Atezolizumab

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Atezolizumab
Atezolizumab PD-L1 5X8L.png
Antigen-binding fragment of atezolizumab (blue) in complex with PD-L1 (pink). PDB: 5X8L ​.
Monoclonal antibody
Type Whole antibody
Source Humanized
Target PD-L1
Clinical data
Trade names Tecentriq, Tecentriq SC
Other namesMPDL3280A, RG7446
AHFS/Drugs.com Monograph
MedlinePlus a616035
License data
Pregnancy
category
Routes of
administration 		Intravenous infusion, subcutaneous
Drug class Antineoplastic agent
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6446H9902N1706O1998S42
Molar mass 144612.59 g·mol−1

Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, [9] [11] but discontinued for use in triple-negative breast cancer (TNBC). [12] It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1). [13]

Contents

The most common side effects when used on its own include tiredness, reduced appetite, nausea, vomiting, cough, difficulty breathing, diarrhea, rash, fever, pain in the back, joints, muscles and bones, weakness, itching and urinary tract infection. [10] The most common side effects when used with other cancer medicines include peripheral neuropathy (nerve damage in the hands and feet), nausea, anemia (low red blood cell counts), neutropenia (low white blood cell counts), thrombocytopenia (low platelet counts), rash, tiredness, constipation, reduced appetite, diarrhea, and cough. [10]

Atezolizumab was the first PD-L1 inhibitor approved by the U.S. for bladder cancer. Food and Drug Administration (FDA). [14]

In the European Union, atezolizumab is the first PD-(L)1 cancer immunotherapy for subcutaneous injection. [15]

Medical uses

In the European Union, atezolizumab is indicated for the treatment of urothelial carcinoma, non-small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, urothelial carcinoma, and triple-negative breast cancer. [10] It is no longer indicated for triple-negative breast cancer. [12]

In the United States, atezolizumab is indicated for the treatment of non-small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. [9] [16] Its indication for urothelial carcinoma was withdrawn in November 2022. [17]

Adverse effects

The most common adverse effects in studies were fatigue, decreased appetite, nausea, and infections. Urinary tract infection was the most common severe adverse effect. [18]

Pharmacology

Mechanism of action

Non-small cell lung cancer (NSCLC) cells expressing programmed death-ligand 1 (PD-L1) could interact with programmed death receptor 1 (PD-1) expressed on the surface of T cells, and result in decreased tumor cell kill by the immune system. Atezolizumab is an anti PD-L1 monoclonal antibody. Nivolumab and pembrolizumab are anti PD-1 monoclonal antibodies. Ipilimumab is a monoclonal antibody that targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of T cells. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF) in the circulation and functions as an angiogenesis inhibitor. Source: First line Immunotherapy for Non-Small Cell Lung Cancer, Nasser NJ, Gorenberg M, Agbarya A. Pharmaceuticals (Basel). 2020 https://doi.org/10.3390/ph13110373 Immunotherapy + Durvalumab + Pembrolizumab + Ipilimumab + Atezolizumab mechanism of action.jpg
Non-small cell lung cancer (NSCLC) cells expressing programmed death-ligand 1 (PD-L1) could interact with programmed death receptor 1 (PD-1) expressed on the surface of T cells, and result in decreased tumor cell kill by the immune system. Atezolizumab is an anti PD-L1 monoclonal antibody. Nivolumab and pembrolizumab are anti PD-1 monoclonal antibodies. Ipilimumab is a monoclonal antibody that targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of T cells. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF) in the circulation and functions as an angiogenesis inhibitor. Source: First line Immunotherapy for Non-Small Cell Lung Cancer, Nasser NJ, Gorenberg M, Agbarya A. Pharmaceuticals (Basel). 2020 https://doi.org/10.3390/ph13110373

Atezolizumab blocks the interaction of PD-L1 with programmed cell death protein 1 (PD-1) and CD80 receptors (B7-1Rs). [20] PD-L1 can be highly expressed on certain tumors, which is thought to lead to reduced activation of immune cells (cytotoxic T-cells in particular) that might otherwise recognize and attack the cancer. [20] Inhibition of PD-L1 by atezolizumab can remove this inhibitor effect and thereby engender an anti-tumor response. It is one of several ways to block inhibitory signals related to T-cell activation, a more general strategy known as "immune checkpoint inhibition." [20]

For some cancers (notably bladder) the probability of benefit is related to PD-L1 expression, but most cancers with PD-L1 expression still do not respond, and many (about 15%) without PD-L1 expression do respond. [20]

