Astrazeneca aims to redefine breast cancer care with new data across the treatment spectrum at sabcs 2022
Wilmington, del.--(business wire)--astrazeneca will present new data advancing its ambition to redefine care at the 2022 san antonio breast cancer symposium (sabcs), december 6-10, 2022. twelve astrazeneca medicines and potential new medicines will be featured in 55 presentations, including five oral presentations, showcasing the company’s growing leadership across different subtypes and stages of breast cancer. susan galbraith, executive vice president, oncology r&d, astrazeneca, said: “our data at sabcs are strong validation of our clinical strategy to provide next-generation treatment solutions for patients with nearly all major types of breast cancer. we are excited to share results from the pivotal capitello-291 trial, which will support the opportunity of our novel akt inhibitor capivasertib for patients with hr-positive disease. we also look forward to presenting defining data from the serena-2 phase ii trial that will demonstrate the potential of our next-generation serd camizestrant to improve upon currently available endocrine therapies for patients with er-driven disease.” dave fredrickson, executive vice president, oncology business unit, astrazeneca, said: “as we close another year of breakthroughs in breast cancer, our presence at sabcs will showcase the opportunity for our portfolio to shape clinical practice and redefine care across subtypes and stages of this disease. compelling results for potential new medicines capivasertib and camizestrant as well as new data from antibody drug conjugates enhertu® (fam-trastuzumab deruxtecan-nxki) and datopotamab deruxtecan will underscore our focus on addressing the greatest unmet needs and delivering personalized treatment for more patients with breast cancer.” aiming to set new standards of care across her2-positive metastatic breast cancer two late-breaking presentations from the destiny-breast clinical program will highlight the efficacy of enhertu treatment in patients with her2-positive metastatic breast cancer across lines of therapy. updated results from the destiny-breast03 phase iii trial of enhertu versus trastuzumab emtansine (t-dm1) in patients with her2-positive breast cancer previously treated with trastuzumab and a taxane will be presented, including updated progression-free survival (pfs) data and overall survival (os) results. in addition, primary results from the destiny-breast02 phase iii trial will be presented, further demonstrating the clinical benefit of enhertu compared to conventional chemotherapy-based regimens in patients with her2-positive metastatic breast cancer previously treated with t-dm1. data will also be presented from the roset-bm retrospective study and debbrah phase ii trial further confirming enhertu activity in patients with her2-positive or her2-low metastatic breast cancer with active or stable brain metastases. reshaping treatment expectations in hr-positive advanced breast cancer a late-breaking presentation will illustrate the company’s focus on addressing endocrine resistance in advanced hr-positive breast cancer. detailed data will be shared from the capitello-291 phase iii trial of the akt inhibitor capivasertib in combination with faslodex® (fulvestrant) versus faslodex alone in endocrine-resistant, hr-positive, her2-low or negative advanced breast cancer. capitello-291 recently met both primary endpoints, demonstrating improvement in pfs in the overall patient population and in a prespecified biomarker subgroup of patients whose tumors had qualifying alterations in the pik3ca, akt1 or pten genes. several presentations will establish the clinical potential of the next-generation oral selective estrogen receptor degrader (serd) camizestrant as a monotherapy or in combination for patients with estrogen receptor positive (er-positive) advanced breast cancer. a late-breaking presentation will highlight detailed results from the positive serena-2 phase ii trial of camizestrant versus faslodex in advanced er-positive breast cancer. analyses from further cohorts of the serena-1 phase i trial of advanced er-positive breast cancer will also be presented, which will show the potential to combine camizestrant with abemaciclib, a cdk4/6 inhibitor. a spotlight poster will feature data showing promising preclinical activity with camizestrant in er-positive breast cancer when used in double and triple combinations with cdk4/6, mtor, akt or pi3k inhibitors, in esr1 wild-type and mutated models. additionally, several presentations will showcase astrazeneca’s commitment to transforming the treatment landscape for hr-positive breast cancer with antibody drug conjugates (adcs) and by identifying new tumor subtypes that may respond to targeted therapies. a poster presentation of results from the tropion-pantumor01 phase i trial will characterize the safety and encouraging clinical activity of datopotamab deruxtecan in patients with heavily pre-treated hr-positive, her2-negative inoperable or metastatic breast cancer. datopotamab deruxtecan is also being tested in these patients in earlier lines of treatment in the randomized tropion-breast01 phase