Understanding Cancer FDA Updates

Recent Approvals from the U.S. Food and Drug Administration

Cabometyx Approved to Treat Hepatocellular Carcinoma
The U.S. Food and Drug Administration has approved Cabometyx (cabozantinib) tablets for people with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 

The FDA’s approval of Cabometyx was based on results from a phase III trial of Cabometyx for people with advanced hepatocellular carcinoma who received prior sorafenib. The results showed that Cabometyx demonstrated a statistically significant and clinically meaningful improvement in overall survival versus placebo. Cabometyx, which is a kinase inhibitor marketed by Exelixis, is also approved for the treatment of people with advanced renal cell carcinoma.

FDA Approves Keytruda for Adjuvant Treatment of Melanoma
Keytruda (pembrolizumab) has been granted FDA approval for the adjuvant treatment of people with melanoma with involvement of lymph nodes following complete resection. In a phase III trial, Keytruda – an anti-PD-1 therapy marketed by Merck – significantly prolonged recurrence-free survival, reducing the risk of disease recurrence or death by 43 percent compared to placebo in people with resected, high-risk stage III melanoma. 

Lonsurf Gains FDA Approval for Recurrent, Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma
The FDA has approved Taiho’s Lonsurf (trifluridine/tipiracil) as a treatment for adults with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy. Lonsurf tablets are a fixed combination of trifluridine, which is a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor. 

The approval for Lonsurf follows an FDA Priority Review designation and is based on data from a phase III trial evaluating Lonsurf plus best supportive care versus placebo plus best supportive care in people with previously treated advanced gastric cancer or GEJ adenocarcinoma following progression or intolerance to previous lines of standard therapy. The trial met its primary and secondary endpoints demonstrating prolonged overall survival with Lonsurf versus placebo.

FDA Approves New Formulation of Herceptin for Injection
Genentech’s Herceptin Hylecta (trastuzumab and hyaluronidase-oysk injection) has been approved by the FDA for subcutaneous (under the skin) injection for the treatment of HER2‑overexpressing breast cancer. This new treatment includes the same monoclonal antibody as intravenous Herceptin (trastuzumab) in combination with recombinant human hyaluronidase PH20, an enzyme that helps to deliver trastuzumab under the skin. Herceptin Hylecta is a ready-to-use formulation that can be administered in two to five minutes, compared to 30 to 90 minutes for intravenous Herceptin.

New Drug Regimen for Acute Lymphoblastic Leukemia Gains FDA Approval
The FDA has approved Servier Pharmaceuticals’ Asparlas (calaspargase pegol-mknl) – an asparagine specific enzyme – as a component of a chemotherapy regimen to treat acute lymphoblastic leukemia (ALL) in young adults and children ages 1 month to 21 years. This new product provides for a longer interval between doses compared to other available pegaspargase products.

Lynparza Approved as First-Line Maintenance Treatment for BRCA-Mutated Advanced Ovarian Cancer

The U.S. Food and Drug Administration has approved AstraZeneca’s Lynparza (olaparib) for the maintenance treatment of adults with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. People with germline BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer should be selected for therapy based on an FDA-approved companion diagnostic. The FDA also approved the BRACAnalysis CDx test, which is manufactured by Myriad Genetic Laboratories, to identify people who are eligible for Lynparza. 

Tecentriq in Combination Approved as First-Line Treatment of Metastatic Non-Squamous Non-Small Cell Lung Cancer 
The FDA has approved Genentech’s Tecentriq (atezolizumab), in combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment of people with metastatic non-squamous, non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations. Tecentriq, a programmed death-ligand 1 (PD-L1) blocking antibody, is also approved for the treatment of people with metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy. 