History

In 2015, it was in clinical trials as an immunotherapy for several types of solid tumors. [13] It was under investigation by Genentech/Roche. [13]

In April 2016, Roche announced that atezolizumab had been granted fast track status for lung cancer by the U.S. Food and Drug Administration (FDA). [21]

In May 2016, the FDA granted accelerated approval to atezolizumab for locally advanced or metastatic urothelial carcinoma treatment after failure of cisplatin-based chemotherapy. [14] [22] The confirmatory trial (to convert the accelerated approval into a full approval) failed to achieve its primary endpoint of overall survival. [23] In 2018, FDA altered the use of atezolizumab as a first-line treatment for metastatic bladder cancer in people who can't receive cisplatin-based chemotherapy and have high levels of PD-L1. [24]

In May 2016, atezolizumab was approved by the FDA for the treatment of people with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within twelve months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. [25] [14] In May 2017, atezolizumab failed a phase III trial for second line bladder cancer. [26]

The safety and efficacy of atezolizumab were studied in people with urothelial carcinoma. [14] [25] [27] Tumors temporarily shrank in a minority of participants, with people being more likely to benefit if the tumor expressed PD-L1. [14] The trial was conducted in the United States, Canada, Spain, France, Great Britain, Germany, Italy and the Netherlands. [27]

In October 2016, atezolizumab was approved by the FDA for the treatment of people with metastatic non-small cell lung cancer (NSCLC) whose disease progressed during or following platinum-containing chemotherapy. [28] People with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab. [28]

This approval was based on two international, randomized, open-label clinical trials (OAK and POPLAR) that demonstrated consistent results in efficacy and safety in a total of 1137 participants with NSCLC. [28] Compared with docetaxel, treatment with atezolizumab in the intended participants population in the two trials resulted in a 4.2 and a 2.9 month improvement in overall survival (OS), respectively. [28]

Atezolizumab was approved for medical use in the European Union in September 2017. [10]

In May 2018, the use of atezolizumab in combination with bevacizumab (Avastin) and standard chemotherapy for some people with lung cancer was granted priority review. [29]

In August 2018, the FDA updated the prescribing information for atezolizumab 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. [30]

In September 2018, it was announced that atezolizumab prolongs survival in extensive stage SCLC treatment, according to study results presented at the 19th World Conference on Lung Cancer (WCLC) in Toronto, Canada.[ medical citation needed ]

In October 2018, a combined clinical trial of the drug with nab-paclitaxel on people with advanced TNBC concluded. [31]

Atezolizumab, in combination with bevacizumab, paclitaxel, and carboplatin, was approved in the United States in December 2018, for the first-line treatment of people with metastatic non-squamous, non-small cell lung cancer (NSq NSCLC) with no EGFR or ALK genomic tumor aberrations. [32] Approval was based on the IMpower150 trial (NCT02366143), an open-label, randomized (1:1:1), three-arm trial enrolling 1202 participants receiving first-line treatment for metastatic NSq NSCLC. [32]

In March 2019, it was approved in the United States, in combination with paclitaxel protein-bound, for adults with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering ≥ 1% of the tumor area), as determined by an FDA-approved test. [33] The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic device for selecting TNBC patients for atezolizumab. [34]

Approval was based on IMpassion130 (NCT02425891), a multicenter, international, double-blinded, placebo-controlled, randomized trial that included 902 participants with unresectable locally advanced or metastatic TNBC who had not received prior chemotherapy for metastatic disease. [34] Participants were randomized (1:1) to receive either atezolizumab (840 mg) or placebo intravenous infusions on days 1 and 15 of every 28-day cycle, plus paclitaxel protein-bound (100 mg/m2) administered via intravenous infusion on days 1, 8, and 15 of every 28-day cycle. [34]

Also in March 2019, it was approved in the United States, in combination with carboplatin and etoposide, for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC). [35]

Approval was based on IMpower133 (NCT02763579), a randomized (1:1), multicenter, double-blind, placebo-controlled trial in 403 participants with ES-SCLC who received no prior chemotherapy for extensive stage disease and had ECOG performance status 0 or 1. [35]

In December 2019, atezolizumab in combination with paclitaxel protein-bound and carboplatin was approved by the FDA for the first-line treatment of adults with metastatic non-squamous non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations. [36]

