Understanding Cancer FDA Updates

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

Keytruda Plus Axitinib Approved to Treat Advanced Renal Cell Carcinoma
The U.S. Food and Drug Administration has approved Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with Inlyta (axitinib), a tyrosine kinase inhibitor, for the first-line treatment of people with advanced renal cell carcinoma. The approval is based on findings from a phase III trial which demonstrated significant improvements in overall survival, progression-free survival, and objective response rate for Keytruda in combination with axitinib compared to sunitinib. The FDA granted this application Priority Review and Breakthrough Therapy designation. 

FDA Approves First Targeted Therapy for Metastatic Bladder Cancer
The FDA has granted accelerated approval to Balversa (erdafitinib), a treatment for adults with locally advanced or metastatic bladder cancer that has a type of susceptible genetic alteration known as FGFR3 or FGFR2, and that has progressed during or following prior platinum-containing chemotherapy. People should be selected for therapy with Balversa using an FDA-approved companion diagnostic device.

“We’re in an era of more personalized or precision medicine, and the ability to target cancer treatment to a patient’s specific genetic mutation or biomarker is becoming the standard, with advances being made in new disease types. [This] approval represents the first personalized treatment targeting susceptible FGFR genetic alterations for patients with metastatic bladder cancer,” 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. 

Balversa received an Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need using clinical trial data that is thought to predict a clinical benefit. Further clinical trials are required to confirm Balversa’s clinical benefit. Balversa was also granted Breakthrough Therapy designation. The FDA granted the approval of Balversa to Janssen Pharmaceutical.

The FDA also approved the therascreen FGFR RGQ RT-PCR Kit, developed by Qiagen Manchester, Ltd., for use as a companion diagnostic with Balversa for this therapeutic indication.

FDA Expands Keytruda Indication for First-Line Treatment of Non-Small Cell Lung Cancer 
The FDA has approved an expanded label for Merck’s Keytruda (pembrolizumab) as monotherapy for the first-line treatment of people with stage III non-small cell lung cancer who are not candidates for surgical resection or definitive chemoradiation, or metastatic non-small cell lung cancer, and whose tumors express PD-L1 (tumor proportion score [TPS] ≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

Keytruda, which is marketed by Merck, was previously approved as a single agent for the first-line treatment of people with metastatic non-small cell lung cancer whose tumors express PD-L1 TPS ≥50%.

Ibrance Approved to Treat Men with HR+, HER2- Metastatic Breast Cancer
The FDA has approved a supplemental New Drug Application to expand the indications for Pfizer’s Ibrance (palbociclib) in combination with an aromatase inhibitor or fulvestrant to include men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. The approval is based on data from electronic health records and postmarketing reports of the real-world use of Ibrance in men with breast cancer. 

“With this approval, we are now able to offer IBRANCE to the underserved male breast cancer community and provide more patients with HR+, HER2- metastatic breast cancer the opportunity to access an innovative medicine,” says Chris Boshoff, MD, PhD, chief development officer for oncology at Pfizer Global Product Development.

FDA Approves Tecentriq for PD-L1 Positive Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer
The FDA has granted accelerated approval to Genentech’s Tecentriq (atezolizumab) in combination with paclitaxel protein-bound for adults with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells of any intensity covering ≥ 1% of the tumor area), as determined by an FDA-approved test. The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic device for selecting people with triple-negative breast cancer as candidates for Tecentriq. 

This indication for Tecentriq is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Tecentriq in Combination with Chemotherapy Receives FDA Approval for the Initial Treatment of Adults with Extensive-Stage Small Cell Lung Cancer
Tecentriq (atezolizumab), in combination with carboplatin and etoposide, has been granted FDA approval for the initial treatment of adults with extensive-stage small cell lung cancer. This approval is based on results from a phase III study which showed that Tecentriq in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone. 

“Tecentriq is the first cancer immunotherapy approved for the initial treatment of extensive-stage small cell lung cancer, which is especially difficult to treat,” says Sandra Horning, md, chief medical officer and head of Global Product Development at Genentech. “Until now, there have been limited treatment advances for this disease, and we are excited to bring a potential new standard of care to patients that has been shown to improve survival compared to chemotherapy.”

Tecentriq, which is marketed by Genentech, is also approved in combination with bevacizumab, paclitaxel, and carboplatin for the initial treatment of adults with metastatic non-squamous non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations. Additionally, Tecentriq is approved by the FDA to treat adults with metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy. 

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.