Bayer to Highlight New Research at ESMO 2017 Congress

Abstracts: 807P, 416P, 534P, 1198P, 625PD, 380P, 1513P, 705P, 702P, 706P, 465P, 1034TiP, 1000PD, 1001PD, 838TiP, 424TiP, 859P, 379P

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Bayer

Sep 01, 2017, 03:00 ET

WHIPPANY, N.J., Sept. 1, 2017 /PRNewswire/ -- Bayer will present the latest research from across its growing oncology portfolio at the European Society for Medical Oncology (ESMO) 2017 Congress, September 8-12 in Madrid, Spain. The studies presented will include new preclinical and clinical data on Bayer's marketed portfolio and late-stage compounds as well as research from two earlier pipeline projects.

"We value the opportunity to meet with some of the best minds in cancer research at ESMO," said Carsten Brunn, Head of Pharmaceuticals, Americas Region at Bayer. "This year's ESMO theme is all about integrating science into oncology to improve patient outcomes – a fitting topic given where we're at as an industry, and a company. Our scientific discovery and research is powered to impact the lives of patients with difficult-to-treat cancers."

The Bayer data include results from two ongoing trials for Xofigo^® (radium Ra 223 dichloride) injection, including an interim analysis from the observational REASSURE trial, analyzing real-world metastatic castration-resistant prostate cancer patient characteristics and safety profile. Multiple analyses of the Phase III RESORCE trial in hepatocellular carcinoma (HCC) will be presented.

Bayer will also present subgroup results from the pivotal Phase II CHRONOS-1 study in patients with relapsed or refractory indolent B-cell non-Hodgkin's lymphoma (iNHL). Additionally, early research from rogaritinib, the company's investigational pan-FGFR inhibitor, will be presented.

See below for a full listing of Bayer studies to be featured at the ESMO 2017 Congress:

Radium-223 Dichloride (radium-223)

First interim results of the radium-223 (Ra-223) REASSURE observational study: Analysis of patient (Pt) characteristics and safety by use of abiraterone and / or enzalutamide (Abi / Enza)

Abstract 807P, Session: Poster Display Session
Date: September 10, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

An open-label, multicenter phase Ib study of radium-223 + paclitaxel in cancer patients with bone metastases

Abstract 416P, Session: Poster Display Session
Date: September 11, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Regorafenib

Exploratory analysis of baseline microsatellite instability (MSI) status in patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) or placebo in the phase 3 CORRECT trial

Abstract 534P, Session: Poster Display Session
Date: September 9, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Circulating miRNA biomarkers predicting regorafenib (REG) clinical benefit in patients with hepatocellular carcinoma (HCC) in the RESORCE trial

Abstract 705P, Session: Poster Display Session
Date: September 9, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Immunomodulation by regorafenib alone and in combination with anti PD1 antibody on murine models of colorectal cancer

Abstract 1198P, Session: Poster Display Session
Date: September 10, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Tumor growth rate analysis of progression-free survival (PFS) and overall survival (OS) for patients with metastatic and / or unresectable gastrointestinal stromal tumors (GIST) receiving placebo or regorafenib in the phase 3 GRID trial

Abstract 1513P, Session: Poster Display Session
Date: September 11, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Protein biomarkers as predictors of outcome with regorafenib (REG) in patients (pts) with hepatocellular carcinoma (HCC) in the RESORCE trial

Abstract 625PD, Session: Poster Discussion Session
Date: September 11, 2017, Time: 5:20 pm - 5:40 pm CEST
Location: Cordoba Auditorium

A phase Ib study evaluating the safety and pharmacokinetics (PK) of regorafenib (REG) in combination with cetuximab (CTX) in patients with advanced solid tumors

Abstract 380P, Session: Poster Display Session
Date: September 11, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Sorafenib

Correlation between overall survival (OS) and time to progression (TTP) and between OS and response rate (RR) by RECIST in advanced hepatocellular carcinoma (HCC)

