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Atezolizumab Fda Approval Bladder Cancer

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Use In Specific Populations

FDA Approval of Atezolizumab for Advanced Bladder Cancer

Atezolizumab can cause fetal harm. Women of reproductive age should use effective contraception during atezolizumab therapy and for 5 months after the last dose. Female fertility may be compromised with atezolizumab therapy.8

Women should not breastfeed while using atezolizumab and for at least 5 months after the last dose.8

Atezolizumab has not been studied in children. No differences in its safety and effectiveness were observed between patients aged 65 years with urothelial carcinoma and younger patients, or between patients with NSCLC aged 75 years and younger patients.8

No dose adjustment is needed in patients with renal impairment or with mild hepatic impairment. Atezolizumab has not been studied in moderate or severe hepatic impairment.8

The Approval Provides The First New Treatment Option In More Than 30 Years For Patients With The Most Common Type Of Bladder Cancer

A first-of-its kind immunotherapeutic, atezolizumab , was recently approved by the U.S. Food and Drug Administration for treating certain patients with advanced bladder cancer.

Atezolizumab is intended for patients with locally advanced or metastatic urothelial carcinoma the most common form of bladder cancer ? whose disease has progressed during or following treatment with platinum-based chemotherapy or whose disease progressed within 12 months of platinum-based chemotherapy given before or after surgery.

Bladder cancer is the fifth most commonly diagnosed cancer in the United States. An estimated 76,960 U.S. adults will be diagnosed with bladder cancer and 16,390 people will die from the disease in 2016. Urothelial carcinoma accounts for 90 percent of all cases, according to Roche, the company that manufactures atezolizumab.

Prior to the approval of atezolizumab, there were no FDA-approved treatment for patients with metastatic urothelial carcinoma that had progressed despite platinum-based chemotherapy, and the outlook for these patients was poor, with median survival of around five to seven months.

Two immunotherapeutics that release the PD-1 brake on T cells by targeting PD-1, nivolumab and pembrolizumab , have already been approved by the FDA for treating certain patients with a variety of cancer types.

The FDA approval was rendered on May 17, 2016.

Introduction To Bladder Cancer

The treatment landscape for urothelial carcinoma has undergone a renaissance. Since 2017, eight new medications have received approval from the US Food and Drug Administration for the treatment of this disease. These new therapies include five immune checkpoint inhibitors , though one subsequently withdrew its UC indication, two antibody-drug conjugates and one tyrosine kinase inhibitor .

ICIs have improved outcomes for patients with UC with multiple agents showing efficacy in different treatment settings. Currently, there is level 1 evidence to support the use of ICIs for patients previously treated with platinum-based chemotherapy, either as switch-maintenance therapy for those with non-progressive disease or some response to platinum chemotherapy or for platinum-refractory disease as a second line or salvage therapy. Additional treatment indications include for treatment-naive patients with locally advanced, unresectable or metastatic UC who are cisplatin-ineligible with high PD-L1 expression, or for patients who are platinum-ineligible , for BCG-refractory non-muscle invasive bladder cancer with carcinoma in situ and as an adjuvant therapy after extirpative surgery. Clinical trials are ongoing further exploring additional perioperative approaches and combination therapies.

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Small Cell Lung Cancer

  • FDA: Recommended dosage of Tecentriq is 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks. Administer Tecentriq prior to chemotherapy when given on the same day until disease progression or unacceptable toxicity.
  • NCCN: carboplatin AUC 5 day 1 and etoposide 100 mg/m2 days 1, 2, 3 and atezolizumab 1200 mg day 1 every 21 days for 4 cycles followed by maintenance atezolizumab 1680 mg day 1, every 28 days. Four cycles of therapy are recommended, but some individuals may receive up to 6 cycles based on response and tolerability after 4 cycles. Not recommended for relapsed disease in persons on maintenance atezolizumab at time of relapse. For persons who relapse after greater than 6 months of atezolizumab maintenance therapy, NCCN recommends re-treatment with carboplatin plus etoposide alone.

Roche Withdraws Tecentriq For Bladder Cancer After Fda Accelerated Approval Review

Checkpoint Inhibitors Changing Landscape for Advanced Solid Tumors

This article has been updated to note that atezolizumab is approved in the US for first-line metastatic bladder cancer and that the confirmatory study, IMvigor211, did not meet its primary endpoint rather than the IMvigor 210 trial as previously reported.

