors, de Bono, JS was the only author from the UK Fizazi, K was from France Saad, F and Chi, KN were from Canada Scher, HI and the other top 10 scientists were American. These institutions where these scientists worked were generally among the top 20 most productive institutions. For example, de Bono, JS worked at the Institute of Cancer Research, and Scher, HI worked at Memorial Sloan Kettering Cancer Center. In addition to these top scientists, there were more than 16,000 scientists in the world researching MCRPC.
An Analysis Of The Most Cited Papers
Although multiple indicators were used to evaluate the impact of scientific publications, citation counts are still an important measurement of influence in this research field.120,121 The top 20 most cited publications in the MCRPC research field during 19812018 are presented in Table Table8.8. The most highly cited paper was Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer. This article was published in the New England Journal of Medicine in 2010 by Kantoff, PW and headed the lists of total citations and annual citations . Abiraterone and Increased Survival in Metastatic Prostate Cancer, authored by de Bono, JS et al, took second place, with 2045 total citations and 292.14 annual citations. Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy, authored by Scher, HI et al, ranked third with 1857 total citations and 309.5 annual citations.
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Remission And The Chance Of Recurrence
A remission is when cancer cannot be detected in the body and there are no symptoms. This may also be called having no evidence of disease or NED.
A remission can be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. Although there are treatments to help prevent a recurrence, such as hormonal therapy and radiation therapy, it is important to talk with your doctor about the possibility of the cancer returning. There are tools your doctor can use, called nomograms, to estimate someone’s risk of recurrence. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the cancer does return. Learn more about coping with the fear of recurrence.
In general, following surgery or radiation therapy, the PSA level in the blood usually drops. If the PSA level starts to rise again, it may be a sign that the cancer has come back. If the cancer returns after the original treatment, it is called recurrent cancer.
When this occurs, a new cycle of testing will begin again to learn as much as possible about the recurrence, including where the recurrence is located. The cancer may come back in the prostate , in the tissues or lymph nodes near the prostate , or in another part of the body, such as the bones, lungs, or liver . Sometimes the doctor cannot find a tumor even though the PSA level has increased. This is known as a PSA recurrence or biochemical recurrence.
Advanced Prostate Cancer Metastatic Castration
This course series Advanced Prostate Cancer gives clinicians a complete view on clinical aspects, diagnosis, and treatments of prostate cancer.
|Duration||Approx. 150 180 minutes|
This course series contains five courses, each of them addresses an important topic in diagnosis, treatment, and management of prostate cancer. Each course is accredited by the European Accreditation Council for Continuing Medical Education for 1 to 3 European CME credits . The five courses are:
Course 4: Non-Metastatic Castration-Resistant PCa Course 5: Metastatic Castration-Resistant PCa
This course Metastatic Castration-Resistant Prostate Cancer is the fifth part of the course series.
The development of this course has been supported by Jansen with a concession of an unrestricted educational grant.
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Contributions Of Funding Agencies
Scientific productivity is related to research and development expenditures.86,87,88 The distribution of the top 20 most productive funding agencies for MCRPC research is displayed in Table Table6.6. The National Institutes of Health topped the list with 809 funded articles and the highest h-index . The pharmaceutical company Johnson & Johnson ranked second with 166 funded articles. The Prostate Cancer Foundation ranked third with 161 funded articles. Pfizer and Astellas followed the Department of Defense , which funded 161 articles. The National Natural Science Foundation of China ranked 11th with 77 funded articles and an h-index of 15. Twelve of these 20 funding agencies were global pharmaceutical companies, and the remaining 8 were state-funded institutions or charitable foundations. The NIH was the world’s largest funder of biomedical research and invested approximately $30 billion per year in biomedical research. The PCF was the world’s leading philanthropic organization funding and accelerating PCa research, and it raised more than $765 million and funded more than 2000 research programs at nearly 210 cancer centers and universities. The NNSFC, the largest natural science foundation in China, invested nearly $1.1 billion in biomedical research in 2018. Compared with the NIH and PCF, the NNSFC needs to expend more efforts to not only increase research sponsorship funds but also improve the quality of academic outputs.
Metastatic Hormone Sensitive Prostate Cancer
This form of prostate cancer can be an initial diagnosis but more often refers to cases where surgeries or other initial treatments to remove tumors from the prostate havent succeeded in stopping its progression.
Notably, too, these cases are defined by metastasis, meaning it has started to spread to other structures in the body, such as bones or the lymph nodes. However, the development of castration resistance is part of the eventual and expected progression of the diseaseeven while on ADT.