FDA Approves New Treatment for Adults with Relapsed or Refractory Acute Myeloid Leukemia with a Certain Genetic Mutation
The FDA has approved Astellas Pharma’s Xospata (gilteritinib) tablets for the treatment of adults who have relapsed or refractory acute myeloid leukemia with a FLT3 mutation as detected by an FDA-approved test. The FDA also approved an expanded indication for a companion diagnostic to be used with Xospata. The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, is used to detect the FLT3 mutation in people with AML.

“Approximately 25 to 30 percent of patients with AML have a mutation in the FLT3 gene. These mutations are associated with a particularly aggressive form of the disease and a higher risk of relapse,” says Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Xospata targets this gene and is the first drug to be approved that can be used alone in treating patients with AML having a FLT3 mutation who have relapsed or who don’t respond to initial treatment.”

FDA Approves Oncology Drug That Targets a Key Genetic Driver of Cancer, Rather Than a Specific Type of Tumor
The FDA has granted accelerated approval to Vitrakvi (larotrectinib), a treatment for adult and pediatric cancer survivors whose cancers have a specific genetic feature, or biomarker. This is the second time the agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than the location in the body where the tumor originated. The approval marks a new paradigm in the development of cancer drugs that are “tissue agnostic.” 

Vitrakvi, which is manufactured by Loxo Oncology, is indicated for the treatment of adult and pediatric cancer survivors with solid tumors that have a neurotrophic receptor tyrosine kinase gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.

“[This] approval marks another step in an important shift toward treating cancers based on their tumor genetics rather than their site of origin in the body,” says FDA Commissioner Scott Gottlieb, MD. “This new site-agnostic oncology therapy isn’t specific to a cancer arising in a particular body organ, such as breast or colon cancer. Its approval reflects advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine. We now have the ability to make sure that the right patients get the right treatment at the right time.” 

New AML Treatment Gains FDA Approval
The FDA has approved Pfizer’s Daurismo (glasdegib) tablets to be used in combination with low-dose cytarabine, a type of chemotherapy, for the treatment of newly-diagnosed acute myeloid leukemia in adults who are 75 years of age or older or who have other chronic health conditions or diseases that may preclude the use of intensive chemotherapy. Almost half of the adults diagnosed with AML are not treated with intensive chemotherapy because of comorbidities and chemotherapy-related toxicities.

Venclexta in Combination Approved as AML Treatment 
Venclexta (venetoclax), in combination with azacitidine or decitabine or low-dose cytarabine, has been granted accelerated approval for the treatment of newly-diagnosed acute myeloid leukemia in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. Since this indication for Venclexta, which is marketed by AbbVie Inc. and Genentech, is approved under accelerated approval, further studies are required for continued approval. 

First Biosimilar for Treatment of Adults with Non-Hodgkin Lymphoma Gains FDA Approval
Truxima (rituximab-abbs) has been granted FDA approval as the first biosimilar to Genentech’s Rituxan (rituximab) for the treatment of adults with CD20-positive, B-cell non-Hodgkin lymphoma. It is to be used as a single agent or in combination with chemotherapy. Truxima, which is manufactured by Celltrion, is the first biosimilar to be approved in the U.S. for the treatment of non-Hodgkin lymphoma.

Truxima has been approved as a biosimilar, not as an interchangeable product. A biosimilar is a biological product that is approved based on data showing that it is highly similar to a biological product already approved by the FDA and has no clinically meaningful differences in terms of safety, purity, and potency from the reference product, in addition to meeting other criteria specified by law. With the Truxima approval, the FDA has approved 15 biosimilars.

FDA Grants Accelerated Approval to Keytruda for Hepatocellular Carcinoma
The U.S. Food and Drug Administration has granted accelerated approval to Merck’s Keytruda (pembrolizumab) for people with hepatocellular carcinoma who have been previously treated with sorafenib. As a condition of accelerated approval, further studies are required. 