NEW YORK Roche said on Monday it will withdraw the indication of atezolizumab in previously treated bladder cancer after a review of accelerated approvals by the US Food and Drug Administration.

Roche is voluntarily withdrawing the bladder cancer indication because the confirmatory study for the accelerated approval, IMvigor211, did not meet its primary endpoint in patients who were previously treated with platinum chemotherapy. As the treatment landscape for bladder cancer has advanced, atezolizumab does not fill an unmet medical need as required by the accelerated approval program, and Roche is “withdrawing this indication in recognition of the principles of the Accelerated Approval Program,” the company said.

Atezolizumab was granted accelerated approval for bladder cancer by the FDA in 2016 based on results from the IMvigor210 trial. Full approval was contingent upon positive results from the IMvigor211 study, however, that trial showed the drug did not improve overall survival in the PD-L1-high patient population.

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Odac Says Yes To Continued Approval Of Atezolizumab For Cisplatin

The FDAs Oncologic Drug Advisory Committee voted 10 to 1 to continue the accelerated approval of atezolizumab for the frontline treatment of patients with urothelial cancer who are ineligible for cisplatin.

The FDAs Oncologic Drug Advisory Committee voted 10 to 1 to continue the accelerated approval of atezolizumab for the frontline treatment of patients with urothelial cancer who are ineligible for cisplatin.1

In my personal opinion, the positive vote by ODAC to maintain the accelerated approval for both checkpoint inhibitors likely reflects the lack of standard of care for unfit patients with chemotherapy-ineligible metastatic bladder cancer. Although it remains unclear if we will ever see a confirmatory trial demonstrating OS benefit to either agent in that particular setting, having the opportunity to receive one of these agents at present time is critically important for those patients in need of treatments outside chemotherapy, Jorge A. Garcia, MD, FACP, a non-voting ODAC member and chief, Division of Solid Tumor Oncology interim chief, Divisions of Hematology/Hematologic Malignancies George and Edith Richman Distinguished Scientist Chair professor of medicine and urology and director, GU Oncology Program, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center told Targeted Oncology in an interview.

Reference:

Criteria For Initial Approval

Aetna considers atezolizumab medically necessary for the following indications:

  • Urothelial Carcinoma – Bladder Cancer

    For treatment as a single agent for bladder cancer when the requested medication is used as first line therapy in cisplatin ineligible members whose tumors express PD-L1 or in members who are not eligible for any platinum containing chemotherapy regardless of PD-L1 expression for any of the following:

  • Stage II or Stage IIIa disease if tumor is present following reassessment of tumor status 2-3 months after primary treatment with concurrent chemoradiotherapy or
  • Stage IIIb disease as downstaging systemic therapy or following partial response or progression after primary treatment with concurrent chemoradiotherapy or
  • Locally advanced or metastatic disease or
  • Metastatic or local recurrence post-cystectomy or
  • Muscle invasive local recurrence or presistent disease in a preserved bladder
  • Urothelial Carcinoma – Primary Carcinoma of the Urethra

    For treatment as a single agent for primary carcinoma of the urethra when the requested medication is used as first line therapy for recurrent, locally advanced or metastatic disease in cisplatin ineligible members whose tumors express PD-L1 or in members who are not eligible for any platinum containing chemotherapy regardless of PD-L1 expression

  • Non-small Cell Lung Cancer

    For treatment of NSCLC when the tumor is negative for EGFR, ALK, and RET gene mutations and any of the following criteria are met:

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    Atezolizumab Fda Indication For Pretreated Bladder Cancer Voluntarily Withdrawn

    The withdrawal comes after the confirmatory phase 3 IMvigor211 study missed its primary end point.

    Roche has voluntarily withdrawn the FDA indication for the PD-L1 inhibitor atezolizumab for use in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based chemotherapy.1

    Atezolizumab received an accelerated approval from the FDA for this indication in May 2016 based on cohort data from the phase 2 IMvigor210 study.2 However, an FDA accelerated approval is contingent upon the results of a confirmatory trial, and in May 2017, Roche reported that the phase 3 IMvigor211 study exploring atezolizumab in the second-line setting for patients with locally advanced or missed its primary end point of improving overall survival .3

    The Accelerated Approval Program allows people with difficult-to-treat cancers to receive certain new therapies earlier, Levi Garraway, MD, PhD, Roches chief medical officer and head of global product development, stated in a press release. While the withdrawal of Tecentriq for prior-platinum treated bladder cancer is disappointing, Tecentriq continues to demonstrate benefits across multiple cancer types and therefore remains a meaningful treatment option for many patients.

