Cancer Therapy Update in 2017

Transcription

1 Cancer Therapy Update in 2017 Editor: Le Wang, M.D., Ph.D Medical Oncology and Hematology (Board-Certified) Ibrutinib (Imbruvica) Pharmacyclics 1 /19/2017 Lymphoma Marginal Zone Lymphoma (MZL), Relapsed/Refractory Approved for the treatment of patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti CD20-based therapy. Dosing: Ibrutinib, 500mg, PO, daily Marginal zone lymphoma accounts for approximately 12% of non-hodgkin lymphoma in adults, including three subtypes: mucosa-associated, nodal, and splenic marginal zone lymphoma. The approval covers all three subtypes of marginal zone lymphoma. The overall response rate was 46%, in which 3.2% had complete response and 42.9% had a partial response.. The median time to response was 4.5 months and the median duration of the response was not yet reached at the time of this approval. Previously, the Ibrutinib was approved for chronic lymphocytic leukemia with 17p deletion, mantle cell lymphoma and waldenstrom macroglobulinemia. Tel: ; Fax: Page 1 of 28

2 Nivolumab (Opdivo) Bristol-Myers Squibb 2 /2 /2017 Genitourinary (GU) Cancers Urothelial carcinoma, locally advanced or metastatic Approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma (bladder cancer) who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum - containing chemotherapy. Dosing: Nivolumab 240 mg, IV over 60 minutes every two weeks until disease progression or unacceptable toxicity. Bladder cancer is the fifth most diagnosed cancer. The majority of bladder cancers are diagnosed at an early stage, but approximately 50-70% of patients will experience a recurrence within five years after the first line therapy. Therefore, the poor durability of the response after the initial therapy as well as lack of effective second line therapy present a major challenge in the treatment of recurrent or metastatic disease. Treatment with Opdivo resulted in an approximately 20% overal response across all levels of PD-L1 expression ( 1% vs. <1%). Tel: ; Fax: Page 2 of 28

3 Lenalidomide (Revlimid) Celgene 2 /22/2017 Plasma Cell Disorders Multiple myeloma Revlimid 10-mg capsules approved for patients with multiple myeloma as maintenance therapy after autologous stem cell transplant. Dosing: Lenalidomide, 10mg, daily until disease progression or unacceptable toxicity. Autologous stem cell transplantation after induction therapy remains the integral part of the standard care for transplant eligible multiple myeloma. However, most patients will still see their disease recurrence or progression after the transplant. Lenalidomide maintenance therapy prolongs disease-recurrence free survival after autologous stem cell from 1.9 years to 5.7 years. Ribociclib (Kisqali) Novartis 3 /13/2017 Breast Cancer Breast Cancer, ER/PR-positive, Her2-negative Approved in combination with aromatase inhibitor as an initial endocrinebased therapy for the treatment of postmenopausal woman with advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. Dosing: Ribociclib, 600mg, po, daily, 3 weeks, 1 week off, with four weeks of any aromatase inhibitor. This is the second CDK 4/6 inhibitor approved for postmenopausal woman with ER/PR-positive and Her2-negative metastatic breast cancer. Ribociclib plus letrozole reduced the risk of disease progression or death by 44% compared to letrozole alone. More than half of the patient's taking the combination had experienced tumor burden reduction by at least 30%. This combination is now a new standard care for initial treatment of HR-positive advanced breast cancer. Tel: ; Fax: Page 3 of 28

