{"id":47651,"date":"2022-08-25T13:02:03","date_gmt":"2022-08-25T11:02:03","guid":{"rendered":"https:\/\/pharma-trend.com\/en\/lynparza-olaparib-approved-in-japan-as-adjuvant-treatment-for-patients-with-brca-mutated-her2-negative-high-recurrent-risk-breast-cancer\/"},"modified":"2022-08-25T13:02:03","modified_gmt":"2022-08-25T11:02:03","slug":"lynparza-olaparib-approved-in-japan-as-adjuvant-treatment-for-patients-with-brca-mutated-her2-negative-high-recurrent-risk-breast-cancer","status":"publish","type":"post","link":"https:\/\/pharma-trend.com\/en\/lynparza-olaparib-approved-in-japan-as-adjuvant-treatment-for-patients-with-brca-mutated-her2-negative-high-recurrent-risk-breast-cancer\/","title":{"rendered":"LYNPARZA\u00ae (olaparib) Approved in Japan as Adjuvant Treatment for Patients With BRCA-Mutated, HER2-Negative High Recurrent Risk Breast Cancer"},"content":{"rendered":"
\n

\nFirst and only PARP inhibitor to improve invasive disease-free survival, the primary endpoint, and overall survival, a key secondary endpoint of the OlympiA trial, in these patients<\/b>\n<\/p>\n

RAHWAY, N.J.–(BUSINESS WIRE)–$MRK<\/a> #MRK<\/a>–AstraZeneca and Merck, known as MSD outside of the United States and Canada, today announced that LYNPARZA has been approved by the Japan Pharmaceuticals and Medical Devices Agency (PMDA) for the adjuvant treatment for patients with BRCA<\/i>-mutated (BRCA<\/i>m), human epidermal growth factor receptor 2 (HER2)-negative high recurrent risk breast cancer.\n<\/p>\n

<\/a><\/p>\n

\nThis approval was based on results from the Phase 3 OlympiA trial published in The New England Journal of Medicine <\/i>in June 2021. In the trial, LYNPARZA demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS), reducing the risk of invasive breast cancer recurrences, new cancers, or death by 42% (HR=0.58 [99.5% CI, 0.41-0.82]; p<0.0001) versus placebo.\n<\/p>\n

\nLYNPARZA also demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), reducing the risk of death by 32% (HR=0.68 [98.5% CI, 0.47-0.97]; p=0.009) versus placebo. The safety and tolerability profile of LYNPARZA in this trial was in line with that observed in prior clinical trials. The most common adverse reactions (ARs) \u226510% for LYNPARZA were nausea (57%), fatigue (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%) and stomatitis (10%). Approximately 10% of patients who received LYNPARZA discontinued treatment due to an AR. The most common Grade \u22653 ARs for LYNPARZA were anemia (9%), neutropenia (5%), leukopenia (3%) and fatigue (1.8%).\n<\/p>\n

\nBreast cancer is the most commonly diagnosed cancer worldwide, with an estimated 2.3 million patients diagnosed in 2020. In 2022, breast cancer is estimated to account for 95,000 new cases and over 15,000 deaths in Japan. <\/sup>Over 90% of all breast cancer patients in Japan are diagnosed with early breast cancer. BRCA<\/i> mutations are found in approximately 10% of HER2-negative patients.\n<\/p>\n

\nProfessor Andrew Tutt, global chair of the OlympiA trial and professor of oncology, The Institute of Cancer Research, London and King\u2019s College London, said, \u201cToday\u2019s approval marks a new era of care for patients in Japan. For patients with high-risk early-stage breast cancer, including those with germline BRCA<\/i> mutations, recurrence rates remain unacceptably high, with more than one in four of these patients seeing their cancer return following surgery and systemic treatment. Today\u2019s approval offers eligible patients in Japan an effective and targeted treatment that improves survival and helps to prevent cancer recurrence.\u201d\n<\/p>\n

\nDave Fredrickson, executive vice president, oncology business unit, AstraZeneca, said, \u201cToday\u2019s approval marks a significant leap forward for breast cancer patients in Japan, where it is the most commonly diagnosed cancer among women. Patients with BRCA <\/i>mutations have high rates of disease recurrence and lower survival, and LYNPARZA <\/i>has been shown to significantly reduce both the risk of recurrence and death. We hope this approval sets a new, much-needed standard of care for these early breast cancer patients in Japan.\u201d\n<\/p>\n

\nDr Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said, \u201cWith this approval, LYNPARZA becomes the first and only PARP inhibitor available for patients with BRCA<\/i>-mutated, HER2-negative early breast cancer in Japan. This further reinforces the critical need to conduct BRCA<\/i> testing at the point of diagnosis so that all eligible patients can be identified.\u201d\n<\/p>\n