Efficacy was evaluated in IMpower130 (NCT02367781), a multicenter, randomized (2:1), open-label trial in participants with stage IV non-squamous NSCLC who had received no prior chemotherapy for metastatic disease, but could have received prior EGFR or ALK kinase inhibitor, if appropriate. [36] The trial randomized 724 participants (ITT) to either receive atezolizumab, paclitaxel protein-bound, and carboplatin, followed by single-agent atezolizumab, or to receive paclitaxel protein-bound and carboplatin, followed by maintenance pemetrexed at the investigator's discretion. [36]

In May 2020, the atezolizumab was approved by the FDA for the first-line treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (PD-L1 stained ≥ 50% of tumor cells [TC ≥ 50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 10% of the tumor area [IC ≥ 10%]), with no EGFR or ALK genomic tumor aberrations. [37]

Efficacy was evaluated in IMpower110 (NCT02409342), a multicenter, international, randomized, open-label trial in participants with stage IV NSCLC whose tumors express PD-L1 (TC ≥ 1% or IC ≥ 1%), who had received no prior chemotherapy for metastatic disease. [37] Participants were randomized (1:1) to receive atezolizumab 1200 mg every three weeks (until disease progression or unacceptable toxicity) or platinum-based chemotherapy. [37]

Also in May 2020, atezolizumab in combination with bevacizumab was approved by the FDA for people with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy. [38]

Efficacy was investigated in IMbrave150 (NCT03434379), a multicenter, international, open-label, randomized trial in participants with locally advanced unresectable or metastatic hepatocellular carcinoma who had not received prior systemic therapy. [38] A total of 501 participants were randomized (2:1) to receive either atezolizumab 1200 mg as an intravenous infusion (IV) followed by bevacizumab 15 mg/kg IV on the same day, every 3 weeks, or sorafenib orally twice daily. [38]

In July 2020, it was approved in the United States, in combination with cobimetinib and vemurafenib, for the treatment of people with BRAF V600 mutation-positive unresectable or metastatic melanoma. [39]

Efficacy in combination with cobimetinib and vemurafenib was evaluated in a double-blind, randomized (1:1), placebo-controlled, multicenter trial (IMspire150, NCT02908672) in 514 participants. [39] After a 28-day cycle of cobimetinib and vemurafenib, participants received atezolizumab 840 mg intravenous infusion every 2 weeks in combination with cobimetinib 60 mg orally once daily and vemurafenib 720 mg orally twice daily, or placebo in combination with cobimetinib 60 mg orally once daily (21 days on/7 days off) and vemurafenib 960 mg orally twice daily. [39]

Patients median survival with atezolizumab (Atezo) for treatment of non small cell lung cancer in the first line, IMpower 110 comparing Atezo to chemotherapy, IMpower 130 comparing Atezo+chemotherapy to chemotherapy, and IMpower150 comparing Atezo+chemotherapy+bevacizumab versus chemotherapy+bevacizumab. Adapted from: First line Immunotherapy for Non-Small Cell Lung Cancer. Nicola J. Nasser, Miguel Gorenberg, Abed Agbarya. Pharmaceuticals (Basel). 2020 Nov 8;13(11):373. https://doi.org/10.3390/ph13110373 Atezolizumab for treatment of non small cell lung cancer in the first line, IMpower 110, 130 and 150 studies.jpg
Patients median survival with atezolizumab (Atezo) for treatment of non small cell lung cancer in the first line, IMpower 110 comparing Atezo to chemotherapy, IMpower 130 comparing Atezo+chemotherapy to chemotherapy, and IMpower150 comparing Atezo+chemotherapy+bevacizumab versus chemotherapy+bevacizumab. Adapted from: First line Immunotherapy for Non-Small Cell Lung Cancer. Nicola J. Nasser, Miguel Gorenberg, Abed Agbarya. Pharmaceuticals (Basel). 2020 Nov 8;13(11):373. https://doi.org/10.3390/ph13110373

IMpower110 randomized patients with stage IV NSCLC with PD-L1 expression ≥ 1% to atezolizumab single agent or to chemotherapy. [19] The chemotherapy used was Cisplatin or Carboplatin, combined with gemcitabine for patient with squamous cell NSCLC, or pemetrexed for patients with nonsquamous disease. [19] Atezolizumab was better tolerated than chemotherapy. In the subgroup of patients with EGFR and ALK wild-type tumors who had PD-L1 stained ≥ 50% of tumor cells (205 patients), the overall survival was 20.2 months with atezolizumab, and 13.1 months with chemotherapy. [19] FDA approval is for patients with PD-L1 stained ≥ 50% of tumor cells, or PD-L1 stained tumor-infiltrating immune cells covering ≥ 10% of the tumor area, with no EGFR or ALK genomic tumor aberrations. [19]