Abstract 702P, Session: Poster Display Session
Date: September 9, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Overall survival (OS) by platelet count at baseline in patients with hepatocellular carcinoma (HCC) treated with sorafenib (SOR) in the SHARP and AP trials and regorafenib (REG) in the RESORCE trial

Abstract 706P, Session: Poster Display Session
Date: September 9, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Interim baseline characteristics from RIFTOS MKI, a global non-interventional study assessing the use of multikinase inhibitors (MKIs) in the treatment of patients with asymptomatic radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC): A European subgroup analysis

Abstract 465P, Session: Poster Display Session
Date: September 10, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Copanlisib

Phase III randomized, double-blind, controlled studies of the PI3K inhibitor copanlisib in combination with rituximab or rituximab-based chemotherapy in subjects with relapsed indolent B-cell non-Hodgkin's lymphoma (iNHL): CHRONOS-3 and CHRONOS-4

Trial in Progress: Abstract 1034TiP, Session: Poster Display Session
Date: September 9, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Copanlisib treatment in patients with relapsed or refractory indolent B-cell lymphoma: Subgroup analyses from the CHRONOS-1 study

Abstract 1000PD, Session: Poster Discussion Session
Date: September 11, 2017, Time: 4:50 pm - 5:10 pm CEST
Location: Tarragona Auditorium

Tumor gene expression signatures of BCR/PI3K dependence in association with copanlisib monotherapy activity in heavily pretreated patients with indolent NHL and follicular lymphoma

Abstract 1001PD, Session: Poster Discussion Session
Date: September 11, 2017, Time: Time: 4:50 pm - 5:10 pm CEST
Location: Tarragona Auditorium

Darolutamide

ARASENS: A Phase 3 Trial of Darolutamide in Males With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Trial in Progress: Abstract 838TiP, Session: Poster Display Session
Date: September 10, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Anetumab

Phase Ib multi-indication study of the antibody drug conjugate anetumab ravtansine in patients with mesothelin-expressing advanced or recurrent malignancies

Trial in Progress: Abstract 424TiP, Session: Poster Display Session
Date: September 11, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

Rogaratinib

Anti-tumor activity of the pan-FGFR inhibitor rogaratinib in patients with advanced urothelial carcinomas selected based on tumor FGFR mRNA expression levels

Abstract 859P, Session: Poster Display Session
Date: September 10, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

A novel mRNA-based patient selection strategy identifies fibroblast growth factor receptor (FGFR) inhibitor-sensitive tumors: Results from rogaratinib Phase-1 study

Abstract 379P, Session: Poster Display Session
Date: September 11, 2017, Time: 1:15 pm - 2:15 pm CEST
Location: Hall 8

About Xofigo^® (radium Ra 223 dichloride) Injection
Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.¹

