INDIANAPOLIS, Sept. 23, 2019 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced data from a number of studies across the company's oncology product portfolio will be presented at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain, September 27 - October 1, 2019. Data from 14 oral presentations and posters – including five late-breaking abstracts – underscore Lilly Oncology's dedication to developing and delivering innovative new medicines that will make a meaningful difference to people living with cancer.
"Lilly's data to be presented at this year's ESMO truly embody the congress theme of 'translating science into better cancer patient care' in many ways, including the results demonstrating extension of life in women with advanced breast cancer and exciting data from our precision medicine portfolio," said Maura Dickler, M.D., vice president, late phase development, Lilly Oncology. "We are excited to present the statistically significant and clinically meaningful overall survival results for MONARCH 2, a study of Verzenio® plus fulvestrant for women living with HR+, HER2- advanced breast cancer whose cancer grew or spread following endocrine therapy, and registrational data from the LIBRETTO-001 study of our promising, highly selective and potent investigational agent selpercatinib (LOXO-292) in RET-altered thyroid cancers."
Lilly's Commitment to Advanced Breast Cancer Patients
Lilly continues to investigate Verzenio (abemaciclib) across the breast cancer continuum to provide physicians with the information they need as they seek to optimize treatment options for those living with this devastating, complex disease. At ESMO, Lilly will share detailed overall survival (OS) results from the Phase 3 MONARCH 2 trial, which demonstrated Verzenio plus fulvestrant significantly extended life in women with HR+, HER2- advanced breast cancer whose cancer grew or spread following endocrine therapy. Importantly, Verzenio had already shown a significant benefit for progression-free survival (PFS), the study's primary endpoint and basis for regulatory approvals globally. These OS results are to be presented in the ESMO Presidential Symposium and featured in the official ESMO Press Program.
Additional data to be presented include final results from the Phase 2 monarcHER trial evaluating Verzenio in combination with trastuzumab (with or without fulvestrant) in women with previously treated HR+, HER2+ advanced breast cancer. MonarcHER is the first randomized clinical trial of a CDK4 & 6 inhibitor for people with HER2+ advanced breast cancer, who represent approximately 15-20 percent of people living with advanced breast cancer. Findings from MONARCHplus, a Phase 3 trial with two cohorts evaluating the use of Verzenio plus an aromatase inhibitor and Verzenio plus fulvestrant (both versus placebo)—the first randomized clinical trial of a CDK4 & 6 inhibitor in a predominantly Chinese population of women with HR+, HER2- advanced breast cancer—to support registration in China, will also be presented.
Latest Results of Selpercatinib (LOXO-292)
In a late-breaking oral presentation, Lilly will share the registrational results of selpercatinib (LOXO-292) in RET-altered thyroid cancers, from the Phase 1/2 LIBRETTO-001 study. Selpercatinib is a highly selective and potent, oral investigational new medicine being studied for the treatment of advanced cancers that develop due to alterations of the RET kinase.
Selpercatinib is being investigated in RET fusion-positive cancers across tumor types and RET-mutant medullary thyroid cancer (MTC). RET fusions have been identified in approximately two percent of non-small cell lung cancer (NSCLC) patients, 10-20 percent of papillary thyroid cancer patients and a subset of other cancers. Activating RET point mutations account for approximately 60 percent of MTC. Results presented at ESMO, as well as the selpercatinib lung cancer data presented at the IASLC World Congress on Lung Cancer (WCLC) earlier this month, will be included as part of a new drug application submission to the U.S. Food and Drug Administration later this year.
Lung Cancer Data
Lilly has a strong heritage in developing practice-changing medicines for the treatment of lung cancer. Lilly has developed multiple thoracic oncology treatments and continues to study marketed products and investigational molecules in new combinations and settings where they could help specific patient populations. At ESMO, presentations include the first report of a biomarker study in Japanese patients from the Phase 3 RELAY trial and a pooled analysis of data from studies including KEYNOTE-021 and KEYNOTE-189 in patients with brain metastases, as well as tissue tumor mutation burden (tTMB) and outcomes from those same KEYNOTE studies.