4 Pembrolizumab (Keytruda) Merck 3 /15/2017 Lymphoma Hodgkin's lymphoma, refractory Approved for the treatment of adults with refractory classical Hodgkin's lymphoma and for those who have relapsed after three or more prior lines of therapy. Dosing: Keytruda, 200 mg, every three weeks acute disease progression or unacceptable toxicity. The approval also includes patient who had received autologous stem cell transplantation or had received Adcetris (brentuximab vedotin). The overall response rate (ORR) with Keytruda was 69%, including complete responses in 22% of patients and partial responses in 47% of patients. The median duration of response was 11.1 months. Avelumab (Bavencio) Pfizer Inc 3 /23/2017 Skin Cancers Merkel cell carcinoma (MCC), metastatic Approved for the treatment of patients 12 years and older with metastatic Merkel cell carcinoma, including those who have not received prior chemotherapy. Dosing: Avelumab, 10 mg/kg, IV, every 2 weeks. Merkel cell carcinoma (MCC) is a rare and the most aggressive form of skin cancer. The mortality rate is very high with fewer than half of patients survived more than one year. Avelumab blocks the PD-1/PD-L1 pathway and is the first immuno checkpoint inhibitor approved for the treatment of this type of cancer. 11% of patients experienced a complete response and 33% experienced partial response. The response lasted for more than 6 months in 86% of responders and more than 12 months in 45% of responders. Tel: ; Fax: Page 4 of 28

5 Niraparib (Zejula) Tesaro, Inc 3 /27/2017 Gynecological (GYN) Cancers Ovarian cancers, recurrent Approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have achieved complete or partial response to platinum-based chemotherapy. Dosing: niraparib, 300 mg orally daily Niraparib is an oral poly ADP-ribose polymerase (PARP) inhibitor that blocks enzymes involved in the repair of the damaged DNA. In the presence of PARP inhibition, the damaged DNA in cancer cells (not in normal cells) is unable to be repaired, therefore leading to the death or inhibition of cancer cells. Niraparib is approved for this indication regardless of the tumor's BRCA status. However, in the patients with BRCA mutation, the median PFS with niraparib was 21 months compared with 5.5 months with placebos (HR of 0.27), whereas in the patients without BRCA mutation, the median PFS was 9.3 months with niraparib and 3.9 months with placebo (HR of 0.45). Tel: ; Fax: Page 5 of 28

6 Palbociclib (Ibrance) Pfizer Inc 3 /31/2017 Breast Cancer Breast cancer, ER/PR-positive, Her2-negative Approved for the treatment of advanced or metastatic hormone receptorpositive, Her2-negative breast cancer in combination with any aromatase inhibitor as initial endocrine based therapy in postmenopausal women. Dosing: Palbociclib 125 mg, orally daily for 21 consecutive days, followed by 7 days off, in combination with Letrozole 2.5 mg orally daily. Ibrance was initially approved in February 2015 in combination with letrozole for the treatment of ER positive and HER2-negative advanced breast cancer for postmenopausal woman as a new standard of initial therapy. This approval extends the use of any aromatase inhibitor including Letrozole and Anastrozole in combination with Ibrance for this indication. In February 2016, FDA also granted the use of Ibrance with Letrozol as a second line treatment for ER positive and Her2 negative advanced breast cancer. Atezolizumab (Tecentriq) Genentech, Inc 4 /17/2017 Genitourinary (GU) Cancers Bladder cancer, advanced Approved for the treatment of advanced or metastatic bladder cancer as initial therapy in patients who are not eligible for cisplatin chemotherapy. Dosing: Atezolizumab, 1200 mg, IV, every 21-day cycle Atezolizumab is PD-L1 inhibitor and was initially approved for the treatment of the advanced refractory bladder cancer in May 2016 in patients who had received platinumbased chemotherapy. The new approval grants its use in frail patients who otherwise do not have good treatment options. In this group of patients, the overall response rate was 23.5%, in which 6.7% had a complete response and 16.8% had a partial response. Tel: ; Fax: Page 6 of 28

