TNBC patients (n = 54) enrolled in this phase 1a trial (Emens et al., 2015) with a dose escalation and expansion cohort. Gli altri ingredienti sono L-istidina, acido acetico glaciale, … How effective is atezolizumab (Tecentriq)? The incidence of treatment discontinuation was 8% with atezolizumab versus 22% with docetaxel. Fever 7. Diarrhea 6. There was not a significant difference between atezolizumab and docetaxel in terms of PFS (median 4.0 months vs. 2.8 months, respectively) or response rate (14% vs. 13%), although duration of response strongly favored atezolizumab (16.3 months vs. 6.2 months). There is a general impression that anti-PD-L1 antibodies are less toxic then anti-PD-1 antibodies. Sixty-nine percent of patients enrolled were PD-L1 diagnostic-positive. Patients’ median age was 53 years (range, 29–82 years), they had an ECOG PS of 0 (48%) or 1 (50%), they were exposed to > 4 systemic therapies (89%), and they had received prior therapy with either an anthracycline- (85%), a taxane- (74%), or a platinum-based chemotherapy (57%). In fact, blocking PDL1 resulted in a loss of regulatory function and reduction in fetal survival rate.”, The term “Tregs,” which is pronounced “tee-regs,”242 refers to T-regulatory cells. FDA referred to articles in the scientific literature, revealing that one of the goals of the PD-L1 to PD-1 signaling pathway in normal physiology is to prevent the mother from mounting an immune response against the fetus and to prevent the mother’s immune system from killing the fetus. The most common Grade 3 to 4 adverse reactions (greater than 2%) were urinary tract infection, anemia, fatigue, dehydration, intestinal obstruction, urinary obstruction, hematuria, dyspnea, acute kidney injury, abdominal pain, venous thromboembolism, sepsis, and pneumonia. provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. The Use in Specific Populations section referred to mechanism of action and to animal toxicity studies: USE IN SPECIFIC POPULATIONS … Animal reproduction studies have not been conducted with TECENTRIQ to evaluate its effect on reproduction and fetal development. Atezolizumab, the most recently approved anti-PDL-1 antibody was studied as a single agent in patients with locally advanced and metastatic urothelial carcinoma. Atezolizumab was well tolerated with 13% of patients experiencing grade 3–4 toxicities. Reviewer note: Pneumonitis is a known toxicity from anti-PD-1 and anti-PD-L1 drugs. Immune-Related Pneumonitis: Withhold for moderate and permanently discontinue for severe or life-threatening pneumonitis … Immune-Related Hepatitis: Monitor for changes in liver function. Porter et al. There was no measurable certolizumab pegol binding affinity.”, FDA’s Pharmacology Review warned against risk of atezolizumab to the fetus: “Atezolizumab maintains binding to the FcRn receptor, so fetal exposure may occur if a patient is treated during pregnancy … [i]t is unclear whether fetal exposure to atezolizumab would occur at levels sufficient to cause adverse effects on the developing immune system [of the fetus] … there is a … risk of developing immune-mediated disorders … in the offspring due to the mechanism of action.”246, FDA then turned its attention to the package label and made recommendations regarding pregnancy as well as for lactation and breast feeding. In Summary. Two PRs were observed in the PD-L1 IHC IC2 group. It is used with paclitaxel albumin-stabilized nanoparticle formulation in adults whose cancer is locally advanced, metastatic, or cannot be removed by surgery.¹ 2. No.”, “Is the drug a substrate of CYP enzymes? A randomized phase II study compared atezolizumab 1200 mg with docetaxel 75 mg/m2, both given in a 21-day cycle. Is atezolizumab (Tecentriq) a chemotherapy or immunotherapy drug? Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them: Common (1% to 10%): Venous thromboembolism[Ref], Very common (10% or more): Rash (15%), pruritus (13%)[Ref], Frequency not reported: Immune-related thyroid disorders (e.g., hyperthyroidism, hypothyroidism)[Ref], Very common (10% or more): Nausea (25%), constipation (21%), diarrhea (18%), abdominal pain (17%), vomiting (17%), Common (1% to 10%): Dehydration, intestinal obstruction[Ref], The most common adverse reactions (greater than 20%) were fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation. But unfortunately, releasing the inhibitions also increases inflammation and autoimmunity in various tissues and organs in the body. Cerner Multum, Inc. "UK Summary of Product Characteristics." Atezolizumab è un anticorpo monoclonale umanizzato IgG1 ingegnerizzato Fc diretto contro il ligando 1 (L1) del recettore di