RELAY is a global, randomized, double-blind Phase 3 trial evaluating CYRAMZA® (ramucirumab) in combination with erlotinib, compared to placebo in combination with erlotinib, as a first-line treatment in patients with metastatic NSCLC whose tumors have activating EGFR mutations. The RELAY study met its primary endpoint of PFS.
The global, randomized, double-blind Phase 3 KEYNOTE-189 study evaluated ALIMTA® (pemetrexed) in combination with KEYTRUDA® (pembrolizumab) and cisplatin or carboplatin compared with ALIMTA in combination with placebo and cisplatin or carboplatin, in untreated patients with metastatic nonsquamous NSCLC. KEYNOTE-189 enrolled patients regardless of PD-L1 expression and had dual primary endpoints of OS and PFS. The KEYNOTE-189 trial was based on results seen in the Phase 2 KEYNOTE-021 (Cohort G1) study. The KEYNOTE-189 and -021 trials were conducted by Merck (known as MSD outside the U.S. and Canada) in collaboration with Lilly.
Select studies, along with the dates, times and locations of their data sessions, are highlighted below.
Verzenio (abemaciclib)
Abstract # 1605: MONARCH 2: Overall survival of abemaciclib plus fulvestrant in patients with HR+, HER2- advanced breast cancer (George W. Sledge)
Proffered Paper Session: Presentation Number LBA6
Sunday, September 29, 2019; 16:30 - 18:00; Barcelona Auditorium (Hall 2)
Abstract # 1470: monarcHER: A randomized Phase 2 study of abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with HR+, HER2+ advanced breast cancer (ABC) (Sara M. Tolaney)
Proffered Paper Session: Presentation Number LBA23
Saturday, September 28, 2019; 10:15 - 11:45; Barcelona Auditorium (Hall 2)
Abstract # 1076: MONARCHplus: A Phase 3 Trial of Abemaciclib plus Nonsteroidal Aromatase Inhibitor (NSAI) or Fulvestrant (F) for Women with HR+/HER2- Advanced Breast Cancer (ABC) (Zefei Jiang)
Poster Discussion Session: Presentation Number LBA25
Sunday, September 29, 2019; 08:30 - 09:50; Cordoba Auditorium (Hall 7)
Abstract # 1378: MONARCH 3: Updated time to chemotherapy and disease progression following abemaciclib plus aromatase inhibitor (AI) in HR+, HER2- advanced breast cancer (ABC) (Miguel Martín)
Poster Display Session: Presentation Number 326P
Sunday, September 29, 2019; 12:00 - 13:00; Poster Area (Hall 4)
Abstract # 2777: A Phase 2 study of abemaciclib in patients (pts) with brain metastases (BM) secondary to non-small cell lung cancer (NSCLC) or melanoma (MEL). (Solmaz Sahebjam)
Poster Display Session: Presentation Number 331P
Sunday, September 29, 2019; 12:00 - 13:00; Poster Area (Hall 4)
Selpercatinib (LOXO-292)
Abstract # 2402: Registrational Results of LOXO-292 in Patients with RET-Altered Thyroid Cancers (Lori J. Wirth)
Proffered Paper Session: Presentation Number LBA93
Sunday, September 29, 2019; 16:30 - 18:00; Tarragona Auditorium (Hall 7)
CYRAMZA (ramucirumab)
Abstract # 2855: Impact of ramucirumab (RAM) + erlotinib (ERL) on EGFR mutations in circulating tumor DNA – The 1st report of a biomarker study in Japanese patients from RELAY: Global Ph3 study of ERL + RAM or placebo (PL) in 1L metastatic NSCLC with EGFR activating mutations (Kazuto Nishio)
Poster Display Session: Presentation Number 1523P
Saturday, September 28, 2019; 12:00 - 13:00; Poster Area (Hall 4)
Abstract # 1192: Ramucirumab in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha fetoprotein (AFP): An exposure–response analysis (Josep Llovet)
Poster Display Session: Presentation Number 758P
Sunday, September 29, 2019; 12:00 - 13:00; Poster Area (Hall 4)