7 Regorafinib (Stivaga) Bayer 4 /27/2017 Gastrointestinal (GI) Cancers Hepatocellular carcinoma (HCC), refractory Approved for the treatment of patients with hepatocellular carcinoma who have previous treated with drugs sorafenib. Dosing: Regorafenib, 160 mg, PO, daily This is the first FDA approved treatment for almost a decade to treat hepatocellular carcinoma as a second line after sorafenib. Regorafinib is a kinase inhibitor that works by blocking several enzymes that promote cancer growth. It is the first and only treatment to demonstrate significant improvement in overall survival in second-line HCC patients. Midostaurin (Rydapt) Novartis 4 /28/2017 Leukemia Acute myeloid leukemia, FLT3 mutation Approved for the treatment of adult patients with newly diagnosed acute myeloid leukemia who have FLT3 mutation as detected by an FDA approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consultation. Dosing: Midostaurin, 50 mg PO BID (~q12hr) on Days 8-21 of each cycle of induction with cytarabine and daunorubicin and on Days 8-21 of each cycle of consolidation with high-dose cytarabine. This new approval establishes a new standard care for high risk patients with acute myeloid leukemia. Approximately one third of acute myeloid leukemia patients have FLT3 gene mutation which often result in faster disease progression, higher relapse rate and lower rates of survival compared to other forms of acute myeloid leukemia. The clinical trial demonstrated a significant improvement in overall survival with 23% reduction in the risk of death (HR 0.77). Tel: ; Fax: Page 7 of 28

8 Brigatinib (Alunbrig) Takeda Pharmaceutical 4 /28/2017 Lung Cancers Non-small cell lung cancers, ALK-positive Approved for the treatment of patients with metastasis ALK-positive non-small cell lung cancer who have progressed on or are intolerant to crizotinib. Dosing: ALUNBRIG, 90 mg, PO, daily for the first 7 days. If 90 mg is tolerated during the first 7 days, then increase the dose to 180 mg orally once daily. Brigatinib is one of the small molecule ALK inhibitors. It overcomes mechanism of chemical resistance to crizotinib including progression in the central nervous system. The overall response rate was approximately 50%. The median duration of response was 13.8 months. For patients who had measurable brain metastasis, the intracranial overall response rate ranged from 42% to 67%. Durvalumab (Imfinzi) AstraZeneca 5 /1 /2017 Genitourinary (GU) Cancers Urothelial carcinoma, advanced or metastatic Approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma (bladder cancer) who have disease progression during or following platinum-containing chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinumcontaining chemotherapy. Dosing: Durvalumab, 10 mg/kg, IV, every two weeks until disease progression or unacceptable toxicity. Durvalumab is a PD-L1 inhibitor. Testing for PD-L1 expression on tumor cells, however, is not required for use of this drug. The overall objective response rate was 17% in all patients. In patients with high PD-L1 expression, the objective response rate was 26.3%. In patients with low/negative PD-L1 expression, the response rate was 4.1%. Tel: ; Fax: Page 8 of 28

9 Avelumab (Bavencio) Pfizer Inc 5 /9 /2017 Genitourinary (GU) Cancers Urothelial carcinoma, advanced or metastatic Approved for patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinumcontaining chemotherapy. Dosing: Avelumab, 10 mg/kg, every two weeks, until diseaseis progression or unacceptable toxicity. This is the third immunotherapy approved for advanced or metastatic bladder cancer (2nd line) after atezolizumab (1st line) and durvalumab (2nd line). Avelumab was also approved for the treatment of Merkel cell carcinoma. Tel: ; Fax: Page 9 of 28

10 Pembrolizumab (Keytruda) Merck 5 /10/2017 Lung Cancers Non-squamous non-small cell lung cancer, untreated metastatic Pembrolizumab in combination with pemetrexed and carboplatin for the treatment of patients with previously untreated non-squamous non-small cell lung cancer. Dosing: Pembrolizumab, 200 mg, IV, every 3 weeks, in combination with pemetrexed and carboplatin (PC) for 4 cycles followed by pembrolizumab for a maximum of 24 months. This is a practice changing milestone. Pembrolizumab is the first PD-L1 inhibitor approved in the first line setting in combination with chemotherapy for patients with metastatic non-squamous cell non-small cell lung cancer irrespective of PD-L1 expression level. The overall response rate was 55% in patients who received Pembrolizumab plus chemotherapy versus 29% in those who received chemotherapy alone. The median progression free survival was 13 months with Pembrolizumab versus 8.9 months for chemotherapy alone (HR of 0.53). Previously, Pembrolizumab was approved in the first line setting as a single agent over chemotherapy when PD-L1 expression on tumor cells is above 50%. Tel: ; Fax: Page 10 of 28