Important Safety Information for Xofigo^® (radium Ra 223 dichloride) Injection

Contraindications: Xofigo is contraindicated in women who are or may become pregnant. Xofigo can cause fetal harm when administered to a pregnant woman.
Bone Marrow Suppression: In the randomized trial, 2% of patients in the Xofigo arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with Xofigo bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the Xofigo arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (<1%) was similar for patients treated with Xofigo and placebo. Myelosuppression – notably thrombocytopenia, neutropenia, pancytopenia, and leucopenia – has been reported in patients treated with Xofigo.
Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for bone marrow failure.
Hematological Evaluation: Monitor blood counts at baseline and prior to every dose of Xofigo. Prior to first administering Xofigo, the absolute neutrophil count (ANC) should be greater than or equal to 1.5 × 10⁹/L, the platelet count greater than or equal to 100 × 10⁹/L, and hemoglobin greater than or equal to 10 g/dL. Prior to subsequent administrations, the ANC should be greater than or equal to 1 × 10⁹/L and the platelet count greater than or equal to 50 × 10⁹/L. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care.
Concomitant Use with Chemotherapy: Safety and efficacy of concomitant chemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use of Xofigo in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued.
Administration and Radiation Protection: Xofigo should be received, used, and administered only by authorized persons in designated clinical settings. The administration of Xofigo is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations.
Fluid Status: Dehydration occurred in 3% of patients on Xofigo and 1% of patients on placebo. Xofigo increases adverse reactions such as diarrhea, nausea, and vomiting, which may result in dehydration. Monitor patients' oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of dehydration or hypovolemia.
Injection Site Reactions: Erythema, pain, and edema at the injection site were reported in 1% of patients on Xofigo.
Secondary Malignant Neoplasms: Xofigo contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects. Due to its mechanism of action and neoplastic changes, including osteosarcomas, in rats following administration of radium -223 dichloride, Xofigo may increase the risk of osteosarcoma or other secondary malignant neoplasms. However, the overall incidence of new malignancies in the randomized trial was lower on the Xofigo arm compared to placebo (<1% vs 2%; respectively), but the expected latency period for the development of secondary malignancies exceeds the duration of follow up for patients on the trial.
Subsequent Treatment with Cytotoxic Chemotherapy: In the randomized clinical trial, 16% patients in the Xofigo group and 18% patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with Xofigo will tolerate subsequent cytotoxic chemotherapy.
Adverse Reactions: The most common adverse reactions (≥10%) in the Xofigo arm vs the placebo arm, respectively, were nausea (36% vs 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheral edema (13% vs 10%). Grade 3 and 4 adverse events were reported in 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in the Xofigo arm (≥10%) vs the placebo arm, respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs 53%), leukopenia (35% vs 10%), thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%).

For full Prescribing Information visit http://labeling.bayerhealthcare.com/html/products/pi/Xofigo_PI.pdf.

About Stivarga^® (regorafenib)
In April 2017, Stivarga was approved for use in patients with hepatocellular carcinoma who have been previously treated with Nexavar^®(sorafenib). In the United States, Stivarga is also indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy. It is also indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.²

Regorafenib is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.

Important Safety Information

WARNING: HEPATOTOXICITY

Severe and sometimes fatal hepatotoxicity has occurred in clinical trials.
Monitor hepatic function prior to and during treatment.
Interrupt and then reduce or discontinue STIVARGA for hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis, depending upon severity and persistence.

Hepatotoxicity: Severe drug-induced liver injury with fatal outcome occurred in STIVARGA-treated patients across all clinical trials. In most cases, liver dysfunction occurred within the first 2 months of therapy and was characterized by a hepatocellular pattern of injury. In metastatic colorectal cancer (mCRC), fatal hepatic failure occurred in 1.6% of patients in the STIVARGA arm and in 0.4% of patients in the placebo arm. In gastrointestinal stromal tumor (GIST), fatal hepatic failure occurred in 0.8% of patients in the STIVARGA arm. In hepatocellular carcinoma (HCC), there was no increase in the incidence of fatal hepatic failure as compared to placebo.

Liver Function Monitoring: Obtain liver function tests (ALT, AST, and bilirubin) before initiation of STIVARGA and monitor at least every 2 weeks during the first 2 months of treatment. Thereafter, monitor monthly or more frequently as clinically indicated. Monitor liver function tests weekly in patients experiencing elevated liver function tests until improvement to less than 3 times the upper limit of normal (ULN) or baseline values. Temporarily hold and then reduce or permanently discontinue STIVARGA, depending on the severity and persistence of hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis.