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The Role Of A Multidisciplinary Care Team In Treatment
Keep in mind that the optimal treatment strategy for mCRPC is different for each person and that its a complicated disease to treat. Thats why its important to assemble a team of doctors and specialists to keep your treatment and you on track.
Your team should include an experienced urologist, advises Cookson, as well oncologists who are comfortable with the newer treatments and know how to use them.
A study published in July 2015 in the Journal of Urology agrees, finding that with so many new treatments coming on board, doctors have to juggle a lot of factors when figuring out your best next steps from what kind of symptoms you have to your personal preferences, as well as any other health conditions that may have to be taken into account when coming up with a treatment strategy.
Its also important for your care team to review the medicines youve already taken for prostate cancer, and plan the sequence of the medicines youll take next. Getting the order right is important because certain drugs can make subsequent treatments more, or less, effective.
Your care team should also watch you closely to determine whether you have any resistance to any medicines, so that they can make changes quickly if necessary.
Ideally, your care team should possess expertise in distinct domains of cancer care, such as imaging, chemotherapy, radiation, and surgery, according to a study published in the Annals of Oncology in August 2015.
Study Design And Participants
CheckMate 9KD is a non-randomized, open-label, multicohort, phase 2 trial of nivolumab combined with rucaparib , docetaxel , or enzalutamide for mCRPC. Methods for the overall study and specific to cohort B have previously been described. In brief, the CheckMate 9KD study population comprises adult patients with histological confirmation of adenocarcinoma of the prostate with radiologic evidence of stage IV disease , ongoing androgen deprivation therapy or bilateral orchiectomy , and documented progressive disease per Prostate Cancer Clinical Trials Working Group 3 criteria. Eligible patients were also required to have an Eastern Cooperative Oncology Group performance status of 0 or 1 and sufficient tumor tissue obtained within 5 years before enrollment from a metastatic or primary tumor lesion not previously irradiated. Exclusion criteria included active brain metastases, conditions requiring systemic treatment with corticosteroids or other immunosuppressive medications within 14 days of start of study treatment, and prior therapy specifically targeting T-cell costimulation or immune checkpoint pathways.
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Abiraterone And Olaparib For Metastatic Castration
- Noel W. Clarke, M.B.B.S., Ch.M., F.R.C.S.1,
- Andrew J. Armstrong, Sc.M., M.D.2,
- Antoine Thiery-Vuillemin, M.D., Ph.D.3,
- Mototsugu Oya, M.D.4,
- Juliana de Menezes, M.D.8,
- Gustavo Girotto, M.D.9,
- Niven Mehra, M.D., Ph.D.11,
- Francis Parnis, F.R.A.C.P.12,
- Jae Y. Joung, M.D., Ph.D.15,
- Mikio Sugimoto, M.D., Ph.D.16,
- Juan A. Virizuela, M.D., Ph.D.17,
- Urban Emmenegger, M.D.18,
- Gary L. Buchschacher, Jr., M.D., Ph.D.20,
- Christian Poehlein, M.D.21,
- Elizabeth A. Harrington, Ph.D.22,
- Chintu Desai, Ph.D.23,
- Jinyu Kang, M.D.24, and
- Fred Saad, M.D., F.R.C.S.25
Quality Of Life With Mcrpc
According to a review published in the British Medical Journal in October 2016, you may not experience pain or other symptoms at this stage of cancer, or you may experience many. Its different for everyone. So along with treating the cancer itself, be sure to talk to your doctors about any symptoms and side effects youre experiencing in order so that the right ways to alleviate them can be found. You should also ask your care team about options for palliative care.
Because it can be very stressful to have advanced prostate cancer, and tough to talk about what it all means for your future, the ASCO urges men to have an open and honest conversation with their care team. Discuss what youre worried about, and whats important to you. There are many ways to look for and get emotional support.
Additional reporting by Andrea Peirce
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If Treatment Does Not Work
Recovery from cancer is not always possible. If the cancer cannot be cured or controlled, the disease may be called advanced or terminal.
This diagnosis is stressful, and for some people, advanced cancer may be difficult to discuss. However, it is important to have open and honest conversations with your health care team to express your feelings, preferences, and concerns. The health care team has special skills, experience, and knowledge to support patients and their families and is there to help. Making sure a person is physically comfortable, free from pain, and emotionally supported is extremely important.
People who have advanced cancer and who are expected to live less than 6 months may want to consider hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to talk with the health care team about hospice care options, which include hospice care at home, a special hospice center, or other health care locations. Nursing care and special equipment, including a hospital bed, can make staying at home a workable option for many families. Learn more about advanced cancer care planning.
After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.