Abstract # 1529: Prognostic and predictive value of baseline alpha-fetoprotein (AFP) in patients with advanced hepatocellular carcinoma (HCC) treated with ramucirumab from two phase 3 studies (REACH, REACH-2) (Andrew X. Zhu)
Poster Display Session: Presentation Number 753P
Sunday, September 29, 2019; 12:00 - 13:00; Poster Area (Hall 4)
Abstract # 1758: Efficacy and safety of ramucirumab (RAM) for advanced hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) following first-line sorafenib across age subgroups in two global phase 3 trials (REACH and REACH-2) (Masatoshi Kudo)
Poster Display Session: Presentation Number 757P
Sunday, September 29, 2019; 12:00 - 13:00; Poster Area (Hall 4)
Abstract # 2717: Ramucirumab use in patients with Advanced Gastric Cancer (AGC) or gastro-oesophageal junction (GEJ) adenocarcinoma in Spain: RAMIS observational study (Federico Longo Munoz)
Poster Display Session: Presentation Number 793P
Sunday, September 29, 2019; 12:00 - 13:00; Poster Area (Hall 4)
Abstract # 2108: Biomarker analyses of ramucirumab in patients with platinum refractory urothelial cancer from RANGE, a global, randomized, double-blind, phase 3 study. (Michiel S. Van der Heijden)
Poster Display Session: Presentation Number 929P
Monday, September 30, 2019; 12:00 - 13:00; Poster Area (Hall 4)
ALIMTA (pemetrexed)
Abstract # 4597: Pembrolizumab (pembro) plus platinum-based chemotherapy (chemo) in NSCLC with brain metastases: Pooled analysis of KEYNOTE-021, 189, and 407 (Steven F. Powell)
Poster Discussion Session: Presentation Number 1483PD
Sunday, September 29, 2019; 16:30 - 17:45; Cordoba Auditorium (Hall 7)
Abstract # 4311: Pembrolizumab (pembro) plus platinum-based chemotherapy (chemo) for metastatic NSCLC: tissue TMB (tTMB) and outcomes in KEYNOTE-021, 189, and 407 (Luis Paz-Ares)
Proffered Paper Session: Presentation Number LBA80
Friday, September 27, 2019; 16:00 - 17:30; Barcelona Auditorium (Hall 2)
Notes to Editors
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.
About Selpercatinib (LOXO-292)
Selpercatinib, also known as LOXO-292, is a highly selective and potent, oral investigational new medicine in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. RET fusions and mutations occur across multiple tumor types with varying frequency. Selpercatinib was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms.
Selpercatinib has received breakthrough designation for the treatment of patients with:
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.
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.
INDICATION FOR VERZENIO
Verzenio is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer:
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 <1% of patients exposed to Verzenio in the MONARCH studies. Two deaths due to neutropenic sepsis were observed in MONARCH 2. Inform patients to promptly report any episodes of fever to their healthcare provider.
Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with Verzenio and other CDK4/6 inhibitors. Across clinical trials (MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of Verzenio-treated patients had ILD/pneumonitis of any grade, 0.6% had Grade 3 or 4, and 0.4% had fatal outcomes. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.
Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded by means of appropriate investigations.
Dose interruption or dose reduction is recommended in patients who develop persistent or recurrent Grade 2 ILD/pneumonitis. Permanently discontinue Verzenio in all patients with grade 3 or 4 ILD/pneumonitis.