morte cellulare programmata (Programmed cell Death, PD) ed è prodotto in cellule … Atezolizumab was first evaluated in a phase I study that included patients with advanced incurable cancer, including NSCLC, melanoma, renal cell carcinoma, colorectal cancer, gastric cancer, and head and neck squamous cell carcinoma. FDA’s narratives on pregnancy, lactation, and breast-feeding found a place on the package label, as shown below. This was included to be consistent with labels for FDA-approved products inhibiting PD-1 … the Division recommends that females … should use effective contraception during treatment.”247. Responses were evaluated in the context of PDL1 expression (based on an assay using the Sp142 antibody on a VENTANA platform) on TCs and immune cells (ICs). For use in animal studies, the Sponsor prepared a specially engineered version of atezolizumab consisting of the constant region of mouse IgG2a plus the variable region (PD-L1 binding region) of the humanized antibody. Last updated on Jan 18, 2020. Atezolizumab is the generic name for the trade drug name Tecentriq™. There may be benefits to targeting PDL1 rather than PD1 as this spares interruption of PDL2–PD1 interactions and therefore theoretically may have fewer side effects. Atezolizumab agisce come immunomodulatore, bloccando il ligando della proteina della morte cellulare, nello specifico l’interazione fra PD-L1 e PD-1 Boves (Cuneo) via Roncaia, 123 12012 , 348-6955350 Dopo diluizione (vedere paragrafo 6.6), la concentrazione finale della soluzione diluita deve essere tra 3,2 e 16,8 mg/mL. He received prednisone for possible autoimmune hepatitis and his liver enzymes and encephalopathy resolved by days 42 and 47 respectively. Among 275 patients…114 patients (41.5%) tested positive for treatment-emergent…anti-therapeutic antibodies…at one or more post-dose time points…the presence of anti-therapeutic antibodies did not appear to have a clinically significant impact on pharmacokinetics, safety or efficacy.78, Rina Hui MBBS, PhD, Michael Millward MBBS, MA, in Pulmonary Adenocarcinoma: Approaches to Treatment, 2019, Another biomarker was also investigated in several atezolizumab studies. FDA’s observations on immune-related AEs with atezolizumab found a place on the package label for atezolizumab (Tecentriq®): WARNINGS AND PRECAUTIONS. In the subset of patients with nonsquamous histology, survival was 15.5 months with atezolizumab (95 patients) and 10.9 months with docetaxel (95 patients). Ai pazienti trattati con KEYTRUDA deve essere consegnatala Scheda di Allerta per il Pazientee devono essere date informazionisui rischi di KEYTRUDA (vedere anche il foglio illustrativo). Treatment-related adverse events, grade 3 or higher, were noted in 15% of patients receiving atezolizumab and 43% of patients receiving docetaxel. Bevacizumab 15 mg/kg IV on Day 1 . The ORR was 15% in both the atezolizumab and docetaxel groups, but the response was more durable with atezolizumab, with median duration of 14.3 months (95% CI 11.6-nonestimable) compared with 7.2 months with docetaxel (5.6–12.5 months). Pneumonitis (any grade) developed in nine patients (3%); grade 3 or grade 4 pneumonitis developed in three (1%). No cases of grade 3–5 pneumonitis was observed. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Six patients (1.9%) developed pneumonitis … [t]he median day of onset for the first event for these six patients was day 81 (range: 14-127) … [f]ive of these patients were treated with corticosteroids.124”. Consistent with the above studies, the safety profile favored atezolizumab. [Ref], Very common (10% or more): Urinary tract infection (22%), Common (1% to 10%): Urinary obstruction[Ref], Common (1% to 10%): Anemia, lymphopenia, increased alkaline phosphatase, increased alkaline phosphatase[Ref], Common (1% to 10%): Acute kidney injury, liver enzyme increase, increased ALT, increased AST, Very common (10% or more): Immune related colitis (19.7%), Common (1% to 10%): Immune related pneumonitis, immune related hepatitis, sepsis, Frequency not reported: Immune related endocrinopathies[Ref], Frequency not reported: Infusion related reactions[Ref], Very common (10% or more): Decreased appetite (26%), Common (1% to 10%): Hyponatremia, hyperglycemia, hypoalbuminemia[Ref], Very common (10% or more): Back/neck pain (15%), arthralgia (14%)[Ref], Frequency not reported: Meningoencephalitis, myasthenic syndrome/myasthenia gravis, Guillain-Barre[Ref], Frequency not reported: Ocular inflammatory toxicity[Ref], Very common (10% or more): Fatigue (52%), pyrexia (21%), peripheral edema (18%), Common (1% to 10%): Increased creatinine[Ref], Common (1% to 