iii trial. multiple poster presentations will share results for potential diagnostic tools to better identify and optimize treatment for patients across the spectrum of her2 expression, including those with her2-low tumors who may benefit from treatment with enhertu. data from various subgroup analyses from the destiny-breast04 phase iii trial will reinforce the clinical meaningfulness of her2-low as an actionable patient segment in patients with metastatic breast cancer. redefining care for triple-negative breast cancer (tnbc) two spotlight poster discussions will share results from the begonia phase ib/ii trial testing imfinzi® (durvalumab) combinations in advanced or metastatic tnbc, showing the potential to drive improved outcomes with the addition of adcs. additionally, updated results from the tropion-pantumor01 phase i trial of datopotamab deruxtecan monotherapy will show encouraging and durable anti-tumor activity, and a manageable safety profile in heavily pre-treated patients with metastatic tnbc. the tropion-breast02 phase iii trial is evaluating datopotamab deruxtecan as 1st-line therapy for patients with metastatic tnbc. enhertu and datopotamab deruxtecan are developed and commercialized in collaboration with daiichi sankyo worldwide, except in japan where daiichi sankyo maintains exclusive rights. key astrazeneca presentations during sabcs 2022 lead author abstract title presentation details her2-positive breast cancer krop, i trastuzumab deruxtecan vs physician’s choice in patients with her2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized phase 3 study destiny-breast02 presentation #gs2-01 oral presentation – general session 2 december 7, 2022 9:00 – 9:15 am ct 15:00 – 15:15 gmt hurvitz, sa trastuzumab deruxtecan versus trastuzumab emtansine in patients with her2-positive metastatic breast cancer: updated survival results of the randomized, phase 3 study destiny-breast03 presentation #gs2-02 oral presentation – general session 2 december 7, 2022 9:15 – 9:30 am ct 15:15 – 15:30 gmt takashi, y trastuzumab deruxtecan for the treatment of patients with her2-positive breast cancer with brain and/or leptomeningeal metastases: a multicenter retrospective study (roset-bm study) presentation #pd7-01 spotlight poster discussion 7 december 7, 2022 17:00 ct 23:00 gmt hamilton, ep dose-expansion study of trastuzumab deruxtecan as monotherapy or combined with pertuzumab in patients with metastatic human epidermal growth factor receptor 2-positive (her2+) breast cancer in destiny-breast07 (db-07) presentation #pd18-11 spotlight poster discussion 18 december 9, 2022 07:00 ct 13:00 gmt varghese, d a real-world evidence study of treatment patterns in patients with her2-positive metastatic breast cancer who have received at least 2-lines of therapy presentation #p1-11-19 poster session 1 december 6, 2022 17:00 ct 23:00 gmt lam, c treatment patterns and outcomes among patients with her2-postive metastatic breast cancer in the united states presentation #p4-03-34 poster session 4 december 8, 2022 07:00 ct 13:00 gmt henderson, m adverse events (aes) in phase iii clinical trials of patients with human epidermal growth factor receptor-2 positive (her2+) breast cancer (bc): a meta-analysis presentation #p4-07-53 poster session 4 8 december 2022 07:00 ct 13:00 gmt lin, nu open-label, phase 3b/4 study of trastuzumab deruxtecan (t-dxd) in patients with or without baseline brain metastasis with advanced/metastatic human epidermal growth factor receptor 2–positive breast cancer: destiny-breast12 presentation #ot2-16-02 ongoing trials poster session 2 december 7, 2022 17:00 ct 23:00 gmt her2-low breast cancer prat, a determination of her2-low status in tumors of patients with unresectable and/or metastatic breast cancer in destiny-breast04 presentation #her2-18 her2 low: a separate entity special poster session december 7, 2022 09:45 – 11:00 ct 15:45 – 17:00 gmt viale, g retrospective study to estimate the prevalence and describe the clinicopathological characteristics, treatment patterns, and outcomes of her2-low breast cancer presentation #her2-15 her2 low: a separate entity special poster session december 7, 2022 09:45 – 11:00 ct 15:45 – 17:00 gmt rÜschoff, j proficiency assessment of her2-low breast cancer scoring with the ventana pathway 4b5 and dako herceptest her2 assays and the impact of pathologist training presentation #her2-13 her2 low: a separate entity special poster session december 7, 2022 09:45 – 11:00 ct 15:45 – 17:00 gmt schmid, p trastuzumab deruxtecan (t-dxd) + durvalumab (d) as first-line (1l) treatment for unresectable locally advanced/metastatic hormone receptor-negative (hr−), her2-low breast cancer: updated results from begonia, a phase 1b/2 study presentation #pd11-08 spotlight poster discussion 11 december 8, 2022 07:00 ct 13:00 gmt pÉrez-garcÍa, jm trastuzumab deruxtecan in patients with unstable central nervous system involvement from her2-low advanced breast cancer: the debbrah trial presentation #pd7-02 spotlight poster discussion 7 december 7, 2022 17:00 ct 23:00 gmt harbeck, n trastuzumab deruxtecan vs treatment of physician’s choice in patients with her2-low unresectable and/or metastatic breast cancer: subgroup