Infections: STIVARGA caused an increased risk of infections. The overall incidence of infection (Grades 1-5) was higher (32% vs 17%) in 1142 STIVARGA-treated patients as compared to the control arm in randomized placebo-controlled trials. The incidence of grade 3 or greater infections in STIVARGA treated patients was 9%. The most common infections were urinary tract infections (5.7%), nasopharyngitis (4.0%), mucocutaneous and systemic fungal infections (3.3%) and pneumonia (2.6%). Fatal outcomes caused by infection occurred more often in patients treated with STIVARGA (1.0%) as compared to patients receiving placebo (0.3%); the most common fatal infections were respiratory (0.6% vs 0.2%). Withhold STIVARGA for Grade 3 or 4 infections, or worsening infection of any grade. Resume STIVARGA at the same dose following resolution of infection.

Hemorrhage: STIVARGA caused an increased incidence of hemorrhage. The overall incidence (Grades 1-5) was 18.2% in 1142 patients treated with STIVARGA vs 9.5% with placebo in randomized, placebo-controlled trials. The incidence of grade 3 or greater hemorrhage in patients treated with STIVARGA was 3.0%. The incidence of fatal hemorrhagic events was 0.7%, involving the central nervous system or the respiratory, gastrointestinal, or genitourinary tracts. Permanently discontinue STIVARGA in patients with severe or life-threatening hemorrhage and monitor INR levels more frequently in patients receiving warfarin.

Gastrointestinal Perforation or Fistula: Gastrointestinal perforation occurred in 0.6% of 4518 patients treated with STIVARGA across all clinical trials of STIVARGA administered as a single agent; this included eight fatal events. Gastrointestinal fistula occurred in 0.8% of patients treated with STIVARGA and in 0.2% of patients in the placebo arm across randomized, placebo-controlled trials. Permanently discontinue STIVARGA in patients who develop gastrointestinal perforation or fistula.

Dermatological Toxicity: In randomized, placebo-controlled trials, adverse skin reactions occurred in 71.9% of patients with STIVARGA arm and 25.5% of patients in the placebo arm including hand-foot skin reaction (HFSR) also known as palmar-plantar erythrodysesthesia syndrome (PPES) and severe rash, requiring dose modification. In the randomized, placebo-controlled trials, the overall incidence of HFSR was higher in 1142 STIVARGA-treated patients (53% vs 8%) than in the placebo-treated patients. Most cases of HFSR in STIVARGA-treated patients appeared during the first cycle of treatment. The incidences of Grade 3 HFSR (16% vs <1%), Grade 3 rash (3% vs <1%), serious adverse reactions of erythema multiforme (<0.1% vs 0%), and Stevens-Johnson syndrome (<0.1% vs 0%) were higher in STIVARGA-treated patients. Across all trials, a higher incidence of HFSR was observed in Asian patients treated with STIVARGA (all grades: 72%; Grade 3:18%). Toxic epidermal necrolysis occurred in 0.02% of 4518 STIVARGA-treated patients across all clinical trials of STIVARGA administered as a single agent. Withhold STIVARGA, reduce the dose, or permanently discontinue depending on the severity and persistence of dermatologic toxicity.

Hypertension: Hypertensive crisis occurred in 0.2% in STIVARGA-treated patients and in none of the patients in placebo arm across all randomized, placebo-controlled trials. STIVARGA caused an increased incidence of hypertension (30% vs 8% in mCRC, 59% vs 27% in GIST, and 31% vs 6% in HCC). The onset of hypertension occurred during the first cycle of treatment in most patients who developed hypertension (67% in randomized, placebo controlled trials). Do not initiate STIVARGA until blood pressure is adequately controlled. Monitor blood pressure weekly for the first 6 weeks of treatment and then every cycle, or more frequently, as clinically indicated. Temporarily or permanently withhold STIVARGA for severe or uncontrolled hypertension.

