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INDIANAPOLIS, May 13, 2020 /PRNewswire/ -- Data from 23 studies across Eli Lilly and Company's (NYSE: LLY) oncology product portfolio will be presented at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO), held virtually, May 29-31, 2020. The data, which include an updated analysis of Lilly's newest precision medicine Retevmo™ (selpercatinib), underscore Lilly Oncology's dedication to developing and delivering innovative new medicines that will make a meaningful difference to people living with cancer.
"We're excited to present data at this year's ASCO that highlight our commitment to developing new targeted treatments for people living with cancer. We are especially looking forward to sharing data from our LIBRETTO-001 trial examining Retevmo, which recently received FDA approval for the treatment of certain cancers that develop due to alterations of the RET gene," said Maura Dickler, M.D., vice president, late phase development, Lilly Oncology. "Even though we're not gathering in person this year, we remain committed to gathering virtually with physicians to share important new data so they may choose the best therapy for their patients who have difficult-to-treat, advanced stage cancers."
Latest Study Results for Retevmo Last week, Lilly's first-in-class precision medicine, Retevmo—a selective oral RET kinase inhibitor—received approval from the U.S. Food and Drug Administration (FDA) for the treatment of metastatic RET fusion-positive non-small cell lung cancer (NSCLC), advanced or metastatic RET-mutant medullary thyroid cancer (MTC) and advanced or metastatic RET fusion-positive thyroid cancer.
During ASCO, Lilly will share updated detailed results from the Phase 1/2 LIBRETTO-001 registrational trial of Retevmo. The updated analysis will be presented on both the NSCLC and thyroid cohorts, as well as on activity in difficult-to-treat brain metastases in patients with NSCLC. LIBRETTO-001 is the largest clinical trial in RET-altered cancers and builds on earlier research that has shown that Retevmo is a selective and potent inhibitor of RET. The most common adverse reactions, including laboratory abnormalities, (≥ 25%) were increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema, decreased platelets, increased total cholesterol, rash, decreased sodium, and constipation. In addition, the most frequent serious adverse reaction (in ≥ 2% of patients) was pneumonia.
RET fusions have been identified in approximately two percent of NSCLC and 10-20 percent of papillary, Hurthle cell, anaplastic and poorly differentiated thyroid cancers. Activating RET point mutations account for approximately 60 percent of sporadic MTC and approximately 90 percent of germline MTC.
Lilly's Commitment to Advanced Breast Cancer PatientsNew data for Verzenio® (abemaciclib) include research on acquired genomic alterations in circulating tumor DNA (ctDNA)—an area of particular interest as oncologists seek to understand how to individualize treatment for people living with HR+, HER2- advanced breast cancer. Lilly will also present further overall survival (OS) exploratory subgroup data on women with advanced breast cancer receiving Verzenio plus fulvestrant in the first- and second-line settings in the MONARCH 2 trial.
CYRAMZA® and ALIMTA® Lung Cancer Data Highlights Lilly will present new data from the positive Phase 3 RELAY study evaluating CYRAMZA (ramucirumab) plus erlotinib—specifically a biomarker analysis using circulating tumor DNA (ctDNA) in Japanese patients with untreated metastatic EGFR-mutated NSCLC, as well as an exploratory analysis of CYRAMZA plus gefitinib in patients with EGFR-mutated NSCLC. Last year, Lilly made a U.S. regulatory submission based on the RELAY intent-to-treat (ITT) patient population and FDA action is expected in the first half of 2020. In addition to a recent approval for CYRAMZA in the European Union based on the RELAY ITT results, Lilly has made a submission in Japan with regulatory action expected by the end of 2020.
Additionally, a final analysis of OS data from the KEYNOTE-189 trial, which enrolled patients with NSCLC regardless of PD-L1 expression and examined the ALIMTA (pemetrexed)-KEYTRUDA® (pembrolizumab)-platinum chemotherapy combination in the first-line setting, will be presented. The KEYNOTE-189 trial was conducted by Merck (known as MSD outside the U.S. and Canada) in collaboration with Lilly.
A list of the data presentations, along with the viewing details are highlighted below.