FDA Approves First-Line Treatment for Peripheral T-Cell Lymphoma Under New Review Pilot
The FDA has expanded the approved use of Adcetris (brentuximab vedotin) injection in combination with chemotherapy for adults with certain types of peripheral T-cell lymphoma (PTCL). This is the first FDA approval for treatment of newly diagnosed PTCL, and the agency used a new review program to complete the approval more quickly.

“The Real-Time Oncology Review (RTOR) program allows the FDA to access key data prior to the official submission of the application allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” says Richard Pazdur, md, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products. “When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review. RTOR allowed the FDA to approve this indication within two weeks of the completed application’s submission.”

Adcetris, which is manufactured by Seattle Genetics, is a monoclonal antibody that binds to a protein (called CD30) found on some cancer cells. Adcetris is now approved to treat previously untreated systemic anaplastic large cell lymphoma and other CD30-expressing PTCLs in combination with chemotherapy. 

Lorbrena Approved to Treat ALK-Positive Metastatic Non-Small Cell Lung Cancer 
Pfizer’s Lorbrena (lorlatinib) has been granted accelerated approval to treat people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 

Keytruda in Combination with Chemotherapy Gains Approval as First-Line Treatment of Metastatic Squamous Non-Small Cell Lung Cancer 
The FDA has approved Merck’s Keytruda (pembrolizumab) in combination with carboplatin and either paclitaxel or nab-paclitaxel as first-line treatment of metastatic squamous non-small cell lung cancer. The FDA granted this application priority review.

FDA Approves Herzuma as a Biosimilar to Herceptin
Celltrion’s Herzuma (trastuzumab-pkrb) has been approved by the FDA as a biosimilar to Genentech’s Herceptin (trastuzumab) for people with HER2-overexpressing breast cancer. Herzuma is a HER2/neu receptor antagonist indicated for the treatment of HER2-overexpressing breast cancer. Herzuma has been approved as a biosimilar, not as an interchangeable product.

Talzenna Approved to Treat Certain Locally Advanced or Metastatic Breast Cancers
The U.S. Food and Drug Administration has approved Pfizer’s Talzenna (talazoparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, for people with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2‑negative locally advanced or metastatic breast cancer. People must be selected for therapy based on an FDA-approved companion diagnostic for talazoparib. The FDA granted this application priority review.

The FDA also approved Myriad Genetic Laboratories’ BRACAnalysis CDx test to identify people with breast cancer with deleterious or suspected deleterious gBRCAm who are eligible for talazoparib. 

FDA Approves Expanded Use of Gardasil 9 to Include Individuals 27 Through 45 Years Old
The FDA has approved a supplemental application for Merck’s Gardasil 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) expanding the approved use of the vaccine to include women and men aged 27 through 45 years. Gardasil 9 prevents certain cancers and diseases caused by the nine HPV types covered by the vaccine.

Gardasil, a vaccine approved by the FDA in 2006 to prevent certain cancers and diseases caused by four HPV types (and the precursor to Gardasil 9), is no longer distributed in the U.S. In 2014, the FDA approved Gardasil 9, which covers the same four HPV types as Gardasil, as well as an additional five HPV types. Gardasil 9 was previously approved for use in males and females aged 9 through 26 years.

FDA Authorizes First Next Generation Sequencing-Based Test to Detect Very Low Levels of Remaining Cancer Cells in People with Acute Lymphoblastic Leukemia or Multiple Myeloma
ClonoSEQ assay, a next generation sequencing-based test for minimal residual disease in people with acute lymphoblastic leukemia or multiple myeloma, has been approved by the FDA. Minimal residual disease, or MRD, is a measure of the amount of cancer cells remaining in a person’s bone marrow. MRD is useful to evaluate in people who have responded to therapy when their tumor burden is below what can be detected with standard methods. The detection of MRD is associated with recurrence of the disease in those people. 

The ClonoSEQ assay, which is marketed by Adaptive Biotechnologies, is an in vitro diagnostic that uses multiplex polymerase chain reaction-based assays and next generation sequencing to identify and quantify certain gene sequences in DNA extracted from bone marrow from people with ALL or multiple myeloma. The ClonoSEQ assay measures the amount of MRD and is capable of detecting MRD at levels below 1 in 1 million cells. 