Grade ≥3 increases in alanine aminotransferase (ALT) (6% versus 2%) and aspartate aminotransferase (AST) (3% versus 1%) were reported in the Verzenio and placebo arms, respectively, in MONARCH 3. Grade ≥3 increases in ALT (4% versus 2%) and AST (2% versus 3%) were reported in the Verzenio and placebo arms respectively, in MONARCH 2.
In MONARCH 3, for patients receiving Verzenio plus an aromatase inhibitor with Grade ≥3 increases in ALT or AST, median time to onset was 61 and 71 days, respectively, and median time to resolution to Grade <3 was 14 and 15 days, respectively. In MONARCH 2, for patients receiving Verzenio plus fulvestrant with Grade ≥3 increases in ALT or AST, median time to onset was 57 and 185 days, respectively, and median time to resolution to Grade <3 was 14 and 13 days, respectively.
For assessment of potential hepatotoxicity, monitor liver function tests (LFTs) 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, dose discontinuation, or delay in starting treatment cycles is recommended for patients who develop persistent or recurrent Grade 2, or Grade 3 or 4, hepatic transaminase elevation.
Venous thromboembolic events were reported in 5% of patients treated with Verzenio plus an aromatase inhibitor as compared to 0.6% of patients treated with an aromatase inhibitor plus placebo in MONARCH 3. Venous thromboembolic events were reported in 5% of patients treated with Verzenio plus fulvestrant in MONARCH 2 as compared to 0.9% of patients treated with fulvestrant plus placebo. Venous thromboembolic events included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. Across the clinical development program, deaths due to venous thromboembolism have been reported. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate.
Verzenio can cause fetal harm when administered to a pregnant woman based on findings from animal studies and the mechanism of action. In animal reproduction studies, administration of abemaciclib to pregnant rats during the period of organogenesis caused teratogenicity and decreased fetal weight at maternal exposures that were similar to the human clinical exposure based on area under the curve (AUC) at the maximum recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Verzenio and for at least 3 weeks after the last dose. There are no data on the presence of Verzenio in human milk or its effects on the breastfed child or on milk production. Advise lactating women not to breastfeed during Verzenio treatment and for at least 3 weeks after the last dose because of the potential for serious adverse reactions in breastfed infants. Based on findings in animals, Verzenio may impair fertility in males of reproductive potential.
The most common adverse reactions (all grades, ≥10%) observed in MONARCH 3 for Verzenio plus anastrozole or letrozole and ≥2% higher than placebo plus anastrozole or letrozole vs placebo plus anastrozole or letrozole were diarrhea (81% vs 30%), neutropenia (41% vs 2%), fatigue (40% vs 32%), infections (39% vs 29%), nausea (39% vs 20%), abdominal pain (29% vs 12%), vomiting (28% vs 12%), anemia (28% vs 5%), alopecia (27% vs 11%), decreased appetite (24% vs 9%), leukopenia (21% vs 2%), creatinine increased (19% vs 4%), constipation (16% vs 12%), ALT increased (16% vs 7%), AST increased (15% vs 7%), rash (14% vs 5%), pruritus (13% vs 9%), cough (13% vs 9%), dyspnea (12% vs 6%), dizziness (11% vs 9%), weight decreased (10% vs 3%), influenza-like illness (10% vs 8%), and thrombocytopenia (10% vs 2%).
The most common adverse reactions (all grades, ≥10%) observed in MONARCH 2 for Verzenio plus fulvestrant and ≥2% higher than placebo plus fulvestrant vs placebo plus fulvestrant were diarrhea (86% vs 25%), neutropenia (46% vs 4%), fatigue (46% vs 32%), nausea (45% vs 23%), infections (43% vs 25%), abdominal pain (35% vs 16%), anemia (29% vs 4%), leukopenia (28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs 10%), headache (20% vs 15%), dysgeusia (18% vs 3%), thrombocytopenia (16% vs 3%), alopecia (16% vs 2%), stomatitis (15% vs 10%), ALT increased (13% vs 5%), pruritus (13% vs 6%), cough (13% vs 11%), dizziness (12% vs 6%), AST increased (12% vs 7%), peripheral edema (12% vs 7%), creatinine increased (12% vs <1%), rash (11% vs 4%), pyrexia (11% vs 6%), and weight decreased (10% vs 2%).