analyses from destiny-breast04 presentation #p1-11-01 poster session 1 december 6, 2022 17:00 ct 23:00 gmt spitzmÜller, a computational pathology based her2 expression quantification in her2-low breast cancer presentation #p6-04-03 poster session 6 december 9, 2022 07:00 ct 13:00 gmt tsirka, a high intra- and inter-block concordance of her2 immunohistochemistry (ihc) scores across breast cancer samples and impact of decalcification procedures presentation #p6-04-17 poster session 6 december 9, 2022 07:00 ct 13:00 gmt globerson, y a fully automatic artificial intelligence system for accurate and reproducible her2 ihc scoring in breast cancer presentation #p6-04-05 poster session 6 december 9, 2022 07:00 ct 13:00 gmt kapil, a art: automated region segmentation of tumor on her2-stained breast cancer tissue presentation #p6-04-16 poster session 6 december 9, 2022 07:00 ct 13:00 gmt hr-positive breast cancer hurvitz, sa trio-us b-12 talent: neoadjuvant trastuzumab deruxtecan with or without anastrozole for her2-low, hr+ early stage breast cancer presentation #gs2-03 oral presentation – general session 2 december 7, 2022 09:30 – 09:45 ct 15:30 – 15:45 gmt oliveira, m camizestrant, a next generation oral serd vs fulvestrant in post-menopausal women with advanced er-positive her2-negative breast cancer: results of the randomized, multi-dose phase 2 serena-2 trial presentation #gs3-02 oral presentation – general session 3 december 8, 2022 08:45 – 09:00 ct 14:45 – 15:00 gmt turner, nc capivasertib and fulvestrant for patients with aromatase inhibitor-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: results from the phase iii capitello-291 trial presentation #gs3-04 oral presentation – general session 3 december 8, 2022 09:15 – 09:30 ct 15:15 – 15:30 gmt meric-bernstam, f phase 1 tropion-pantumor01 study evaluating datopotamab deruxtecan (dato-dxd) in unresectable or metastatic hormone receptor–positive/her2–negative breast cancer (bc) presentation #pd13-08 spotlight poster discussion 13 december 8, 2022 17:00 ct 23:00 gmt carnevalli, l combination of the next generation oral serd camizestrant (azd9833) with cdk4/6 and mtor/akt inhibitors delivers robust efficacy in a broad range of er+ breast tumors presentation #pd10-04 spotlight poster discussion 10 december 8, 2022 07:00 ct 13:00 gmt morrow, c the next generation oral selective estrogen receptor degrader (serd) camizestrant (azd9833) is active against wild type and mutant estrogen receptor Α presentation #p3-07-13 poster session 3 december 7, 2022 17:00 ct 23:00 gmt bardia, a datopotamab deruxtecan (dato-dxd), a trop2 antibody-drug conjugate,vs investigators’ choice of chemotherapy in previously-treated, inoperable or metastatic hr+/her2–breast cancer: tropion-breast01 presentation #ot1-03-04 ongoing trials poster session 1 december 6, 2022 17:00 ct 23:00 gmt turner, nc serena-1: updated analyses from a phase 1 study of the next generation oral selective estrogen receptor degrader camizestrant (azd9833) combined with abemaciclib, in women with er-positive, her2-negative advanced breast cancer presentation #ot2-02-01 ongoing trials poster session 2 december 7, 2022 17:00 ct 23:00 gmt tnbc and brca-mutated breast cancer schmid, p datopotamab deruxtecan (dato-dxd) + durvalumab (d) as first-line (1l) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mtnbc): updated results from begonia, a phase 1b/2 study presentation #pd11-09 spotlight poster discussion 11 december 8, 2022 07:00 ct 13:00 gmt bardia, a datopotamab deruxtecan (dato-dxd) in advanced triple-negative breast cancer (tnbc): updated results from the phase 1 tropion-pantumor01 study presentation #p6-10-03 poster session 6 december 9, 2022 07:00 ct 13:00 gmt copson, er expert consensus on the definition of high risk of recurrence in her2-negative ebc: a modified delphi panel presentation #p3-05-39 poster session 3 december 7, 2022 17:00 ct 23:00 gmt dent, r tropion-breast02: phase 3, open-label, randomized study of first-line datopotamab deruxtecan versus chemotherapy in patients with locally recurrent inoperable or metastatic tnbc who are not candidates for anti-pd-(l)1 therapy presentation #ot1-03-05 ongoing trials poster session 1 december 6, 2022 17:00 ct 23:00 gmt balmaÑa, j olympian: a phase 2, multicenter, open-label study to assess the efficacy and safety of neoadjuvant olaparib monotherapy and olaparib plus durvalumab in patients with brca mutations and early-stage her2-negative breast cancer presentation #ot2-18-02 ongoing trials poster session 2 december 7, 2022 17:00 ct 23:00 gmt u.s. important safety information for enhertu indications enhertu is a her2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: unresectable or metastatic her2-positive breast cancer who have received a prior anti-her2-based regimen either: in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy unresectable or metastatic her2-low (ihc 1+ or ihc 2+/ish-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy unresectable or metastatic non-small cell lung cancer (nsclc) whose tumors have activating her2 (erbb2) mutations, as detected by an fda-approved test, and who have received a prior systemic therapy this indication is approved under