\nIn March 2022, LYNPARZA <\/i>was approved in the U.S. for the adjuvant treatment of patients with germline BRCA<\/i>m (gBRCA<\/i>m), HER2-negative high-risk early breast cancer, followed by approval in the European Union (EU) in August 2022, based on results from the OlympiA trial. LYNPARZA is also approved in the U.S., EU, Japan and several other countries for the treatment of adult patients with gBRCA<\/i>m, HER2-negative, metastatic breast cancer previously treated with chemotherapy and, if hormone receptor-positive, endocrine therapy if appropriate based on results from the Phase 3 OlympiAD trial. In the EU, this indication also includes patients with locally advanced breast cancer.\n<\/p>\n

\nAbout OlympiA<\/b>\n<\/p>\n

\nOlympiA is a Phase 3, double-blind, parallel-group, placebo-controlled, international trial evaluating the efficacy and safety of LYNPARZA versus placebo as adjuvant treatment in patients with gBRCA<\/i>m, high-risk HER2-negative early breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. The primary endpoint of the trial is IDFS, defined as the time from randomization to the date of the first loco-regional or distant recurrence or new cancer or death from any cause. A key secondary efficacy outcome measure is OS.\n<\/p>\n

\nThe OlympiA trial is led by the Breast International Group in partnership with the Frontier Science & Technology Research Foundation, NRG Oncology, the U.S. National Cancer Institute, AstraZeneca and Merck. The trial is sponsored by NRG Oncology in the U.S. and by AstraZeneca outside of the U.S.\n<\/p>\n

\nIMPORTANT SAFETY INFORMATION<\/b>\n<\/p>\n

\nCONTRAINDICATIONS<\/b>\n<\/p>\n

\nThere are no contraindications for LYNPARZA.\n<\/p>\n

\nWARNINGS AND PRECAUTIONS<\/b>\n<\/p>\n

\nMyelodysplastic Syndrome\/Acute Myeloid Leukemia (MDS\/AML): <\/b>Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS\/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and\/or other DNA-damaging agents, including radiotherapy.\n<\/p>\n

\nDo not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (\u2264Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.\n<\/p>\n

\nIf the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS\/AML is confirmed.\n<\/p>\n

\nPneumonitis: <\/b>Occurred in 0.8% of patients exposed to LYNPARZA monotherapy, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.\n<\/p>\n

\nEmbryo-Fetal Toxicity: <\/b>Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.\n<\/p>\n

\nFemales<\/i>\n<\/p>\n

\nAdvise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.\n<\/p>\n

\nMales<\/i>\n<\/p>\n

\nAdvise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.\n<\/p>\n

\nVenous Thromboembolic Events:<\/b> Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.\n<\/p>\n

\nADVERSE REACTIONS\u2014First-Line Maintenance BRCA<\/i>m Advanced Ovarian Cancer<\/b>\n<\/p>\n

\nMost common adverse reactions (Grades 1-4) in \u226510% of patients who received LYNPARZA in the first-line maintenance setting<\/b> for SOLO-1 <\/b>were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection\/influenza\/nasopharyngitis\/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).\n<\/p>\n

\nMost common laboratory abnormalities (Grades 1-4) in \u226525% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1<\/b> were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).\n<\/p>\n

\nADVERSE REACTIONS\u2014First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab<\/b>\n<\/p>\n

\nMost common adverse reactions (Grades 1-4) in \u226510% of patients treated with LYNPARZA\/bevacizumab compared to a \u22655% frequency for placebo\/bevacizumab in the first-line maintenance setting<\/b> for PAOLA-1<\/b> were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (\u226510%) for patients receiving LYNPARZA\/bevacizumab irrespective of the frequency compared with the placebo\/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%).\n<\/p>\n

\nIn addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA\/bevacizumab (5%) than in those receiving placebo\/bevacizumab (1.9%).\n<\/p>\n

\nMost common laboratory abnormalities (Grades 1-4) in \u226525% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting<\/b> for PAOLA-1<\/b> were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%) and decrease in platelets (35%).\n<\/p>\n

\nADVERSE REACTIONS\u2014Maintenance Recurrent Ovarian Cancer<\/b>\n<\/p>\n

\nMost common adverse reactions (Grades 1-4) in \u226520% of patients who received LYNPARZA in the maintenance setting <\/b>for SOLO-2<\/b> were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis\/upper respiratory tract infection (URI)\/influenza (36%), diarrhea (33%), arthralgia\/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).\n<\/p>\n

\nStudy 19: <\/b>nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%) and dyspepsia (20%).\n<\/p>\n