11 Pembrolizumab (Keytruda) Merck 5 /18/2017 Genitourinary (GU) Cancers Urothelial carcinoma, metastatic Approved for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Also granted accelerated approval as first-line therapy for patients who cannot receive standard chemotherapy containing platinum (cisplatin) on 5/22/2017. Dosing: Pembrolizumab, 200 mg, IV, every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. Keytruda is the only PD-L1 blocker in second line setting that showed overall survival benefit versus chemotherapy in phase 3 studies. It is now also available for use as a firstline treatment option for patients with advanced urothelial bladder cancer who are not eligible for the standard of care, cisplatin-based chemotherapy. Tel: ; Fax: Page 11 of 28

12 Pembrolizumab (Keytruda) Merck 5 /23/2017 Tissue/site-agnostic approval MSI-H solid tumors Approved for patients with unresectable or metastatic, microsatellite instability high (MSI-H) or mismatch repair deficient (dmmr) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. Dosing: pembrolizumab, 200 mg, IV q 3 weeks, or 10 mg/kg, q 2 weeks, until unacceptable toxicity, or disease progression. Until now, the cancer treatments are largely based on where in the body the cancer is originated. This approval marks an important step that cancer treatment can also be based on a common biomarker rather than the location or histology of the tumor itself. Ceritinib (Zykadia) Novartis 5 /26/2017 Lung Cancers Non-small cell lung cancers, ALK-positive Approved for patients with anaplastic lymphoma kinase (ALK)-positive metastatic non small cell lung cancer (NSCLC) (1st or 2nd line). Dosing: Ceritinib 750 mg, PO, daily until disease progression. In April 2014, ceritinib was first approval as second line tretment for patients with ALKpositive metastatic NSCLC whose disease has progressed or who are intolerant to crizotinib. The new approval grants the use of ceritinib as a first-line treatment for ALKpositive non-small cell lung cancer. Tel: ; Fax: Page 12 of 28

13 Daratumumab (Darzalex) Janssen 6 /16/2017 Plasma Cell Disorders Multiple myeloma, relapsed or refractory Dartumumab in combination with pomalidomide (Pomalyst) and dexamethasone approved for the treatment of patients with multiple myeloma who have received at least two prior therapies including lenalidomide (Revlimid) and proteasome inhibitor. Dosing: Daratumumab (16 mg/kg) in combination with pomalidomide and dexamethasone. Daratumumab targets the CD38 protein. Daratumumab was previously approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone (3rd line) to treat patients who have received at least one prior medicine to treat multiple myeloma; and alone in patients who have received at least three prior medicines to treat multiple myeloma, including a proteasome inhibitor and an immunomodulatory agent, or did not respond to a proteasome inhibitor and an immunomodulatory agent. Tel: ; Fax: Page 13 of 28

14 Dabrafenib (Tafinlar)/Trametinib (Mekinist) Combination GlaxoSmithKline (GSK) 6 /22/2017 Lung Cancers Non-small cell lung cancer, metastatic with BRAF V600 E mutation The combination approved for the treatment of patients with metastatic nonsmall cell lung cancer positive for BRAF V600E mutation. Regimen: Dabrafenib, 150 mg, PO, Bid/Trametinib, 2 mg, PO, daily. BRAF mutation appears in approximately 1 to 3% of non-small cell lung cancer cases. This approval makes the BRAF mutation the 4th actionable genomic biomarker in metastasis non-small cell lung cancer. The three others are EGFR, ALK and ROS1. This approval is for the combination to use both first-line and second line settings. The overall response rate was 61%. In the second line setting, the overall response rate was 63%. Panitumumab (Vectibix) Amgen 7 /10/2017 Gastrointestinal (GI) Cancers Colorectal cancers, metastatic Approved for patients with wild-type KRAS and NRAS metastatic colorectal cancer as first-line therapy in combination with FOLFOX. Regimen: Panitumumab, 6 mg/kg, IV, every 14 days, in combination with standard FOLFOX. Panitumumab is the first fully humanized monoclonal anti epidermal growth factor receptor (EGFR) antibody approved by FDA for use in combination with FOLFOX in the 1st line setting for patients with wild-type RAS (defined as wild-type in both KRAS and NRAS) metastatic colorectal cancer (mcrc). Previously, the drug was approved as monotherapy following disease progression after prior treatment with FOLFOX or FOLFIRI. Tel: ; Fax: Page 14 of 28