First Treatment for Advanced Form of the Second Most Common Skin Cancer Gains FDA Approval
Libtayo (cemiplimab-rwlc) injection for intravenous use has been granted FDA approval for the treatment of people with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation. This is the first FDA approval of a drug specifically for advanced cutaneous squamous cell carcinoma. Cutaneous squamous cell carcinoma is the second most common skin cancer in the U.S. 

Libtayo, which is marketed by Regeneron Pharmaceuticals, works by targeting the cellular pathway known as PD-1 (a protein found on the body’s immune cells and some cancer cells). By blocking this pathway, the drug may help the body’s immune system fight the cancer cells.

Vizimpro Approved to Treat Metastatic Non-Small Cell Lung Cancer
The FDA has approved Pfizer’s Vizimpro (dacomitinib), a kinase inhibitor, for the first-line treatment of people with metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test. Earlier this year, the FDA granted Priority Review for Vizimpro for the first-line treatment of people with locally advanced or metastatic non-small cell lung cancer with EGFR-activating mutations. The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. 

FDA Approves Copiktra for Adults with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma 
The FDA has granted regular approval to Verastem’s Copiktra (duvelisib) for adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after at least two prior therapies. In addition, Copiktra received accelerated approval for adults with relapsed or refractory follicular lymphoma after at least two prior systemic therapies.

New Kind of Treatment for Hairy Cell Leukemia Receives FDA Approval
Lumoxiti (moxetumomab pasudotox-tdfk) injection for intravenous use has been granted FDA approval for the treatment of adults with relapsed or refractory hairy cell leukemia who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Lumoxiti, which is marketed by AstraZeneca, is a CD22-directed cytotoxin and is the first of this type of treatment for people with hairy cell leukemia. The FDA granted this application Fast Track and Priority Review designations. Lumoxiti also received Orphan Drug designation, which provides incentives to aid and encourage the development of drugs for rare diseases.

FDA Approves Updates to Kyprolis Indication for People with Relapsed or Refractory Multiple Myeloma
The FDA has approved the supplemental New Drug Application to expand the prescribing information for Amgen’s Kyprolis (carfilzomib) to include a once-weekly dosing option in combination with dexamethasone (once-weekly Kd70) for people with relapsed or refractory multiple myeloma. The FDA reviewed the application under its Oncology Center of Excellence Real-Time Oncology Review and Assessment Aid pilot programs, which aim to explore a more efficient review process to ensure that safe and effective treatments are available to people as early as possible. The FDA approved the application in just over one month after its final submission.

Yervoy Granted Accelerated Approval to Treat Certain Metastatic Colorectal Cancers
The Food and Drug Administration has granted accelerated approval to Bristol-Myers Squibb’s Yervoy (ipilimumab) for use in combination with nivolumab for the treatment of people 12 years of age and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. 

This new use has also been added to the Opdivo (nivolumab) labeling. Further studies are required to confirm clinical benefit of ipilimumab and nivolumab for this indication. 

Prescribing Information for Keytruda and Tecentriq Updated 
The prescribing information for Keytruda (pembrolizumab) and Tecentriq (atezolizumab) has been updated to require the use of an FDA-approved companion diagnostic test to determine PD-L1 levels in tumor tissue from people with locally advanced or metastatic urothelial cancer who are cisplatin-ineligible. The FDA also approved two different companion diagnostic tests, one for use with Keytruda and one for use with Tecentriq.

Dako North America’s Dako PD-L1 IHC 22C3 PharmDx Assay has been approved by the FDA as a companion diagnostic to select people with locally advanced or metastatic urothelial carcinoma who are cisplatin-ineligible for treatment with Keytruda. The 22C3 assay determines PD-L1 expression by using a combined positive score assessing PD-L1 staining in tumor and immune cells. 