Cardiac Ischemia and Infarction: STIVARGA increased the incidence of myocardial ischemia and infarction (0.9% with STIVARGA vs 0.2% with placebo) in randomized placebo-controlled trials. Withhold STIVARGA in patients who develop new or acute cardiac ischemia or infarction, and resume only after resolution of acute cardiac ischemic events if the potential benefits outweigh the risks of further cardiac ischemia.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Reversible posterior leukoencephalopathy syndrome (RPLS), a syndrome of subcortial vasogenic edema diagnosed by characteristic finding on MRI occurred in one of 4800 STIVARGA-treated patients across all clinical trials. Perform an evaluation for RPLS in any patient presenting with seizures, severe headache, visual disturbances, confusion, or altered mental function. Discontinue STIVARGA in patients who develop RPLS.

Wound Healing Complications: Treatment with STIVARGA should be stopped at least 2 weeks prior to scheduled surgery. Resuming treatment after surgery should be based on clinical judgment of adequate wound healing. STIVARGA should be discontinued in patients with wound dehiscence.

Embryo-Fetal Toxicity: STIVARGA can cause fetal harm when administered to a pregnant woman. There are no available data on STIVARGA use in pregnant women. 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 STIVARGA and for 2 months after the final dose.

Nursing Mothers: Because of the potential for serious adverse reactions in breastfed infants from STIVARGA, do not breastfeed during treatment with STIVARGA and for 2 weeks after the final dose.

Most Frequently Observed Adverse Drug Reactions in mCRC (≥30%): The most frequently observed adverse drug reactions (≥30%) in STIVARGA-treated patients vs placebo-treated patients in mCRC, respectively, were: asthenia/fatigue (64% vs 46%), pain (59% vs 48%), decreased appetite and food intake (47% vs 28%), HFSR/PPE (45% vs 7%), diarrhea (43% vs 17%), mucositis (33% vs 5%), weight loss (32% vs 10%), infection (31% vs 17%), hypertension (30% vs 8%), and dysphonia (30% vs 6%).

Most Frequently Observed Adverse Drug Reactions in GIST (≥30%): The most frequently observed adverse drug reactions (≥30%) in STIVARGA-treated patients vs placebo-treated patients in GIST, respectively, were: HFSR/PPE (67% vs 12%), pain (60% vs 55%), hypertension (59% vs 27%), asthenia/fatigue (52% vs 39%), diarrhea (47% vs 9%), mucositis (40% vs 8%), dysphonia (39% vs 9%), infection (32% vs 5%), decreased appetite and food intake (31% vs 21%), and rash (30% vs 3%).

Most Frequently Observed Adverse Drug Reactions in HCC (≥30%): The most frequently observed adverse drug reactions (≥30%) in STIVARGA-treated patients vs placebo-treated patients in HCC, respectively, were: pain (55% vs 44%), HFSR/PPE (51% vs 7%), asthenia/fatigue (42% vs 33%), diarrhea (41% vs 15%), hypertension (31% vs 6%), infection (31% vs 18%), decreased appetite and food intake (31% vs 15%).

Please see full Prescribing Information, including Boxed Warning.

About NEXAVAR^® (sorafenib) Tablets
NEXAVAR is approved in the U.S. for the treatment of patients with unresectable hepatocellular carcinoma, patients with advanced renal cell carcinoma and patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.³