15 Nivolumab (Opdivo) Bristol-Myers Squibb 7 /31/2017 Gastrointestinal (GI) Cancers Metastatic colorectal cancer, MSI-high Approved for the treatment of adult patients with MSI high or mismatch repair deficient metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Dosing: Nivolumab 3 mg/kg, IV, q 2 weeks until unacceptable toxicity or radiographic progression. The approval was based on the overall response rate (28%) and duration of response (>6 month in 67% of patients). The opdivo has not been approved for use in other tumor types with MSH-high at this time. Enasidenib (Idhifa) Celgene 8 /1 /2017 Leukemia Acute myeloid leukemia, IDH2 mutant, relapsed or refractory Approved for the treatment of adult patients with relapsed or refractory AML carrying IDH2 mutation. Dosing: Enasidenib, PO, daily Enasidenib (Idhifa) is the first oral targeted therapy for adult patients with relapsed/refractory acute myeloid leukemia and an IDH2 Mutation. For 8 to 19% AML patients, the mutated IDH2 enzyme blocks normal blood cell development and results in an overabundance of immature blood cells. Idhifa is an isocitrate dehydrogenase-2 inhibitor. Tel: ; Fax: Page 15 of 28

16 Ibrutinib (Imbruvica) Pharmacyclics 8 /2 /2017 Stem Cell Transplantation Chronic graft-vs-host disease Approved for the treatment of adult patients with chronic graft-vs-host disease after failure of one or more lines of systemic therapy. Dosing: Ibrutinib, 420mg, PO daily This is the first FDA-approved therapy for the treatment of chronic graft-vs-host disease. Daunorubicin/Cytarabine (Vyxeos) Jazz Pharmaceuticals 8 /3 /2017 Leukemia Acute myeloid leukemia (AML) Approved for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia (t-aml) or AML with myelodysplasia-related changes (AML-MRC). Regimen: Liposome-encapsulated daunorubicin-cytarabine Combination. This is the first FDA-approved treatment specifically for patients with therapy-related AML or AML with myelodysplasia-related changes, two types of AML with a poor prognosis. Tel: ; Fax: Page 16 of 28

17 Olaparib (Lynparza) AstraZeneca 8 /17/2017 Gynecological (GYN) Cancers Ovarian cancer Approved for the maintenance therapy in adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have achieved complete or partial response to platinum-based chemotherapy irrespective of their BRCA mutation status. Dosing for maintenance: Olaparib, 300mg, PO, Bid Olaparib capsules was approvd in 2014 for the treatment of patients with BRCAmutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Olaparib tablets and capsules are not interchangeable. Olaparib capsules are being phased out of the U.S. market. Tel: ; Fax: Page 17 of 28

18 Tisagenlecleucel (Kymriah) Novartis 8 /30/2017 Leukemia B-cell precursor acute lymphoblastic leukemia (ALL) Approved for pediatric and young adult patients up to 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) refractory to initial treatment or in second or later relapse. Dosing: Each dose of tisagenlecleucel is created using an individual patient s own T cells, which are collected and genetically modified to include a new gene that contains a chimeric antigen receptor (CAR) protein. Once the cells are modified, they are infused back into the patient, where the genetically modified CAR T cells are able to target and kill leukemia cells that have a CD19 antigen on the surface. Tisagenlecleucel is a genetically modified autologous T-cell immunotherapy. One of the life-threatening side effect of CAR-T therapy is the cytokine release syndrome. Fortunately, on the same day, the FDA also expanded the approval of tocilizumab (Actemra) to treat CAR T-cell induced severe or life-threatening cytokine-release syndrome. CAR-T therapy is currently only approved for use in designated hospital. Bevacizumab-awwb (Mvasi) Amgen 9 /14/2017 Clinical Pharmacology Multi-Solid Cancers Approved as a biosimilar to bevacizumab (Avastin) for the treatment of multiple types of cancer. Dosing: similar as avastin according to the tumor types. First biosimilar approved in the U.S. for the treatment of multiple cancers, including metastatic colon cancer, NSCLC, RCC, cervical cancers and glioblastoma who have progressed on previous therapies. Bevacizumab was approved to Genetech in February They are not interchangeable. Tel: ; Fax: Page 18 of 28