IMpower130 was an open-label, phase III trial that compared atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy, with chemotherapy alone as first-line treatment for metastatic non-squamous NSCLC. [19] About half of the patients had PD-L1 negative tumors. Median overall survival was 18.6 months in the atezolizumab plus chemotherapy group and 13.9 months in the chemotherapy group; HR 0.79, p = 0.033. [19] Subgroup analysis showed progression free survival benefit, and a trend toward overall survival benefit in all PD-L1 expression levels. [19]

IMpower150 randomized patients with NSq NSCLC to treatment with chemotherapy plus bevacizumab, chemotherapy plus atezolizumab or chemotherapy plus bevacizumab and atezolizumab. [40] [19] The chemotherapy used was carboplatin and paclitaxel. [19] Median overall survival was 19.8 and 14.9 months for patients treated with chemotherapy plus bevacizumab, with or without atezolizumab, respectively. [19] Median OS with atezolizumab and chemotherapy alone was 19.5 months, raising question with regard to the added value of Bevacizumab to this combination for the general patients population. [19] Importantly, patients with baseline liver metastases had an improved overall survival with atezolizumab, bevacizumab, and chemotherapy combination, compared to bevacizumab and chemotherapy alone, with a median OS of 13.3 and 9.4 months, respectively, HR 0.52. [19] No improvement in overall survival was observed for patients with liver metastasis treated with chemotherapy and atezolizumab compared to patients treated with chemotherapy and bevacizumab. [19] Recent report about safety and patient-reported outcomes of atezolizumab plus chemotherapy and bevacizumab shows that this drug combination seems tolerable and with manageable toxicities. [41] [19] For patients with NSq NSCLC with baseline liver metastases, the combination of chemotherapy, atezolizumab and bevacizumab could be an option to consider in the first line. [19]

In August 2023, Great Britain's Healthcare Products Regulatory Agency (MHRA) approved subcutaneous atezolizumab for all indications in which the intravenous formulation of the drug has been approved, including select types of lung, bladder, breast, and liver cancers. After receiving approval NHS England stated that hundreds of patients who were treated with the immunotherapy, are set to receive "under the skin" injections of atezolizumab, which will eventually lead to more time for cancer teams. [42]

In January 2024, the European Commission granted marketing authorisation for Tecentriq® SC (atezolizumab), as the first PD-(L)1 cancer immunotherapy for subcutaneous (under the skin) injection in the European Union. [43]

Society and culture

Economics

Atezolizumab treatment costs on average US$13,200 per month in the United States, depending on the dosage schedule. [44] Despite updated data showing 30% more people with extensive stage small cell lung cancer have survived at 24 months, compared to those who received chemotherapy alone, [45] Canadian regulators had rejected funding for atezolizumab to treat extensive stage small-cell lung cancer "as too costly" followed by United Kingdom also citing "drug's cost-effectiveness." [46] [47] However, U.K. reversed its previous decision and approved Tecentriq for extensive stage small cell lung cancer after price reconsideration on 27 May 2020. [48] [49]

Research

As of 2016, it is in clinical trials for colorectal cancer, melanoma, breast cancer, non-small-cell lung carcinoma, bladder cancer, renal cell carcinoma. [50] [51] [ needs update ]

Promising results have been observed for melanoma and non-small-cell lung cancer, [52] and bladder cancer. [13]

A phase I trial reported a 19% objective response rate in metastatic triple-negative breast cancer. [53]

As of 2019, atezolizumab is in trial for several types of cancer, such as pancreatic cancer, gastric cancer and ovarian Cancer. [54] [ needs update ]