Important Safety Considerations For NEXAVAR^® (sorafenib) Tablets

NEXAVAR is contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of NEXAVAR
NEXAVAR in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer
Cardiac ischemia and/or myocardial infarction may occur. The incidence of cardiac ischemia/infarction in NEXAVAR-treated vs placebo-treated patients was 2.7% vs 1.3%, 2.9% vs 0.4%, and 1.9% vs 0% in the HCC, RCC, and DTC studies, respectively. Temporary or permanent discontinuation of NEXAVAR should be considered in patients who develop cardiac ischemia and/or myocardial infarction
An increased risk of bleeding may occur following NEXAVAR administration. The following bleeding adverse reactions were reported in the NEXAVAR-treated vs placebo-treated patients, respectively, in the HCC study: bleeding from esophageal varices (2.4% vs 4%) and bleeding with fatal outcome at any site (2.4% vs 4%); in the RCC study: bleeding regardless of causality (15.3% vs 8.2%), Grade 3 bleeding (2.0% vs 1.3%), Grade 4 bleeding (0% vs 0.2%), and one fatal hemorrhage in each treatment group; in the DTC study: bleeding (17.4% vs 9.6%) and Grade 3 bleeding (1% vs 1.4%).There was no Grade 4 bleeding reported and there was one fatal hemorrhage in a placebo-treated patient. If bleeding necessitates medical intervention, consider permanent discontinuation of NEXAVAR. Due to the potential risk of bleeding, tracheal, bronchial, and esophageal infiltration should be treated with local therapy prior to administering NEXAVAR in patients with DTC
Monitor blood pressure weekly during the first 6 weeks and periodically thereafter, and treat, if required. In the HCC study, hypertension was reported in approximately 9.4% of NEXAVAR-treated patients and 4.3% of patients in the placebo-treated group. In the RCC study, hypertension was reported in approximately 16.9% of NEXAVAR-treated patients and 1.8% of patients in the placebo-treated group. In the DTC study, hypertension was reported in 40.6% of NEXAVAR-treated patients and 12.4% of the placebo-treated patients. Hypertension was usually mild to moderate, occurred early in the course of treatment, and was managed with standard antihypertensive therapy. In cases of severe or persistent hypertension despite institution of antihypertensive therapy, consider temporary or permanent discontinuation of NEXAVAR
Hand-foot skin reaction and rash are the most common adverse reactions attributed to NEXAVAR. Management may include topical therapies for symptomatic relief. In cases of any severe or persistent adverse reactions, temporary treatment interruption, dose modification, or permanent discontinuation of NEXAVAR should be considered. There have been reports of severe dermatologic toxicities, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These cases may be life-threatening. Discontinue NEXAVAR if SJS or TEN are suspected
Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking NEXAVAR. Discontinue NEXAVAR in the event of a gastrointestinal perforation
Infrequent bleeding or elevations in the International Normalized Ratio (INR) have been reported in some patients taking warfarin while on NEXAVAR. Monitor patients taking concomitant warfarin regularly for changes in prothrombin time (PT), INR, or clinical bleeding episodes
Temporary interruption of NEXAVAR therapy is recommended in patients undergoing major surgical procedures
In a subset analysis of two randomized controlled trials in chemo-naïve patients with Stage IIIB-IV non-small cell lung cancer, patients with squamous cell carcinoma experienced higher mortality with the addition of NEXAVAR compared to those treated with carboplatin/paclitaxel alone (HR 1.81, 95% CI 1.19–2.74) and gemcitabine/cisplatin alone (HR 1.22, 95% CI 0.82-1.80). NEXAVAR, in combination with gemcitabine/cisplatin, is not recommended in patients with squamous cell lung cancer. The safety and effectiveness of NEXAVAR has not been established in patients with non-small cell lung cancer