accelerated approval based on objective response rate and duration of response. continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. locally advanced or metastatic her2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen warning: interstitial lung disease and embryo-fetal toxicity interstitial lung disease (ild) and pneumonitis, including fatal cases, have been reported with enhertu. monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. permanently discontinue enhertu in all patients with grade 2 or higher ild/pneumonitis. advise patients of the risk and to immediately report symptoms. exposure to enhertu during pregnancy can cause embryo-fetal harm. advise patients of these risks and the need for effective contraception. contraindications none. warnings and precautions interstitial lung disease / pneumonitis severe, life-threatening, or fatal interstitial lung disease (ild), including pneumonitis, can occur in patients treated with enhertu. advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. monitor patients for signs and symptoms of ild. promptly investigate evidence of ild. evaluate patients with suspected ild by radiographic imaging. consider consultation with a pulmonologist. for asymptomatic ild/pneumonitis (grade 1), interrupt enhertu until resolved to grade 0, then if resolved in ≤28 days from date of onset, maintain dose. if resolved in >28 days from date of onset, reduce dose one level. consider corticosteroid treatment as soon as ild/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). for symptomatic ild/pneumonitis (grade 2 or greater), permanently discontinue enhertu. promptly initiate systemic corticosteroid treatment as soon as ild/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. metastatic breast cancer in clinical studies, of the 491 patients with unresectable or metastatic her2-positive breast cancer treated with enhertu 5.4 mg/kg, ild occurred in 13% of patients. fatal outcomes due to ild and/or pneumonitis occurred in 1.4% of patients treated with enhertu. median time to first onset was 5.5 months (range: 1.1 to 20.8). locally advanced or metastatic gastric cancer in destiny-gastric01, of the 125 patients with locally advanced or metastatic her2‑positive gastric or gej adenocarcinoma treated with enhertu 6.4 mg/kg, ild occurred in 10% of patients. median time to first onset was 2.8 months (range: 1.2 to 21.0). neutropenia severe neutropenia, including febrile neutropenia, can occur in patients treated with enhertu. monitor complete blood counts prior to initiation of enhertu and prior to each dose, and as clinically indicated. for grade 3 neutropenia (absolute neutrophil count [anc] 38.3ºc or a sustained temperature of ≥38ºc for more than 1 hour), interrupt enhertu until resolved. reduce dose by one level. metastatic breast cancer in clinical studies, of the 491 patients with unresectable or metastatic her2-positive breast cancer who received enhertu 5.4 mg/kg, a decrease in neutrophil count was reported in 68% of patients. eighteen percent had grade 3 or 4 decrease in neutrophil count. median time to first onset of decreased neutrophil count was 22 days (range: 6 to 664). febrile neutropenia was reported in 1.2% of patients. locally advanced or metastatic gastric cancer in destiny-gastric01, of the 125 patients with locally advanced or metastatic her2‑positive gastric or gej adenocarcinoma treated with enhertu 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. fifty-one percent had grade 3 or 4 decreased neutrophil count. median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). febrile neutropenia was reported in 4.8% of patients. left ventricular dysfunction patients treated with enhertu may be at increased risk of developing left ventricular dysfunction. left ventricular ejection fraction (lvef) decrease has been observed with anti-her2 therapies, including enhertu. assess lvef prior to initiation of enhertu and at regular intervals during treatment as clinically indicated. manage lvef decrease through treatment interruption. when lvef is >45% and absolute decrease from baseline is 10-20%, continue treatment with enhertu. when lvef is 40-45% and absolute decrease from baseline is 20%, interrupt enhertu and repeat lvef assessment within 3 weeks. if lvef of 20% is confirmed, permanently discontinue enhertu. permanently discontinue enhertu in patients with symptomatic congestive heart failure. treatment with enhertu has not been studied in patients with a history of clinically significant cardiac disease or lvef 1% of patients who received enhertu were vomiting, interstitial lung disease, pneumonia, pyrexia, and urinary tract infection. fatalities due to adverse reactions occurred in 0.8% of patients including covid-19 and sudden death (one patient each). enhertu was permanently discontinued in 14% of patients, of which ild/pneumonitis accounted for 8%. dose interruptions due to adverse reactions occurred in 44% of patients treated with enhertu. the most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ild/pneumonitis. dose reductions occurred in 21% of patients treated with enhertu. the most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue. the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), hypokalemia (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), respiratory infection (22%), headache (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%). locally advanced or metastatic gastric cancer the safety of enhertu was evaluated in 187 patients with locally advanced or metastatic her2positive gastric or gej adenocarcinoma in destinygastric01. patients intravenously received at least one dose of either enhertu (n=125) 6.4 mg/kg once every three weeks or either irinotecan (n=55) 150 mg/m2 biweekly or paclitaxel (n=7) 80 mg/m2 weekly for 3 weeks. the median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the enhertu group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group. serious adverse reactions occurred in 44% of patients receiving enhertu 6.4 mg/kg. serious adverse reactions in >2% of patients who received enhertu were decreased appetite, ild, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%). enhertu was permanently discontinued in 15% of patients, of which ild accounted for 6%. dose interruptions due to adverse reactions occurred in 62% of patients treated with enhertu. the most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ild, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. dose reductions occurred in 32% of patients treated with enhertu. the most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia. the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%). use in specific populations pregnancy: enhertu can cause fetal harm when administered to a pregnant woman. advise patients of the potential risks to a fetus. there are clinical considerations if enhertu is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of enhertu. lactation: there are no data regarding the presence of enhertu in human milk, the effects on the breastfed child, or the effects on milk production. because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with enhertu and for 7 months after the last dose. females and males of reproductive potential: pregnancy testing: verify pregnancy status of females of reproductive potential prior to initiation of enhertu. contraception: females: enhertu can cause fetal harm when administered to a pregnant woman. advise females of reproductive potential to use effective contraception during treatment with enhertu and for at least 7 months following the last dose. males: advise male patients with female partners of reproductive potential to use effective contraception during treatment with enhertu and for at least 4 months following the last dose. infertility: enhertu may impair male reproductive function and fertility. pediatric use: safety and effectiveness of enhertu have not been established in pediatric patients. geriatric use: of the 491 patients with her2-positive breast cancer treated with enhertu 5.4 mg/kg, 22% were ≥65 years and 4% were ≥75 years. no overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. there was a higher incidence of grade 3-4 adverse reactions observed in patients aged ≥65 years (60%) as compared to younger patients (49%). of the 125 patients with locally advanced or metastatic her2‑positive gastric or gej adenocarcinoma treated with enhertu 6.4 mg/kg in destiny-gastric01, 56% were ≥65 years and 14% were ≥75 years. no overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. renal impairment: a higher incidence of grade 1 and 2 ild/pneumonitis has been observed in patients with moderate renal impairment. monitor patients with moderate or severe renal impairment. hepatic impairment: in patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor. to report suspected adverse reactions, contact daiichi sankyo, inc. at 1-877-437-7763 or fda at 1-800-fda-1088 or fda.gov/medwatch. please see accompanying full prescribing information, including boxed warnings, and medication guide. important safety information about faslodex® (fulvestrant) injection contraindications faslodex is contraindicated in patients with known hypersensitivity to the drug or to any of its components. hypersensitivity reactions, including urticaria and angioedema, have been reported in association with faslodex warnings and precautions risk of bleeding because faslodex is administered intramuscularly, it should be used with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use hepatic impairment faslodex is metabolized primarily in the liver. a 250 mg dose is recommended in patients with moderate hepatic impairment (child-pugh class b). faslodex has not been evaluated in patients with severe hepatic impairment (child-pugh class c) injection site reaction use caution while administering faslodex at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve. injection site-related events, including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy, have been reported with faslodex injection embryo-fetal toxicity and lactation pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating faslodex advise pregnant women of the potential risk to a fetus. advise women of reproductive potential to use effective contraception during faslodex treatment and for 1 year after the last dose. advise lactating women not to breastfeed during treatment with faslodex