\nMost common laboratory abnormalities (Grades 1-4) in \u226525% of patients who received LYNPARZA in the maintenance setting (SOLO-2\/Study 19<\/b>) were: increase in mean corpuscular volume (89%\/82%), decrease in hemoglobin (83%\/82%), decrease in leukocytes (69%\/58%), decrease in lymphocytes (67%\/52%), decrease in absolute neutrophil count (51%\/47%), increase in serum creatinine (44%\/45%), and decrease in platelets (42%\/36%).\n<\/p>\n

\nADVERSE REACTIONS\u2014Advanced gBRCA<\/i>m Ovarian Cancer After 3 or More Lines of Chemotherapy<\/b>\n<\/p>\n

\nMost common adverse reactions (Grades 1-4) in \u226520% of patients who received LYNPARZA for advanced gBRCA<\/i>m ovarian cancer after 3 or more lines of chemotherapy <\/b>(pooled from 6 studies) were: fatigue\/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis\/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia\/musculoskeletal pain (21%).\n<\/p>\n

\nMost common laboratory abnormalities (Grades 1-4) in \u226525% of patients who received LYNPARZA for advanced gBRCA<\/i>m ovarian cancer <\/b>(pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).\n<\/p>\n

\nADVERSE REACTIONS\u2014Adjuvant Treatment of gBRCA<\/i>m, HER2-Negative, High-Risk Early Breast Cancer<\/b>\n<\/p>\n

\nMost common adverse reactions (Grades 1-4) in \u226510% of patients who received LYNPARZA in the adjuvant setting<\/b> for OlympiA<\/b> were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).\n<\/p>\n

\nMost common laboratory abnormalities (Grades 1-4) in \u226525% of patients who received LYNPARZA in the adjuvant setting <\/b>for OlympiA<\/b> were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%).\n<\/p>\n

\nADVERSE REACTIONS\u2014gBRCA<\/i>m, HER2-Negative Metastatic Breast Cancer<\/b>\n<\/p>\n

\nMost common adverse reactions (Grades 1-4) in \u226520% of patients who received LYNPARZA in the metastatic setting<\/b> for OlympiAD<\/b> were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).\n<\/p>\n

\nMost common laboratory abnormalities (Grades 1-4) in ><\/span>25% of patients who received LYNPARZA in the metastatic setting<\/b> for OlympiAD <\/b>were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).\n<\/p>\n

\nADVERSE REACTIONS\u2014First-Line Maintenance gBRCA<\/i>m Metastatic Pancreatic Adenocarcinoma<\/b>\n<\/p>\n

\nMost common adverse reactions (Grades 1-4) in \u226510% of patients who received LYNPARZA in the first-line maintenance setting<\/b> for POLO <\/b>were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).\n<\/p>\n

\nMost common laboratory abnormalities (Grades 1-4) in \u226525% of patients who received LYNPARZA in the first-line maintenance setting<\/b> for POLO<\/b> were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).\n<\/p>\n

\nADVERSE REACTIONS\u2014HRR Gene-mutated Metastatic Castration Resistant Prostate Cancer<\/b>\n<\/p>\n

\nMost common adverse reactions (Grades 1-4) in \u226510% of patients who received LYNPARZA for PROfound<\/b> were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).\n<\/p>\n

\nMost common laboratory abnormalities (Grades 1-4) in \u226525% of patients who received LYNPARZA for PROfound<\/b> were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).\n<\/p>\n

\nDRUG INTERACTIONS<\/b>\n<\/p>\n

\nAnticancer Agents: <\/b>Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.\n<\/p>\n

\nCYP3A Inhibitors: <\/b>Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.\n<\/p>\n

\nCYP3A Inducers: <\/b>Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.\n<\/p>\n

\nUSE IN SPECIFIC POPULATIONS<\/b>\n<\/p>\n

\nLactation: <\/b>No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.\n<\/p>\n

\nPediatric Use: <\/b>The safety and efficacy of LYNPARZA have not been established in pediatric patients.\n<\/p>\n

\nHepatic Impairment: <\/b>No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).\n<\/p>\n

\nRenal Impairment: <\/b>No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL\/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL\/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr \u226430 mL\/min).\n<\/p>\n

\nINDICATIONS for LYNPARZA in the United States<\/b>\n<\/p>\n

\nLYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:\n<\/p>\n

\nFirst-Line Maintenance BRCA<\/i>m Advanced Ovarian Cancer<\/b>\n<\/p>\n

\nFor the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA<\/i>-mutated (gBRCA<\/i>m or sBRCA<\/i>m) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.\n<\/p>\n

\nFirst-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab<\/b>\n<\/p>\n

\nIn combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:\n<\/p>\n