NEXAVAR can prolong the QT/QTc interval and increase the risk for ventricular arrhythmias. Avoid use in patients with congenital long QT syndrome and monitor electrolytes and electrocardiograms in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics, and electrolyte abnormalities. Correct electrolyte abnormalities (magnesium, potassium, calcium). Interrupt NEXAVAR if QTc interval is greater than 500 milliseconds or for an increase from baseline of 60 milliseconds or greater
Sorafenib-induced hepatitis is characterized by a hepatocellular pattern of liver damage with significant increases of transaminases which may result in hepatic failure and death. Increases in bilirubin and INR may also occur. Liver function tests should be monitored regularly and in cases of increased transaminases without alternative explanation NEXAVAR should be discontinued
NEXAVAR may cause fetal harm when administered to a pregnant woman. Women of child-bearing potential should be advised to avoid becoming pregnant while on NEXAVAR
Female patients should be advised against breastfeeding while receiving NEXAVAR
In DTC, NEXAVAR impairs exogenous thyroid suppression. Elevation of thyroid stimulating hormone (TSH) level above 0.5 mU/L was observed in 41% of NEXAVAR-treated patients as compared with 16% of placebo-treated patients in the DTC study. For patients with impaired TSH suppression while receiving NEXAVAR, the median maximal TSH was 1.6 mU/L and 25% had TSH levels greater than 4.4 mU/L. Monitor TSH levels monthly and adjust thyroid replacement medication as needed in patients with DTC
In the HCC study, the most common laboratory abnormalities observed in the NEXAVAR arm versus the placebo arm, respectively, were hypoalbuminemia (59% vs 47%), lymphopenia (47% vs 42%), thrombocytopenia (46% vs 41%), elevation in INR (42% vs 34%), elevated lipase (40% vs 37%), hypophosphatemia (35% vs 11%), elevated amylase (34% vs 29%), hypocalcemia (27% vs 15%), and hypokalemia (9.5% vs 5.9%)
In the RCC study, the most common laboratory abnormalities observed in the NEXAVAR arm versus the placebo arm, respectively, were hypophosphatemia (45% vs 11%), anemia (44% vs 49%), elevated lipase (41% vs 30%), elevated amylase (30% vs 23%), lymphopenia (23% vs 13%), neutropenia (18% vs 10%), thrombocytopenia (12% vs 5%), hypocalcemia (12% vs 8%), and hypokalemia (5.4% vs 0.7%)
In the DTC study, the most common laboratory abnormalities observed in the NEXAVAR arm versus the placebo arm, respectively, were elevated ALT (59% vs 24%), elevated AST (54% vs 15%), and hypocalcemia (36% vs 11%).The relative increase for the following laboratory abnormalities observed in NEXAVAR-treated DTC patients as compared to placebo-treated patients is similar to that observed in the RCC and HCC studies: lipase, amylase, hypokalemia, hypophosphatemia, neutropenia, lymphopenia, anemia, and thrombocytopenia
Avoid concomitant use of strong CYP3A4 inducers, when possible, because inducers can decrease the systemic exposure of sorafenib. NEXAVAR exposure decreases when co-administered with oral neomycin. Effects of other antibiotics on NEXAVAR pharmacokinetics have not been studied
Most common adverse reactions reported for NEXAVAR-treated patients vs placebo-treated patients in unresectable HCC, respectively, were: diarrhea (55% vs 25%), fatigue (46% vs 45%), abdominal pain (31% vs 26%), weight loss (30% vs 10%), anorexia (29% vs 18%), nausea (24% vs 20%), and hand-foot skin reaction (21% vs 3%). Grade 3/4 adverse reactions were 45% vs 32%
Most common adverse reactions reported for NEXAVAR-treated patients vs placebo-treated patients in advanced RCC, respectively, were: diarrhea (43% vs 13%), rash/desquamation (40% vs 16%), fatigue (37% vs 28%), hand-foot skin reaction (30% vs 7%), alopecia (27% vs 3%), and nausea (23% vs 19%). Grade 3/4 adverse reactions were 38% vs 28%
Most common adverse reactions reported for NEXAVAR-treated patients vs placebo-treated patients in DTC, respectively, were: palmar-plantar erythrodysesthesia syndrome (PPES) (69% vs 8%), diarrhea (68% vs 15%), alopecia (67% vs 8%), weight loss (49% vs 14%), fatigue (41% vs 20%), hypertension (41% vs 12%), rash (35% vs 7%), decreased appetite (30% vs 5%), stomatitis (24% vs 3%), nausea (21% vs 12%), pruritus (20% vs 11%), and abdominal pain (20% vs 7%). Grade 3/4 adverse reactions were 65% vs 30%