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References

  1. 1 2 "Tecentriq PI" (PDF).
  2. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 9 April 2023.
  3. ↑ "Prescription medicines and biologicals: TGA annual summary 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 31 March 2024.
  4. ↑ "Regulatory Decision Summary for Tecentriq / Tecentriq SC". Drug and Health Products Portal. 13 March 2024. Retrieved 1 April 2024.
  5. ↑ "Details for: Tecentriq". Drug and Health Products Portal. 2 May 2017. Retrieved 1 April 2024.
  6. ↑ "Details for: Tecentriq SC". Drug and Health Products Portal. 13 March 2024. Retrieved 1 April 2024.
  7. ↑ "Cancer therapies". Health Canada . 8 May 2018. Retrieved 13 April 2024.
  8. ↑ "Tecentriq 1,200 mg concentrate for solution for infusion - Summary of Product Characteristics (SmPC)". (emc). Retrieved 4 March 2020.
  9. 1 2 3 "Tecentriq- atezolizumab injection, solution". DailyMed. 3 June 2020. Retrieved 31 July 2020.
  10. 1 2 3 4 5 "Tecentriq EPAR". European Medicines Agency. 29 September 2017. Retrieved 31 July 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  11. ↑ "FDA grants approval to atezolizumab for alveolar soft part sarcoma". U.S. Food and Drug Administration (FDA). 9 December 2022. Retrieved 20 December 2022.
  12. 1 2 Madhusoodanan, Jyoti (9 August 2023). "How a controversial US drug policy could be harming cancer patients worldwide". Nature. 620 (7973): 264. Bibcode:2023Natur.620..264M. doi:10.1038/d41586-023-02492-x. PMID   37558845 . Retrieved 21 August 2023.
  13. 1 2 3 4 "Genentech Presents Positive Results of Atezolizumab in Advanced Bladder Cancer". 2 October 2015.
  14. 1 2 3 4 5 "FDA approves new, targeted treatment for bladder cancer" (Press release). U.S. Food and Drug Administration (FDA). 18 May 2016. Retrieved 20 May 2016.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  15. ↑ "European Commission approves Roche's Tecentriq SC, the EU's first PD-(L)1 cancer immunotherapy subcutaneous injection for multiple cancer types – Company Announcement - FT.com". markets.ft.com. Retrieved 5 March 2024.
  16. ↑ "FDA approves atezolizumab as adjuvant treatment for non-small cell lung cancer". U.S. Food and Drug Administration (FDA). 15 October 2021. Retrieved 15 October 2021.
  17. ↑ "Roche pulls Tecentriq in bladder cancer, completing sweep of 'dangling' accelerated approvals". BioPharma Dive. Retrieved 7 December 2022.
  18. ↑ FDA Professional Drug Information for Tecentriq.
  19. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Nasser NJ, Gorenberg M, Agbarya A (November 2020). "First line Immunotherapy for Non-Small Cell Lung Cancer". Pharmaceuticals. 13 (11): 373. doi: 10.3390/ph13110373 . PMC   7695295 . PMID   33171686. CC-BY icon.svg Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
  20. 1 2 3 4 Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet. Oncology. 18 (12): e731–e741. doi:10.1016/s1470-2045(17)30607-1. PMID   29208439.
  21. ↑ Shields M (11 April 2016). "Roche says FDA fast tracks atezolizumab in specific type of lung cancer". Reuters . Retrieved 11 April 2016.
  22. ↑ "Tecentriq (atezolizumab) Injection". U.S. Food and Drug Administration (FDA). 21 June 2016. Archived from the original on 5 December 2019. Retrieved 4 December 2019.
  23. ↑ "Failed confirmatory trial raises questions about atezolizumab for advanced urothelial cancer". HemOnc Today. 25 June 2017.
  24. ↑ "Checkpoint Inhibitor Use Changed for Bladder Cancer". National Cancer Institute. 26 July 2018.
  25. 1 2 "Atezolizumab for Urothelial Carcinoma". U.S. Food and Drug Administration. 18 May 2016. Retrieved 31 July 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  26. ↑ "Roche's shocking Tecentriq fail raises red flag for bladder cancer rivals". Fierce Pharma. 10 May 2017. Retrieved 11 May 2017.
  27. 1 2 "Drug Trials Snapshots: Tecentriq". U.S. Food and Drug Administration (FDA). 18 May 2016. Retrieved 31 July 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  28. 1 2 3 4 "FDA approves new treatment for non-small cell lung cancer". U.S. Food and Drug Administration (FDA). 18 October 2016. Retrieved 18 May 2016.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  29. ↑ McKee S (8 May 2018). "First-line use of Roche's Tecentriq given priority review". PharmaTimes. Retrieved 8 May 2018.