Ventana Medical Systems’ Ventana PD-L1 (SP142) Assay has been approved by the FDA as a companion diagnostic test to select people with locally advanced or metastatic urothelial carcinoma who are cisplatin-ineligible for treatment with Tecentriq. The SP142 assay determines PD L1 expression in immune cells. 

The FDA updated the prescribing information for both drugs to require use of an FDA-approved test for selection of people being treated in the first-line setting who are cisplatin-ineligible. The second-line indications in urothelial carcinoma for both drugs remain unchanged. 

FDA Approves First Targeted Treatment for People with Relapsed or Refractory Acute Myeloid Leukemia Who Have a Certain Genetic Mutation
The FDA has approved Agios Pharmaceuticals’ Tibsovo (ivosidenib) tablets for the treatment of adults with relapsed or refractory acute myeloid leukemia who have a specific genetic mutation. This is the first drug in its class (IDH1 inhibitors), and it is approved for use with an FDA-approved companion diagnostic used to detect specific mutations in the IDH1 gene in people with AML.

Tibsovo is an isocitrate dehydrogenase-1 inhibitor that works by decreasing abnormal production of the oncometabolite 2-hydroxyglutarate (2-HG), leading to differentiation of malignant cells. If the IDH1 mutation is detected in blood or bone marrow samples using an FDA-approved test, the person may be eligible for treatment with Tibsovo. The FDA also approved Abbott Laboratories’ RealTime IDH1 Assay, a companion diagnostic that can be used to detect this mutation.

Magnetic Device System for Guiding Sentinel Lymph Node Biopsies in Certain People with Breast Cancer Receives FDA Approval
The FDA has granted approval to a magnetic device system for guiding lymph node biopsies in people with breast cancer undergoing mastectomy. Endomagnetics’ Magtrace and Sentimag Magnetic Localization System uses magnetic detection during sentinel lymph node biopsy procedures to identify specific lymph nodes, known as sentinel lymph nodes, for surgical removal.

“This magnetic system [...] will offer patients undergoing mastectomy an option for their sentinel lymph biopsy procedure that does not require the injection of radioactive materials,” says Binita Ashar, MD, director of the Division of Surgical Devices in the FDA’s Center for Devices and Radiological Health. 

First Treatment for Rare Adrenal Tumors Receives FDA Approval
Progenics Pharmaceuticals’ Azedra (iobenguane I 131) injection for intravenous use has been approved for the treatment of adults and adolescents age 12 and older with rare tumors of the adrenal gland (pheochromocytoma or paraganglioma) that cannot be surgically removed, have spread beyond the original tumor site, and require systemic anticancer therapy. This is the first FDA-approved drug for this use.

As it is a radioactive therapeutic agent, Azedra includes a warning about radiation exposure to patients and family members which should be minimized while the patient is receiving Azedra. The risk of radiation exposure is greater in pediatric cancer survivors. 

FDA Approves Treatment for Two Rare Types of Non-Hodgkin Lymphoma
The FDA has approved Kyowa Kirin’s Poteligeo (mogamulizumab-kpkc) injection for intravenous use for the treatment of adults with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior systemic therapy. Poteligeo is a monoclonal antibody that binds to a protein found on some cancer cells. 

Opdivo Granted Accelerated Approval for Third-Line Treatment of Metastatic Small Cell Lung Cancer
The FDA has granted accelerated approval to Bristol-Myers Squibb’s Opdivo (nivolumab) for people with metastatic small cell lung cancer with progression after platinum-based chemotherapy and at least one other line of therapy. As a condition of accelerated approval, further studies are required to confirm benefit of Opdivo for this indication. This application was also granted Priority Review. 