    References

    Related Content:

    Atezolizumabs Indication In Previously Treated Metastatic Bladder Cancer Is Withdrawn

    Dr. Steinberg on the FDA Approval of Atezolizumab in Bladder Cancer

    3/31/2021 3:32:05 PM

    Genentech, a member of the Roche Group, announced on March 8 that the company is voluntarily withdrawing the U.S. indication for atezolizumab in patients with prior platinum-treated metastatic urothelial carcinoma. This decision was made in consultation with the U.S. Food and Drug Administration as part of an industry-wide review of accelerated approvals with confirmatory trials that have not met their primary endpoints and have yet to gain regular approvals.

    Atezolizumab is a monoclonal antibody designed to bind with the protein PD-L1, expressed on tumor cells and tumor-infiltrating immune cells, thereby blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the reactivation of T cells.

    The FDAs Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition, with specific postmarketing requirements to confirm the clinical benefit and convert to regular approval.

    Genentech will work with the FDA over the coming weeks to complete the withdrawal process. This decision does not affect other approved indications for atezolizumab.

    Genentech is notifying health-care professionals about this withdrawal. Patients being treated with atezolizumab for prior platinum-treated metastatic urothelial carcinoma should discuss their care with their health-care provider.

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    Tecentriq Approved For First

    On April 17, 2017, the US Food and Drug Administration granted accelerated approval to atezolizumab , a monoclonal antibody intravenous inhibitor of programmed-cell death ligand-1 , as detected by the FDA-approved test, as a front-line treatment for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy.5

    It is encouraging to see continued progress in the treatment of advanced bladder cancer, which until last year had not seen any major advancements in more than 30 years,5 said Andrea Maddox Smith, Chief Executive Officer, Bladder Cancer Advocacy Network. We are excited that TECENTRIQ is now a treatment option for people with advanced bladder cancer who are unable to receive a cisplatin-based chemotherapy as an initial treatment.5

    Atezolizumab initially received accelerated approval in May 2016 for the treatment of locally advanced or metastatic urothelial carcinoma that progressed during or after platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.6,7 This was the first FDA approval of a PD-L1 inhibitor for any malignancy.6 The 2 approvals for urothelial carcinoma are contingent on results from ongoing phase 3 clinical trials.8

    Us Food And Drug Administration

    • Locally advanced or metastatic urothelial carcinoma

      Indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who:

    • Are not eligible for cisplatin-containing chemotherapy, and whose tumors express PD-L1 , as determined by an FDA-approved test, or
    • Are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status
  • Metastatic non-small cell lung cancer

  • Indicated as a single-agent for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage II to IIIA non-small cell lung cancer whose tumors have PD-L1 expression on 1% of tumor cells, as determined by an FDA-approved test
  • Indicated as a single agent for the first line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression , as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations
  • Indicated in combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment, of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations
  • Indicated in combination with paclitaxel protein-bound and carboplatin for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations
  • Small cell lung cancer

    Indicated in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer .

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    Fda Approves Tecentriq For Small Cell Lung Cancer

    The US Food and Drug Administration has approved the immunotherapy drug Tecentriq for the treatment of small cell lung cancer . Its the second immunotherapy drug approved for people with advanced SCLC, but the first approved for use as part of the initial treatment. Its to be used along with chemotherapy for SCLC that has not already been treated with other drugs.

    About 10% to 15% of lung cancers are small cell lung cancer. This type of cancer is often advanced when its first found, and patients with this cancer typically dont have many treatment options. Whats more, very few new drugs have been approved to treat SCLC over the past 20 years.

    Tecentriq is a type of drug called a checkpoint inhibitor. It works by blocking PD-L1, a protein on some cancer cells that prevents the immune system from attacking them. Its already approved to treat people with non-small cell lung cancer, bladder cancer, and triple-negative breast cancer.

    The FDA based this latest approval on a clinical trial of 403 people that focused mainly on overall survival how long patients lived after starting treatment. Half the patients received Tecentriq along with the standard chemotherapy drugs carboplatin and etoposide, and the other half received a placebo, carboplatin, and etoposide. After an average follow-up period of about 14 months, average survival was 12.3 months in the Tecentriq group compared with 10.3 months in the placebo group.

    Tecentriq is marketed by F. Hoffmann-La Roche/Genentech.