  30. ↑ "FDA updates prescribing information for Keytruda and Tecentriq". U.S. Food and Drug Administration. 16 August 2018. Retrieved 31 July 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  31. ↑ Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. (November 2018). "Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer". The New England Journal of Medicine. 379 (22): 2108–2121. doi: 10.1056/nejmoa1809615 . PMID   30345906.
  32. 1 2 "FDA approves atezolizumab with chemotherapy and bevacizumab for first-". U.S. Food and Drug Administration (FDA). 6 December 2018. Retrieved 4 March 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  33. ↑ "Roche scores first U.S. approval of immunotherapy for breast cancer". Stat . 9 March 2019. Retrieved 9 March 2019.
  34. 1 2 3 "FDA approves atezolizumab for PD-L1 positive unresectable locally advanced or metastatic triple-negative breast cancer". U.S. Food and Drug Administration (FDA) (Press release). 18 March 2019. Archived from the original on 5 December 2019. Retrieved 4 December 2019.
  35. 1 2 "FDA approves atezolizumab for extensive-stage small cell lung cancer". U.S. Food and Drug Administration (FDA). 19 March 2019. Archived from the original on 5 December 2019. Retrieved 5 December 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  36. 1 2 3 "FDA approves atezolizumab with nab-paclitaxel and carboplatin for metastatic NSCLC without EGFR/ALK aberrations". U.S. Food and Drug Administration (FDA) (Press release). 3 December 2019. Retrieved 31 July 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  37. 1 2 3 "FDA approves atezolizumab for first-line treatment of metastatic NSCLC with high PD-L1 expression". U.S. Food and Drug Administration (FDA). 18 May 2020. Retrieved 31 July 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  38. 1 2 3 "FDA approves atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma". U.S. Food and Drug Administration (FDA). 29 May 2020. Retrieved 31 July 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  39. 1 2 3 "FDA approves atezolizumab for BRAF V600 unresectable or metastatic melanoma". U.S. Food and Drug Administration (Press release). 30 July 2020. Retrieved 31 July 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  40. ↑ Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, et al. (June 2018). "Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC". The New England Journal of Medicine. 378 (24): 2288–2301. doi: 10.1056/NEJMoa1716948 . hdl: 10553/41871 . PMID   29863955.
  41. ↑ Reck M, Wehler T, Orlandi F, Nogami N, Barone C, Moro-Sibilot D, et al. (August 2020). "Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non-Small-Cell Lung Cancer". Journal of Clinical Oncology. 38 (22): 2530–2542. doi:10.1200/JCO.19.03158. PMC   7392741 . PMID   32459597.
  42. ↑ "Subcutaneous Atezolizumab Approved in Great Britain for All Intravenous Indications". OncLive. 29 August 2023. Retrieved 11 September 2023.
  43. ↑ "European Commission approves Roche's Tecentriq SC, the EU's first PD-(L)1 cancer immunotherapy subcutaneous injection for multiple cancer types". www.roche.com. Retrieved 5 March 2024.
  44. ↑ "What is the cost of Tecentriq?". Drugs.com.
  45. ↑ "SCLC". Tecentriq. Retrieved 4 March 2020.
  46. ↑ Martell A (20 February 2020). "Exclusive: Canadian regulator considers changes to new drug pricing plan". Reuters. Retrieved 4 March 2020.
  47. ↑ "NICE Cites Cost in Deciding Against Atezolizumab for Frontline Advanced Small Cell Lung Cancer" . OncLive. 6 January 2020. Retrieved 4 March 2020.
  48. ↑ "NICE recommends treatment for type of small-cell lung cancer". 27 May 2020.
  49. ↑ "NICE recommends Roche's Tecentriq in ES-SCLC following price rethink". 27 May 2020.
  50. ↑ "Search of: MPDL3280A". ClinialTrialsGov.
  51. ↑ Bendell JC, Kim TW, Goh BC, Wallin J, Oh DY, Han SW, et al. Clinical activity and safety of cobimetinib (cobi) and atezolizumab in colorectal cancer (CRC). 2016 ASCO Annual Meeting.
  52. ↑ Facchinetti F, Bordi P, Leonetti A, Buti S, Tiseo M (10 September 2018). "Profile of atezolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives". Drug Design, Development and Therapy. 12: 2857–2873. doi: 10.2147/DDDT.S124380 . PMC   6137949 . PMID   30237696.
  53. ↑ "MPDL3280A Shows Activity in Triple-Negative Breast Cancer". Cancer Network. 20 April 2015.
  54. ↑ "Product Development Portfolio". Roche. Archived from the original on 28 April 2021. Retrieved 27 February 2019.

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