FDA Approves Lenvima for Unresectable Hepatocellular Carcinoma
The FDA has approved Eisai Inc. and Merck’s kinase inhibitor Lenvima (lenvatinib) capsules for first-line treatment of people with unresectable hepatocellular carcinoma. Lenvima was first approved in 2015 for people with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer. In 2016, Lenvima was approved, in combination with everolimus, for people with advanced renal cell carcinoma following one prior anti-angiogenic therapy.

Xtandi Approved as Treatment for Castration-Resistant Prostate Cancer
Astellas Pharma’s Xtandi (enzalutamide) has been approved by the U.S. Food and Drug Administration to treat men with castration-resistant prostate cancer. This approval broadens the indicated patient population to include men with both non-metastatic castration-resistant prostate cancer and metastatic castration-resistant prostate cancer. 

FDA Approves First Cancer Drug – Kisqali for Breast Cancer – Through New Oncology Review Pilot That Enables Greater Development Efficiency
The FDA has approved Novartis’s Kisqali (ribociclib) in combination with an aromatase inhibitor for the treatment of pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, as initial endocrine-based therapy. The FDA also approved Kisqali in combination with fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer as initial endocrine based therapy or following disease progression on endocrine therapy.

This is the first approval that the FDA has granted as a part of two new pilot programs that collectively aim to make the development and review of cancer drugs more efficient. The first new program, called Real-Time Oncology Review, allows for the FDA to review much of the data earlier, after the clinical trial results become available and the database is locked, before the information is formally submitted to the FDA. The second program is a new templated Assessment Aid that the applicant uses to organize its submission into a structured format to facilitate FDA’s review. 

“With this approval, we’ve demonstrated some of the benefits of the new programs that we’re piloting for our review of cancer drugs, to improve regulatory efficiency while enhancing the process for evaluating the data submitted to us. This shows that, with smart policy approaches, we can gain efficiency while also improving the rigor of our process. These new programs were designed to reduce some of the administrative issues that can add to the time and cost of the review process, including the staffing burdens on the FDA. For example, by analyzing data earlier in the process, before formal submission to the FDA, and evaluating submissions in a structured template, we can make it easier to identify earlier when applications are missing key analysis or information that can delay reviews,” says FDA Commissioner Scott Gottlieb, MD. “With [this] approval, the FDA used these new approaches to allow the review team to start analyzing data before the actual submission of the application and help guide the sponsor’s analysis of the top-line data to tease out the most relevant information. This enabled our approval less than one month after the […] submission date and several months ahead of the goal date.

“These new processes are good for patients, good for healthcare providers, good for product developers, and good for the FDA, by allowing our staff to have more time to engage with product developers and focus on the key aspects of drug reviews. We can improve efficiency and solidify our gold standard for review.”

Currently the two pilot programs are being used for supplemental applications for already-approved cancer drugs and could later be expanded to original drugs and biologics.

FDA Grants Regular Approval for Keytruda in Combination with Chemotherapy for First-Line Treatment of Metastatic Nonsquamous Non-Small Cell Lung Cancer 
Merck’s Keytruda (pembrolizumab) in combination with pemetrexed and platinum has received FDA approval as first-line treatment of people with metastatic, non-squamous non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations.

Pembrolizumab was previously granted accelerated approval for this indication in May 2017. The current approval represents fulfillment of a postmarketing commitment demonstrating the clinical benefit of this product. This is the second FDA approval using the Real Time Oncology Review pilot program that enabled the FDA review team to begin analyzing data before the application submission.

Avastin, in Combination with Chemotherapy, Approved as Ovarian Cancer Treatment
The U.S. Food and Drug Administration has approved Avastin (bevacizumab) in combination with carboplatin and paclitaxel, followed by single-agent bevacizumab, for women with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer after initial surgical resection. The FDA granted Avastin, which is marketed by Genentech, orphan product designation for this indication. 

“This approval represents an important milestone as the first medicine, other than chemotherapy, for women with advanced ovarian cancer after their initial surgery,” says Melissa Aucoin, chief executive officer of the National Ovarian Cancer Coalition. 