    Clinical Evidence Of Nivolumab

    Tecentriq Genentech Atezolizumab Injection, M/s G M Global

    Non-Muscle Invasive Bladder Cancer

    The majority of patients with UC present with hematuria and are found to have non-muscle invasive disease, which is generally associated with better outcomes given its earlier stage. However, for high-risk non-muscle invasive bladder cancer , patients have a greater risk of progression to muscle-invasive bladder cancer or metastatic disease. Therefore, these high-risk patients are treated with intravesical Bacillus Calmette-Guérin , an attenuated strain of Mycobacterium bovis, that has been the primary immunotherapy treatment option for several decades. For patients with BCG unresponsive disease, guidelines suggest pursuing radical cystectomy, which can result in increased risk of mortality from major surgery or increased morbidity and a lower quality of life.6 Bladder sparing options in this clinical scenario have historically been limited and have relied upon the use of intravesical chemotherapy, including mitomycin, gemcitabine, valrubicin and more recently sequential gemcitabine and docetaxel. However, investigations into ICIs have also begun demonstrating activity in the NMIBC clinical setting.

    Table 1 Overview of Nivolumab Clinical Trials in Urothelial Carcinoma

    Muscle Invasive Bladder Cancer

    Metastatic Urothelial Carcinoma

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    First And Only Cancer Immunotherapy Approved In Advanced Bladder Cancer As Initial Treatment For Those Unable To Receive Cisplatin Chemotherapy

    South San Francisco, CA — April 17, 2017 —

    Genentech, a member of the Roche Group , today announced that the U.S. Food and Drug Administration granted accelerated approval to TECENTRIQ® for the treatment of people with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy. TECENTRIQ was previously approved for people with locally advanced or mUC who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery or after surgery . It is not known if TECENTRIQ is safe and effective in children. Bladder cancer is the most common type of urothelial carcinoma, and up to half of all people with the advanced form of the disease are unable to receive cisplatin chemotherapy as an initial treatment and therefore have a high unmet medical need. Urothelial carcinoma also includes cancers of the urethra, ureters and renal pelvis.

    It is encouraging to see continued progress in the treatment of advanced bladder cancer, which until last year had not seen any major advancements in more than 30 years, said Andrea Maddox Smith, chief executive officer, Bladder Cancer Advocacy Network. We are excited that TECENTRIQ is now a treatment option for people with advanced bladder cancer who are unable to receive a cisplatin-based chemotherapy as an initial treatment.

    About the IMvigor210 study

    About metastatic urothelial cancer

    About Genentech Access Solutions

    Disclosure Of Potential Conflicts Of Interest

    B.A. Inman reports receiving commercial research grants from Abbott Laboratories, Dendreon, Genentech, and GlaxoSmithKline and is a consultant/advisory board member for AstraZeneca, Combat Medical, Ferring, Genentech, and Taris Biomedical. M.R. Harrison reports receiving commercial research grants from Acerta and Genentech, speakers bureau honoraria from Genentech, and is a consultant/advisory board member for AstraZeneca and Genentech. No potential conflicts of interest were disclosed by the other authors.

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    Fda Grants Atezolizumab Accelerated Approval For Bladder Cancer

    The US Food and Drug Administration has granted the PD-L1-targeting monoclonal antibody atezolizumab accelerated approval for first-line treatment of advanced or metastatic urothelial carcinoma regardless of PD-L1 expression status in patients who are ineligible for frontline cisplatin chemotherapy, according to a press release.1

    Atezolizumab was previously FDA-approved for second-line treatment for advanced urothelial carcinomas refractory to platinum-containing chemotherapies or that had progressed within 12 months of neoadjuvant or adjuvant chemotherapy.

    The FDAs Accelerated Approval Program allows conditional approval of medications addressing unmet medical needs based on early evidence of clinical benefit continued approval depends on confirmatory data verifying benefit.

    This accelerated approval was based on data from the phase 2 IMvigor210 clinical trial, an open-label, multicenter, single-arm study, in which 119 patients had an objective response rate of 23.5% .

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    Serious adverse events potentially associated with atezolizumab include pneumonitis, hepatitis, colitis, endocrinopathies of the pituitary, thyroid, adrenal glands, and pancreas, neuropathy, meningitis, encephalitis, uveitis, and severe infections and infusion reactions. In the IMvigor210 trial, atezolizumab was discontinued because of treatment-related toxicities in 5 of 119 patients .

    Reference

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