Retevmo (selpercatinib)
Abstract 3584: Selpercatinib (LOXO-292) in patients with RET-fusion+ non-small cell lung cancer (Koichi Goto)Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Poster: 314
Abstract 9516: Intracranial activity of selpercatinib (LOXO-292) in RET fusion-positive non-small cell lung cancer (NSCLC) patients on the LIBRETTO-001 trial (Vivek Subbiah)Session: Lung Cancer—Non-Small Cell MetastaticPoster: 282
Abstract 3594: Selpercatinib (LOXO-292) in patients with RET-mutant medullary thyroid cancer (Manisha H. Shah)Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Poster: 324
Abstract e21693: Clinical outcomes between patients with and without RET fusions in advanced/metastatic non-small cell lung cancer in the United States (Anthony Sireci)Publication Only
Verzenio (abemaciclib)
Abstract 1061: MONARCH 2: subgroup analysis of patients receiving abemaciclib + fulvestrant as first- and second-line therapy for HR+, HER2- advanced breast cancer (Patrick Neven)Session: Breast Cancer—MetastaticPoster: 146
Abstract 3519: Acquired genomic alterations in circulating tumor DNA from patients receiving abemaciclib alone or in combination with endocrine therapy (Matthew P. Goetz)Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Poster: 249
Abstract 9562: A phase Ib study of abemaciclib in combination with pembrolizumab for patients (pts) with stage IV Kirsten rat sarcoma mutant (KRAS-mut) or squamous non-small cell lung cancer (NSCLC) (NCT02779751): Interim results (Jean-Louis Pujol)Session: Lung Cancer—Non-Small Cell MetastaticPoster: 328
Abstract 1051: A phase Ib study of abemaciclib in combination with pembrolizumab for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer (MBC) (NCT02779751): Interim results (Hope S. Rugo)Session: Breast Cancer—MetastaticPoster: 136
Abstract TPS5591: CYCLONE 2: A phase II, randomized, placebo-controlled study of abiraterone acetate plus prednisone with or without abemaciclib in patients with metastatic castration-resistant prostate cancer (Matthew R. Smith)Session: Genitourinary Cancer—Prostate, Testicular, and PenilePoster: 172
Abstract e13083: Assessment for markers of poor prognosis in a real-world evidence study of treatment patterns in patients with HR+/HER2- locally advanced or metastatic breast cancer in Korea and Taiwan (Diego Novick)Publication Only
CYRAMZA (ramucirumab)
Abstract 9564: RELAY+: Exploratory study of ramucirumab plus gefitinib in untreated patients (pts) with epidermal growth factor receptor (EGFR)-mutated metastatic non-small cell lung cancer (NSCLC) (Makoto Nishio)Session: Lung Cancer—Non-Small Cell MetastaticPoster: 330
Abstract 9527: RELAY study of erlotinib (ERL) + ramucirumab (RAM) or placebo (PL) in EGFR-mutated metastatic non-small cell lung cancer (NSCLC): Biomarker analysis using circulating tumor DNA (ctDNA) in Japanese patients (pts) (Kazuto Nishio)Session: Lung Cancer—Non-Small Cell MetastaticPoster: 293
Abstract 4644: Ramucirumab in patients with advanced HCC and elevated alpha-fetoprotein (AFP): Outcomes by treatment-emergent ascites (Andrew X. Zhu)Session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and HepatobiliaryPoster: 252
Abstract 4543: Impact of frontline doublet versus triplet therapy on clinical outcomes: Exploratory analysis from the RAINBOW study (Samuel J. Klempner)Session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and HepatobiliaryPoster: 151
Abstract 3089: Immune profiling and clinical outcomes in patients treated with ramucirumab and pembrolizumab in phase I study JVDF (Roy S. Herbst)Session: Developmental Therapeutics—ImmunotherapyPoster: 153
ALIMTA (pemetrexed)
Abstract 9521: Evaluation of blood TMB (bTMB) in KEYNOTE-189: Pembrolizumab (pembro) plus chemotherapy (chemo) with pemetrexed and platinum versus placebo plus chemo as first-line therapy for metastatic nonsquamous NSCLC (Marina C. Garassino)Session: Lung Cancer—Non-Small Cell MetastaticPoster: 287
Abstract 9582: Final analysis of KEYNOTE-189: Pemetrexed-platinum chemotherapy (chemo) with or without pembrolizumab (pembro) in patients (pts) with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC) (Delvys Rodriguez-Abreu)Session: Lung Cancer—Non-Small Cell MetastaticPoster: 348
Other
Abstract e16001: Early carcinoembryonic antigen (CEA) dynamics to predict fruquintinib efficacy in FRESCO, a 3+ line metastatic colorectal carcinoma (mCRC) phase III trial (Yuxian Bai)Publication Only
Abstract 9563: Randomized phase II study of pembrolizumab (P) alone versus pegilodecakin (PEG) in combination with P as first-line (1L) therapy in patients (pts) with stage IV non-small cell lung cancer (NSCLC) with high PD-L1 expression (CYPRESS 1) (David R. Spigel)Session: Lung Cancer—Non-Small Cell MetastaticPoster: 329
Abstract e21744: Randomized phase II study of nivolumab (N) alone versus with pegilodecakin (PEG) in combination with N in patients (pts) with post-platinum immunotherapy-naive stage IV non-small cell lung cancer (NSCLC) and no or low PD-L1 expression (CYPRESS 2) (Robert M. Jotte)Publication Only
Abstract TPS10561: A phase I study of Aurora kinase A inhibitor LY3295668 erbumine as a single agent and in combination in patients with relapsed/refractory neuroblastoma (Steven G. DuBois)Session: Pediatric OncologyPoster: 448
Abstract 3588: Correlation between overall response rate and progression-free survival/overall survival in comparative trials involving targeted therapies in molecularly enriched populations (Benjamin J. Solomon)Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor BiologyPoster: 318
Abstract e19123: Impact of bolus versus continuous infusion of doxorubicin (DOX) on cardiotoxicity in patients with breast cancer (BC) and sarcomas: Analysis of real-world data (Lee D. Cranmer)Publication Only
Notes to Editors
About Retevmo™ (selpercatinib)Retevmo (selpercatinib, formerly known as LOXO-292) (pronounced reh-TEHV-moh) is a selective and potent RET kinase inhibitor. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. Retevmo is an oral prescription medicine, 120 mg or 160 mg dependent on weight (-/+ 50 kg), taken twice daily until disease progression or unacceptable toxicity.