19 Cabazitaxel (Jevtana) Sanofi-Aventis 9 /14/2017 Genitourinary (GU) Cancers Prostate cancer, castration-resistant A lower dose of cabazitaxel (20 mg/m2 every 3 weeks) (JEVTANA, Sanofi- Aventis) in combination with prednisone approved for the treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen. Cabazitaxel (25 mg/m2 every 3 weeks) was approved for this indication in Copanlisib (Aliqopa) Bayer 9 /14/2017 Lymphoma Follicular lymphoma, relapsed Approved for adults with relapsed follicular lymphoma who have received at least two prior systematic therapies. Dosing: Copanlisib, 60mg, IV, on days 1, 8, and 15 of a 28-day treatment cycle until disease progression or unacceptable toxicity. Copanlisib is the multi-kinase inhibitor that works by blocking several enzymes that promote cell growth. The approval was based on single arm phase 2 trial, in which the overall response rate was 59% with 14% of those achieving complete response. The median duration of response was 12.2 months. This drug is also approved for the treatment of patients with marginal zone lymphoma. Tel: ; Fax: Page 19 of 28

20 Pembrolizumab (Keytruda) Merck 9 /22/2017 Gastrointestinal (GI) Cancers Recurrent gastric or GE junction adenocarcinoma Approved for patients with recurrent locally advanced or metastatic, gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 and have progressed on or after two or more prior systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy. Approved dose: 200mg, q 3 weeks This is generally used as a third line therapy. PD-L1 positivity is defined as a combined positive score (CPS) 1. CPS is determined by the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by total number of tumor cells evaluated, multiplied by 100. Although the objective response rate was only 13.3%, the duration response can range somewhat from 2.8 months to 19.4 months. Nivolumab (Opdivo) Bristol-Myers Squibb 9 /22/2017 Gastrointestinal (GI) Cancers Hepatocellular Carcinoma (HCC) Approved for the treatment of hepatocellular carcinoma in patients who have progressed on sorafenib. Approved dose: 3 mg/kg, q 2 weeks. Sarafenib has been the only treatment for the advanced HCC for the last 10 years. This approval marks the first immunotherapy approved as a second line treatment for patients with HCC progressed on sorafenib. Early this year (April 27, 2017), FDA approved Stivaga to treat HCC after sorafenib. Tel: ; Fax: Page 20 of 28

21 Abemaciclib (Verzenio) Eli Lilly and Company 9 /28/2017 Breast Cancer Breast cancer, metastatic, HR-positive, Her2-negative 1) Abemaciclib in combination with fulvestrant approved for woman with HR positive, Her2 negative advanced or metastatic breast cancer with disease progression following initial endocrine therapy. Dosing: 150mg, PO Bid, in combination with fulvestrant. 2) Abemaciclib approved as monotherapy for woman and men with HR positive, Her2 negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. Dosing: 200mg twice daily This is the third CDK 4/6 inhibitor approved for the treatment of HR-positive and Her2- negative metastatic breast cancer. The other two are palbociclib in February 2015 and ribociclib in March However, the later two were not approved as monotherapy. Axicabtagene ciloleucel (Yescarta) Kite Pharma, Inc 10/18/2017 Lymphoma Large B-cell lymphoma, relapsed or refractory Axicabtagene ciloleucel is a chimeric antigen receptor (CAR) T-cell therapy approved to treat adult patients with relapsed or refractory large B cell lymphoma of to two or more lines all systematic therapies. The approved diseases include diffuse large B cell lymphoma, primary mediastinal large B cell lymphoma, high-grade B-cell lymphoma, and diffuse large B cell lymphoma arising from follicular lymphoma. This is first CAR-T therapy approved by FDA for the treatment of adult malignancies. However, its potential severe toxicity limits its use in academic centers at the present time. Tel: ; Fax: Page 21 of 28