The most common adverse reactions (all grades, ≥10%) observed in MONARCH 1 with Verzenio were diarrhea (90%), fatigue (65%), nausea (64%), decreased appetite (45%), abdominal pain (39%), neutropenia (37%), vomiting (35%), infections (31%), anemia (25%), thrombocytopenia (20%), headache (20%), cough (19%), leukopenia (17%), constipation (17%), arthralgia (15%), dry mouth (14%), weight decreased (14%), stomatitis (14%), creatinine increased (13%), alopecia (12%), dysgeusia (12%), pyrexia (11%), dizziness (11%), and dehydration (10%).
The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 3 were neutropenia (22% vs 2%), diarrhea (9% vs 1%), leukopenia (8% vs <1%), ALT increased (7% vs 2%), and anemia (6% vs 1%).
The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 2 were neutropenia (27% vs 2%), diarrhea (13% vs <1%), leukopenia (9% vs 0%), anemia (7% vs 1%), and infections (6% vs 3%).
The most frequently reported ≥5% Grade 3 or 4 adverse reactions from MONARCH 1 with Verzenio were neutropenia (24%), diarrhea (20%), fatigue (13%), infections (7%), leukopenia (6%), anemia (5%), and nausea (5%).
Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 3 in ≥10% for Verzenio plus anastrozole or letrozole and ≥2% higher than placebo plus anastrozole or letrozole vs placebo plus anastrozole or letrozole were increased serum creatinine (98% vs 84%; 2% vs 0%), decreased white blood cells (82% vs 27%; 13% vs <1%), anemia (82% vs 28%; 2% vs 0%), decreased neutrophil count (80% vs 21%; 22% vs 3%), decreased lymphocyte count (53% vs 26%; 8% vs 2%), decreased platelet count (36% vs 12%; 2% vs <1%), increased ALT (48% vs 25%; 7% vs 2%), and increased AST (37% vs 23%; 4% vs <1%).
Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 2 in ≥10% for Verzenio plus fulvestrant and ≥2% higher than placebo plus fulvestrant vs placebo plus fulvestrant were increased serum creatinine (98% vs 74%; 1% vs 0%), decreased white blood cells (90% vs 33%; 23% vs 1%), decreased neutrophil count (87% vs 30%; 33% vs 4%), anemia (84% vs 33%; 3% vs <1%), decreased lymphocyte count (63% vs 32%; 12% vs 2%), decreased platelet count (53% vs 15%; 2% vs 0%), increased ALT (41% vs 32%; 5% vs 1%), and increased AST (37% vs 25%; 4% vs 4%).
Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 1 with Verzenio were increased serum creatinine (98%; <1%), decreased white blood cells (91%; 28%), decreased neutrophil count (88%; 27%), anemia (68%; 0%), decreased lymphocyte count (42%; 14%), decreased platelet count (41%; 2%), increased ALT (31%; 3%), and increased AST (30%; 4%).
Strong and moderate CYP3A inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity. Avoid concomitant use of the strong CYP3A inhibitor ketoconazole. Ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold. In patients with recommended starting doses of 200 mg twice daily or 150 mg twice daily, reduce the Verzenio dose to 100 mg twice daily with concomitant use of strong CYP3A inhibitors other than ketoconazole. In patients who have had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the Verzenio dose to 50 mg twice daily with concomitant use of strong CYP3A inhibitors. If a patient taking Verzenio discontinues a strong CYP3A inhibitor, increase the Verzenio dose (after 3 to 5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor. With concomitant use of moderate CYP3A inhibitors, monitor for adverse reactions and consider reducing the Verzenio dose in 50 mg decrements. Patients should avoid grapefruit products.