About Verzenio® (abemaciclib)Verzenio (abemaciclib) is an inhibitor of cyclin-dependent kinases (CDK)4 & 6, which are activated by binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4 & 6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation.
In vitro, continuous exposure to Verzenio inhibited Rb phosphorylation and blocked progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in reduction of tumor size. Inhibiting CDK4 & 6 in healthy cells can result in side effects, some of which may be serious. Clinical evidence also suggests that Verzenio crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, concentrations of Verzenio and its active metabolites (M2 and M20) in cerebrospinal fluid are comparable to unbound plasma concentrations.
Verzenio is Lilly's first solid oral dosage form to be made using a faster, more efficient process known as continuous manufacturing. Continuous manufacturing is a new and advanced type of manufacturing within the pharmaceutical industry, and Lilly is one of the first companies to use this technology.
Verzenio is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer:
About CYRAMZA® (ramucirumab)In the U.S., CYRAMZA (ramucirumab) has five FDA approvals to treat four different types of cancers. CYRAMZA is being investigated in a broad global development program that has enrolled more than 15,000 patients across more than 100 trials worldwide. These include several studies investigating CYRAMZA in combination with other anti-cancer therapies for the treatment of multiple tumor types.
CYRAMZA is an antiangiogenic therapy. It is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that binds specifically to VEGFR-2, thereby blocking the binding of the receptor ligands (VEGF-A, VEGF-C, and VEGF-D) – which may slow tumor growth. CYRAMZA inhibited angiogenesis in an in vivo animal model.
U.S. INDICATIONS FOR CYRAMZA
Gastric Cancer CYRAMZA, as a single agent, or in combination with paclitaxel, is indicated for the treatment of patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
Non-Small Cell Lung CancerCYRAMZA, in combination with docetaxel, is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving CYRAMZA.
Colorectal Cancer CYRAMZA, in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
Hepatocellular CarcinomaCYRAMZA, as a single agent, is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have an alpha-fetoprotein (AFP) of ≥400 ng/mL and have been treated with sorafenib.
About ALIMTA® (pemetrexed for injection)ALIMTA is indicated in combination with pembrolizumab and platinum chemotherapy for the initial treatment of patients with metastatic nonsquamous non-small cell lung cancer, with no EGFR or ALK genomic tumor aberrations. For all FDA-approved indications for ALIMTA, please see full Prescribing Information.
IMPORTANT SAFETY INFORMATION FOR RETEVMO™ (selpercatinib)
Hepatotoxicity: Serious hepatic adverse reactions occurred in 2.6% of patients treated with Retevmo. Increased AST occurred in 51% of patients, including Grade 3 or 4 events in 8% and increased ALT occurred in 45% of patients, including Grade 3 or 4 events in 9%. The median time to first onset for increased AST was 4.1 weeks (range: 5 days to 2 years) and increased ALT was 4.1 weeks (range: 6 days to 1.5 years). Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue Retevmo based on the severity.
Hypertension occurred in 35% of patients, including Grade 3 hypertension in 17% and Grade 4 in one (0.1%) patient. Overall, 4.6% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent QT interval prolongation. An increase in QTcF interval to >500 ms was measured in 6% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 15% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure.
Assess QT interval, electrolytes and TSH at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity.
Serious, including fatal, hemorrhagic events can occur with Retevmo. Grade ≥ 3 hemorrhagic events occurred in 2.3% of patients treated with Retevmo including 3 (0.4%) patients with fatal hemorrhagic events, including one case each of cerebral hemorrhage, tracheostomy site hemorrhage, and hemoptysis. Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage.
Hypersensitivity occurred in 4.3% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.6%. The median time to onset was 1.7 weeks (range 6 days to 1.5 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg. Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity.
Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established.
Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause fetal harm when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for at least 1 week after the final dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the final dose.
Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-001, were hypertension (18%), prolonged QT interval (4%), diarrhea (3.4%), dyspnea (2.3%), fatigue (2%), abdominal pain (1.9%), hemorrhage (1.9%), headache (1.4%), rash (0.7%), constipation (0.6%), nausea (0.6%), vomiting (0.3%), and edema (0.3%).
Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-001, were dry mouth (39%), diarrhea (37%), hypertension (35%), fatigue (35%), edema (33%), rash (27%), constipation (25%), nausea (23%), abdominal pain (23%), headache (23%), cough (18%), prolonged QT interval (17%), dyspnea (16%), vomiting (15%), and hemorrhage (15%).
Laboratory abnormalities (all grades; Grade 3-4) ≥20% worsening from baseline in patients who received Retevmo in LIBRETTO-001, were AST increased (51%; 8%), ALT increased (45%; 9%), increased glucose (44%; 2.2%), decreased leukocytes (43%; 1.6%), decreased albumin (42%; 0.7%), decreased calcium (41%; 3.8%), increased creatinine (37%; 1.0%), increased alkaline phosphatase (36%; 2.3%), decreased platelets (33%; 2.7%), increased total cholesterol (31%; 0.1%), decreased sodium (27%; 7%), decreased magnesium (24%; 0.6%), increased potassium (24%; 1.2%), increased bilirubin (23%; 2.0%), and decreased glucose (22%; 0.7%).
Concomitant use of acid-reducing agents decrease selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid).
Concomitant use of strong and moderate CYP3A inhibitors increase selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of strong and moderate CYP3A inducers decrease selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers.
Concomitant use of Retevmo with CYP2C8 and CYP3A substrates increase their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling.
The safety and effectiveness of Retevmo have not been established in pediatric patients less than 12 years of age. The safety and effectiveness of Retevmo have been established in pediatric patients aged 12 years and older for medullary thyroid cancer (MTC) who require systemic therapy and for advanced RET fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate). Use of Retevmo for these indications is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients aged 12 years and older.
No dosage modification is recommended for patients with mild to moderate renal impairment (creatinine clearance [CLcr] ≥30 mL/Min, estimated by Cockcroft-Gault). A recommended dosage has not been established for patients with severe renal impairment or end-stage renal disease.
Reduce the dose when administering Retevmo to patients with severe hepatic impairment (total bilirubin greater than 3 to 10 times upper limit of normal [ULN] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment.
SE HCP ISI All_08MAY2020
Please see full Prescribing Information and Patient Prescribing Information for Retevmo.
IMPORTANT SAFETY INFORMATION FOR VERZENIO (abemaciclib)
Diarrhea occurred in 81% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 86% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 90% of patients receiving Verzenio alone in MONARCH 1. Grade 3 diarrhea occurred in 9% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 13% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 20% of patients receiving Verzenio alone in MONARCH 1. Episodes of diarrhea have been associated with dehydration and infection. Diarrhea incidence was greatest during the first month of Verzenio dosing. In MONARCH 3, the median time to onset of the first diarrhea event was 8 days, and the median duration of diarrhea for Grades 2 and 3 were 11 and 8 days, respectively. In MONARCH 2, the median time to onset of the first diarrhea event was 6 days, and the median duration of diarrhea for Grades 2 and 3 were 9 days and 6 days, respectively. In MONARCH 3, 19% of patients with diarrhea required a dose omission and 13% required a dose reduction. In MONARCH 2, 22% of patients with diarrhea required a dose omission and 22% required a dose reduction. The time to onset and resolution for diarrhea were similar across MONARCH 3, MONARCH 2, and MONARCH 1.
Instruct patients that at the first sign of loose stools, they should start antidiarrheal therapy such as loperamide, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow-up. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue Verzenio until toxicity resolves to ≤Grade 1, and then resume Verzenio at the next lower dose.
Neutropenia occurred in 41% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 46% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and 37% of patients receiving Verzenio alone in MONARCH 1. A Grade ≥3 decrease in neutrophil count (based on laboratory findings) occurred in 22% of patients receiving Verzenio plus an aromatase inhibitor in MONARCH 3, 32% of patients receiving Verzenio plus fulvestrant in MONARCH 2 and in 27% of patients receiving Verzenio alone in MONARCH 1. In MONARCH 3, the median time to first episode of Grade ≥3 neutropenia was 33 days, and in MONARCH 2 and MONARCH 1, was 29 days. In MONARCH 3, median duration of Grade ≥3 neutropenia was 11 days, and for MONARCH 2 and MONARCH 1 was 15 days.
Monitor complete blood counts prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.
Febrile neutropenia has been reported in