Avastin is now approved for ten distinct uses across six different types of cancer in the United States. This indication represents Avastin’s fourth gynecologic oncology indication in four years.

FDA Approves Braftovi and Mektovi in Combination to Treat Unresectable or Metastatic Melanoma with BRAF Mutations
The FDA has granted approval to Array BioPharma’s Braftovi (encorafenib) capsules in combination with its Mektovi (binimetinib) tablets for the treatment of people with unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation, as detected by an FDA-approved test. Braftovi is not indicated for the treatment of people with wild-type BRAF melanoma. The FDA also granted approval to bioMérieux’s THxID BRAF Kit as a companion diagnostic for these therapies.

Keytruda Gains Approval for Treatment of Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma 
Keytruda (pembrolizumab) has been granted accelerated approval for the treatment of adults and children with refractory primary mediastinal large B-cell lymphoma (PMBCL), or those who have relapsed after two or more prior lines of therapy. 

The FDA granted this application priority review. Keytruda, which is marketed by Merck, also received orphan product designation and breakthrough therapy designation for the PMBCL indication. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon Keytruda’s performance in confirmatory trials. 

FDA Approves Keytruda for Advanced Cervical Cancer 
The FDA has also approved Merck’s Keytruda (pembrolizumab) for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 as determined by an FDA-approved test. The FDA also approved Dako North America’s PD-L1 IHC 22C3 pharmDx as a companion diagnostic.

This indication for Keytruda is approved under the FDA’s accelerated approval program based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The FDA also granted this application priority review. 

Venclexta Approved to Treat People with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
AbbVie Inc. and Genentech’s Venclexta (venetoclax) has been granted regular approval to treat people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy. The FDA granted Venclexta in combination with rituximab breakthrough therapy designation and granted this application priority review. 

FDA Approves First Biosimilar to Neulasta to Help Reduce the Risk of Infection During Cancer Treatment
The FDA has approved Mylan’s Fulphila (pegfilgrastim-jmdb) as the first biosimilar to Neulasta (pegfilgrastim) to decrease the chance of infection as suggested by febrile neutropenia (which is fever, often with other signs of infection, associated with an abnormally low number of infection-fighting white blood cells), in people with non-myeloid (or non-bone marrow) cancer who are receiving myelosuppressive chemotherapy that has a clinically significant incidence of febrile neutropenia.

A biosimilar is a biological product that is approved based on data showing that it is highly similar to a biological product already approved by the FDA and has no clinically meaningful differences in terms of safety, purity, and potency (in other words, safety and effectiveness) from the reference product, in addition to meeting other criteria specified by law. 

The FDA’s approval of Fulphila is based on review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Fulphila is biosimilar to Neulasta. Fulphila has been approved as a biosimilar, not as an interchangeable product.

Retacrit Approved as a Biosimilar to Epogen/Procrit
Hospira’s Retacrit (epoetin alfa-epbx) has been approved by the FDA as a biosimilar to Amgen’s Epogen/Procrit (epoetin alfa) for the treatment of anemia due to chronic kidney disease in people on dialysis and not on dialysis, the use of zidovudine in people with HIV infection, and the effects of concomitant myelosuppressive chemotherapy. It is also approved for the reduction of allogeneic red blood cell transfusions in people undergoing elective, noncardiac, nonvascular surgery.

The approval was based on comparisons of extensive structural and functional product characterization, animal data, human pharmacokinetic and pharmacodynamic data, and clinical immunogenicity between Retacrit and Epogen/Procrit demonstrating that Retacrit is highly similar to Epogen/Procrit and that there are no clinically meaningful differences between the products. Retacrit has not been shown to be interchangeable with Epogen/Procrit. Like Epogen/Procrit, the labeling for Retacrit contains a Boxed Warning to alert healthcare professionals and patients about an increased risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.