Avoid concomitant use of strong or moderate CYP3A inducers and consider alternative agents. Coadministration of strong or moderate CYP3A inducers decreased the plasma concentrations of abemaciclib plus its active metabolites and may lead to reduced activity.
With severe hepatic impairment (Child-Pugh Class C), reduce the Verzenio dosing frequency to once daily. The pharmacokinetics of Verzenio in patients with severe renal impairment (CLcr <30 mL/min), end stage renal disease, or in patients on dialysis is unknown. No dosage adjustments are necessary in patients with mild or moderate hepatic (Child-Pugh A or B) and/or renal impairment (CLcr ≥30-89 mL/min).
AL HCP ISI 17SEP2019
Please see full Prescribing Information for Verzenio.
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 Cancer
CYRAMZA, 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 Carcinoma
CYRAMZA, 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.
IMPORTANT SAFETY INFORMATION FOR CYRAMZA® (ramucirumab)
Warnings and Precautions
Hemorrhage
Gastrointestinal Perforations
Impaired Wound Healing
Arterial Thromboembolic Events
Hypertension
Infusion-Related Reactions
Worsening of Pre-existing Hepatic Impairment
Reversible Posterior Leukoencephalopathy Syndrome
Proteinuria Including Nephrotic Syndrome
Thyroid Dysfunction
Embryo-Fetal Toxicity
Lactation
Most Common Adverse Reactions—CYRAMZA Administered as a Single Agent (REGARD)
Most Common Adverse Reactions— CYRAMZA Administered in Combination with Paclitaxel (RAINBOW)
Most Common Adverse Reactions— CYRAMZA Administered in Combination with Docetaxel (REVEL)
Most Common Adverse Reactions— CYRAMZA Administered in Combination with FOLFIRI (RAISE)
Most Common Adverse Reactions— CYRAMZA Administered as a Single Agent (REACH-2)
RB-P HCP ISI 08AUG2019
Please see full Prescribing Information for CYRAMZA.
IMPORTANT SAFETY INFORMATION FOR ALIMTA® (pemetrexed for injection)
CONTRAINDICATION
WARNINGS AND PRECAUTIONS
Myelosuppression and Increased Risk of Myelosuppression Without Vitamin Supplementation
Renal Failure
Bullous and Exfoliative Skin Toxicity
Interstitial Pneumonitis
Radiation Recall
Increased Risk of Toxicity With Ibuprofen in Patients With Renal Impairment
Embryo-Fetal Toxicity
DRUG INTERACTIONS
ADVERSE REACTIONS
USE IN SPECIFIC PATIENT POPULATIONS
PM_HCP_ISI_NSCLC1L_Combo_30JAN2019
For safety and dosing guidelines for ALIMTA, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information and Patient Prescribing Information.
About Lilly Oncology
For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly's commitment to people with cancer, please visit www.LillyOncology.com.
About Eli Lilly and Company
Lilly is a global health care leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.com and lilly.com/newsroom. P-LLY
© Lilly USA, LLC 2019. ALL RIGHTS RESERVED.
Verzenio®, CYRAMZA®, and ALIMTA® are registered trademarks owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Fulvestrant (Faslodex®), MedImmune/AstraZeneca. MedImmune Limited/AstraZeneca provided fulvestrant for the MONARCH 2 trial.
Lilly Forward-Looking Statement
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Lilly's oncology portfolio and pipeline, including Verzenio, selpercatinib (LOXO-292), CYRAMZA and ALIMTA, and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date or that Verzenio, selpercatinib (LOXO-292), CYRAMZA or ALIMTA will receive (or receive additional) regulatory approvals or be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
1 PINN, pending USAN approval
Refer to: | Tracy Henrikson; tracy.henrikson@lilly.com; 609-454-7116 (Lilly) – media |
Kevin Hern; hern_kevin_r@lilly.com; 317-277-1838 (Lilly) – investors |
SOURCE Eli Lilly and Company