22 Acalabrutinib (Calquence) AstraZeneca 10/31/2017 Lymphoma Mantle cell lymphoma (MCL) Approved for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Dose: Acalabrutinib, 100-mg, PO Bid, until disease progression or unacceptable toxicity. Acalabrutinib is a Bruton tyrosine kinase (BTK) inhibitor. This is the second Bruton kinase inhibitor approved by FDA to treat lymphoma. Mental cell lymphoma is a rare and aggressive type of lymphoma, accounting approximately 3 to 10% of all non- Hodgkin's lymphoma cases in the United States. Vemurafenib (Zelboraf) Genentech, Inc 11/6 /2017 Myeloid Disorders Erdheim-Chester Disease (ECD) with BRAF V600 mutation Approved for the treatment of patients with Erdheim-Chester Disease (ECD) with BRAF V600 mutation. Dosing: Vemurafenib, 960 mg, PO, Bid with or without a meal. Erdheim-Chester Disease (ECD), also known as polyostotic sclerosing histiocytosis, is a rare disease characterized by the abnormal multiplication of a specific type of white blood cells called histiocytes, or tissue macrophages. Therefore, this disease is also called a non-langerhans-cell histiocytosis. The disease involves an infiltration of lipidladen macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, resulting in a generalized sclerosis of the long bones. Bone pain is the most common symptoms. Exophthalmos occurs in some patients several years before the disease onset and is usually bilateral, symmetric and painless. Tel: ; Fax: Page 22 of 28

23 Alectinib (Alecensa) Genentech, Inc 11/6 /2017 Lung Cancers ALK-positive metastatic non-small cell lung cancer (NSCLC) Approved for treatment of patients with anaplastic lymphoma kinase (ALK)- positive metastatic non-small cell lung cancer (NSCLC), as detected by an FDAapproved test, as initial therapy. Dosing: Alectinib, 600 mg, PO, Bid, with food In December 2015, alectinib received accelerated approval for treatment of patients with ALK-positive metastatic NSCLC whose disease progressed on or who were intolerant of crizotinib. This approval markes the alectinib as a new first-line treatment and superior to crizotinib for the treatment of ALK-positive non-small cell lung cancer. Brentuximab vedotin (Adcetris) Seattle Genetics 11/9 /2017 Lymphoma Primary cutaneous anaplastic large cell lymphoma (pcalcl) Approved for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcalcl) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy. Dosing: Brentuximab vedotin, 1.8 mg/kg (max 180 mg), IV, q 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity. This approval establishes Adcetris as the new standard of care for CD 30 expressing lymphoma. Brentuximab is an antibody conjugate that targets CD30 on the surface of most classical Hortons lymphoma cells and in several types of non-hodgkin's lymphoma, but on healthy cells. Tel: ; Fax: Page 23 of 28

24 Abemaciclib (Verzenio) Eli Lilly and Company 11/15/2017 Breast Cancer Advanced Breast Cancer, ER positive, Her2-negative Fulvestrant (Faslodex), combined with abemaciclib (Verzenio), also approved in Europe for the treatment of ER positive, Her2-negative advanced or metastatic breast cancer in women whose diseases have progressed on previous endocrine therapy. Dosing: Fulvestrant, 500 mg IM, monthly, plus abemaciclib 150 mg PO, Bid. Abemaciclib (Verzenio) is a cyclin-dependent kinase (CDK) 4/6 inhibitor. Fulvestrant was also approved for use in combination with another CDK4/6 inhibitor palbociclib (Ibrance) for ER positive, Her2-negative locally advanced or metastatic breast cancer in women who have received prior endocrine therapy. Sunitinib malate (Sutent) Pfizer Inc 11/16/2017 Genitourinary (GU) Cancers Kidney Cancer Approved for the adjuvant treatment of patients with high risk renal cell carcinoma following nephrectomy. Dosing: Sutent, 50 mg, PO, daily, with or without food, 4 weeks 2 weeks off for 9 cycles. This is the first TKI ever approved for adjuvant therapy for high risk RCC after nephrectomy. Tel: ; Fax: Page 24 of 28