and for 1 year after the final dose because of the potential risk to the infant immunoassay measurement of serum estradiol due to structural similarity of fulvestrant and estradiol, faslodex can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels adverse reactions monotherapy the most common adverse reactions occurring in ≥5% of patients receiving faslodex 500 mg were injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, myalgia, vomiting, anorexia, diarrhea, asthenia, musculoskeletal pain, cough, dyspnea, and constipation increased hepatic enzymes (alt, ast, alp) occurred in >15% of faslodex patients and were not dose-dependent combination therapy – faslodex plus ribociclib the most frequently reported (≥5%) grade 3 or 4 adverse reactions in patients receiving faslodex plus ribociclib in descending frequency were neutropenia, leukopenia, infections, and abnormal liver function tests the most common adverse reactions (≥20%) of any grade reported in patients receiving faslodex 500 mg plus ribociclib 600 mg/day were neutropenia, infections, leukopenia, cough, nausea, diarrhea, vomiting, constipation, pruritus, and rash additional adverse reactions in patients receiving faslodex plus ribociclib included asthenia, dyspepsia, thrombocytopenia, dry skin, dysgeusia, electrocardiogram qt prolonged, dry mouth, vertigo, dry eye, lacrimation increased, erythema, hypocalcemia, blood bilirubin increased, and syncope combination therapy—faslodex plus palbociclib the most frequently reported grade ≥3 adverse reactions in patients receiving faslodex plus palbociclib in descending frequency were neutropenia and leukopenia adverse reactions (≥10%) of any grade reported in patients receiving faslodex 500 mg plus palbociclib 125 mg/day by descending frequency were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, diarrhea, thrombocytopenia, vomiting, alopecia, rash, decreased appetite, and pyrexia additional adverse reactions occurring at an overall incidence of 1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). fatal adverse reactions occurred in 8% of patients who received imjudo in combination with durvalumab, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients the safety and effectiveness of imfinzi and imjudo have not been established in pediatric patients. indications: imfinzi is indicated for the treatment of adult patients with unresectable stage iii non-small cell lung cancer (nsclc) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. imfinzi, in combination with imjudo and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic nsclc with no sensitizing epidermal growth factor receptor (egfr) mutations or anaplastic lymphoma kinase (alk) genomic tumor aberrations. imfinzi, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (es-sclc). imfinzi, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (btc). imfinzi in combination with imjudo is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uhcc). notes astrazeneca in breast cancer driven by a growing understanding of breast cancer biology, astrazeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. astrazeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment. with enhertu, a her2-directed adc, astrazeneca and daiichi sankyo are aiming to improve outcomes in previously treated her2-positive and her2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings. in hr-positive breast cancer, astrazeneca continues to improve outcomes with foundational medicines faslodex® (fulvestrant) and zoladex and aims to reshape the hr-positive space with ngserd and potential new medicine camizestrant as well as a potential first-in-class akt kinase inhibitor, capivasertib. astrazeneca is also collaborating with daiichi sankyo to explore the potential of trop2-directed adc, datopotamab deruxtecan, in this setting. parp inhibitor lynparza® (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited brca mutation. astrazeneca with merck & co., inc., kenilworth, nj, us, known as msd outside the us and canada continue to research lynparza in metastatic breast cancer patients with an inherited brca mutation and are exploring new opportunities to treat these patients earlier in their disease. to bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, astrazeneca is testing immunotherapy imfinzi (durvalumab) in combination with other oncology medicines, including lynparza and enhertu, evaluating the potential of capivasertib in combination with chemotherapy, and datopotamab deruxtecan. astrazeneca in oncology astrazeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. the company’s focus is on some of the most challenging cancers. it is through persistent innovation that astrazeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. astrazeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. about astrazeneca astrazeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in oncology, rare diseases, and biopharmaceuticals, including cardiovascular, renal & metabolism, and respiratory & immunology. based in cambridge, uk, astrazeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. please visit www.astrazeneca-us.com and follow the company on twitter @astrazenecaus. us-71247 last updated 11/22