For full prescribing information, visit http://labeling.bayerhealthcare.com/html/products/pi/Nexavar_PI.pdf.

About Copanlisib
Copanlisib is a pan-Class I phosphatidylinositol-3-kinase (PI3K) inhibitor with predominant inhibitory activity against PI3K-α and PI3K-δ isoforms, being developed by Bayer.

The efficacy and safety of copanlisib has not been established. The broad clinical development program for copanlisib also includes Phase III studies in indolent NHL patients who have relapsed or are refractory to prior therapies. Information about these trials can be found at www.clinicaltrials.gov and www.chronostrials.com.

The U.S. Food and Drug Administration (FDA) granted Priority Review designation for the New Drug Application (NDA) for copanlisib for the treatment of relapsed or refractory FL patients who have received at least two prior therapies in May 2017. Copanlisib has also been granted Orphan Drug Designation for the treatment of splenic, nodal, and extranodal subtypes of marginal zone lymphoma. The compound is not approved by the FDA, the European Medicines Agency or any other health authority.

About Darolutamide
Darolutamide is an investigational oral androgen receptor (AR) antagonist that is thought to block the growth of cancer cells by binding to the AR and inhibiting the receptor function. In preclinical studies, darolutamide and its main circulating metabolite were also active in known AR mutations, such as W742L and F877L.

Darolutamide is currently in Phase III clinical trials for the treatment of patients with castration-resistant prostate cancer (CRPC). It is not approved by the U.S. Food and Drug Administration, the European Medicines Agency or any other health authority.

About Anetumab Ravtansine (BAY 949343)
Anetumab ravtansine is an antibody-drug conjugate (ADC) that specifically targets mesothelin, a surface marker protein overexpressed in many cancers. After binding to mesothelin, anetumab ravtansine is taken up inside the tumor cells, where degrading enzymes release cytotoxic DM4, a maytansinoid tubulin inhibitor, which induces cell cycle arrest and apoptosis in dividing cells.

In a Phase I clinical trial in patients with advanced solid tumors, anetumab ravtansine demonstrated efficacy with durable responses in patients with malignant pleural mesothelioma (MPM), and a manageable safety profile. In addition to the Phase II clinical trial in MPM, anetumab ravtansine is currently being investigated in a variety of other mesothelin-positive tumors, including malignant pleural mesothelioma, ovarian cancer and six other types of advanced solid tumors.

Anetumab ravtansine is a compound developed by Bayer. In the development, the following collaborators were involved: The antibody was derived from the HuCAL technology platform of MorphoSys AG. In a 2008 license agreement with ImmunoGen, Inc., Bayer was granted exclusive rights for using their maytansinoid ADC technology to develop anti-tumor therapies targeting mesothelin. Both partners are entitled to milestone payments and royalties on commercial sales, if any.

About Rogaratinib
Rogaratinib (BAY 1163877) is an oral, small molecule pan-fibroblast growth factor receptor (FGFR) inhibitor of FGFRs 1-4 with antineoplastic activity demonstrated in preclinical studies. Rogaratinib is currently being investigated in patients with advanced solid tumors with high FGFR mRNA expression (NCT01976741). The compound is not approved by the U.S. Food and Drug Administration, the European Medicines Agency or any other health authority.

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now includes three oncology products and several other compounds in various stages of clinical development. Together, these products reflect the company's approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

Bayer: Science For A Better Life
Bayer is a global enterprise with core competencies in the Life Science fields of health care and agriculture. Its products and services are designed to benefit people and improve their quality of life. At the same time, the Group aims to create value through innovation, growth and high earning power. Bayer is committed to the principles of sustainable development and to its social and ethical responsibilities as a corporate citizen. In fiscal 2016, the Group employed around 115,200 people and had sales of EUR 46.8 billion. Capital expenditures amounted to EUR 2.6 billion, R&D expenses to EUR 4.7 billion. These figures include those for the high-tech polymers business, which was floated on the stock market as an independent company named Covestro on October 6, 2015. For more information, go to www.bayer.us.

Forward-Looking Statement
This news release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

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