25 Obinutuzumab (Gazyva) Genentech, Inc 11/17/2017 Lymphoma Follicular lymphoma, 1st line Obinutuzumab approved in combination with chemotherapy, followed by obinutuzumab monotherapy as maintenance, for the treatment of patients with previously untreated stage II bulky, III, or IV follicular lymphoma (FL). Dosing: Obinutuzumab, 1000 mg, IV, days 1, 8 and 15 of cycle 1; 1000 mg, day 1 of cycles 2-6 or cycles 2-8; and then 1000 mg, q 2 months for up to 2 years. The chemotherapy backbone can be either bendamustine, CHOP or CVP. Trastuzumab-dkst (Ogivri) Mylan GmbH 12/1 /2017 Breast Cancer Breast cancer, or metastatic gastric/esophageal cancers Approved as a biosimilar to trastuzumab (Herceptin) for the treatment of patients with Her2-positive -breast or metastatic gastric/gastroesophageal junction adenocarcinoma. Trastuzumab-dkst was approved as a biosimilar, but not as an interchangeable product to herceptin. Tel: ; Fax: Page 25 of 28

26 Cabozantinib (Carbometyx) Exelixis, Inc 12/19/2017 Genitourinary (GU) Cancers Renal cell carcinoma Approved for the treatment of patients with advanced renal cell carcinoma in the first line setting. Dosing: Cabometyx, 60mg, orally daily until disease progression or unacceptable toxicity. Cabometyx previously approved in 2016 for treatment of patients with advanced RCC who have received prior anti-angiogenic therapy. Today's approval leads to the use of Cabometyx in the first line setting and superior to sunitinib. Cabozantinib is also approved for the treatment of medullary thyroid cancer but is marketed under the trade name Cometriq. Please note that Cometriq and Cabometyx are not interchangeable because of their different formulations. Bosutinib (Bosulif) Pfizer Inc 12/19/2017 Leukemia Chronic myelogenous leukemia Approved for treatment of patients with newly-diagnosed chronic phase (CP) Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML). Dosing: Bosutinib 400 mg once daily with food FDA first approved bosutinib in 2012 for treatment of patients with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy. Tel: ; Fax: Page 26 of 28

27 Pertuzumab (Perjeta) Genentech, Inc 12/20/2017 Breast Cancer Breast cancer, adjuvant treatment Approved for use in combination with trastuzumab (Herceptin) and chemotherapy as adjuvant treatment for patients with Her2-positive early breast cancer at high risk of recurrence. Regimen: 6 to 8 cycles of chemotherapy with pertuzumab and trastuzumab, followed by pertuzumab and trastuzumab alone every 3 weeks for a total of 1 year of therapy. Previously, pertuzumab was approved for use in combination with trastuzumab and docetaxel to treat Her2-positive breast cancer in both first line metastatic setting (2012) and neoadjuvant setting (2013). With this approval, the pertuzumab now can be used in adjuvant sitting for high risk Her2-positive early breast cancer (>2cm, HR-negative or node-positive). Nivolumab (Opdivo) Bristol-Myers Squibb 12/21/2017 Skin Cancers Melanoma Approved for the adjuvant treatment of patients with melanoma with involvement of lymph nodes, or in patients with metastatic disease who have undergone complete resection. Dosing (adjuvant): nivolumab, 240 mg, IV every two weeks until disease progression or unacceptable toxicity, for a maximum of one year. Nivolumab was previously approved for the treatment of patients with unresectable or metastatic melanoma. This approval leads to nivolumab as a new adjuvant treatment option for patients with completely resected myeloma. Tel: ; Fax: Page 27 of 28

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