10%): Confusional state[Ref], Very common (10% or more): Dyspnea (16%), cough (14%), Common (1% to 10%): Dyspnea, pneumonia[Ref], 1. An Infection 3. Drug Type: Atezolizumab … In caso di polmonite di grado 3 o 4, il trattamento con atezolizumab … Thus, it is plausible that this patient’s death was attributable to toxicity from the study drug.122, Subileus Patient 8013. FDA cited D’Addio et al.239 and Taglauer et al.240 who describe the mechanism for preventing harm to the fetus. Patients with nonsquamous histology also had an improved survival with atezolizumab (HR 0.73, 95% CI 0.60–0.89). Fifty-seven patients (18.3%) received systemic corticosteroids within 30 days of an adverse event … [t]wenty of these patients (6.4%) were considered to have experienced an immunological AE … [o]ne patient died from subileus, which was considered to be an immunological AE.127”, The importance of correlating corticosteroid use with immune-related AEs, as a means for identifying safety signals, is highlighted by the fact that FDA’s Cross Discipline Team Leader Review observation that, “Adverse events that were likely to be immune-mediated and were treated with corticosteroids occurred in 6% of patients.128”. The design of the atezolizumab clinical trial excluded subjects already suffering from autoimmune disorders. Popolazioni … Sub-ileus and volvulus are types of intestinal obstruction.120 FDA’s review for atezolizumab defined sub-ileus as an immunological AE.121 Regarding inflammatory disorders caused by the study drug, FDA’s Medical Review stated: Pneumonitis Patient 1087. Package label. This approach was to identify subjects receiving antiinflammatory drugs (hydrocortisone, dexamethasone, and cortisone). Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Blockage of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to a fetus and to result in … fetal loss, therefore … risks of administering TECENTRIQ during pregnancy include … abortion or stillbirth.249. This … provides evidence that atezolizumab can cause fetal harm … to a pregnant woman.”238. The Warnings and Precautions section of the package label for atezolizumab (Tecentriq®) warned against harm to the fetus. Patients were scored depending on PD-L1 expression on tumor-infiltrating immune cells by IHC as PD-L1 IC 0, 1, 2, 3. Survival favored atezolizumab with a median survival of 12.6 months with atezolizumab and 9.7 months with docetaxel (HR 0.73, 95% CI 0.53–0.99). Grade 1 or grade 2 pneumonitis developed in four patients (3%). 1 ALLEGATO I RIASSUNTO DELLE CARATTERISTICHE DEL PRODOTTO Documento reso disponibile da AIFA il 11/12/2020 Esula dalla competenza dell’AIFA ogni eventuale disputa concernente i diritti di … This warning was based on the mechanism of action of the drug and on animal toxicity studies: WARNINGS AND PRECAUTIONS. In a phase I study, atezolizumab demonstrated responses across several tumor types including a response rate of 23% in 53 patients with NSCLC and 21% in the 42 patients with nonsquamous histology.49 There was an association between response and expression of PD-L1, although the assay used to assess PD-L1 expression was different from the ones used above. Reviewer note: Anti-PD-1/PD-L1 drugs can induce colitis, which may plausibly predispose to volvulus. Subjects receiving hydrocortisone can be detected with absolute certainty whereas, in contrast, a Case Report Form with the notation, “patient has rash,” is relatively ambiguous. D’Addio et al.241 inform us that “Acceptance of the … fetus by the mother during pregnancy represents a physiologic model of in vivo immune tolerance … [o]ur group has … shown that the PD1-PDL1 … pathway plays a key role in inducing and maintaining fetomaternal tolerance in a mouse model … expression of PDL1 on the surface of Tregs is essential to exert their suppressive effect and to control the maternal immune response. The drug prevents a protein called PD-L1 that is found on some tumour cells from binding to another … (atezolizumab) injection, for intravenous use Initial U.S. Approval: 2016 INDICATIONS AND USAGE TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated for the treatment of … As many as 14% of patients had grade 3 or grade 4 treatment-related adverse events, the most common of which was fatigue. The randomized phase III OAK study also compared atezolizumab 1200 mg with docetaxel 75 mg/m2 in patients with NSCLC (any histology, no PD-L1 expression required) who had received 1–2 prior chemotherapy regimens.50 This large study of 1225 patients had a primary endpoint of overall survival, and survival was improved with atezolizumab, in both the intention to treat population and in the PD-L1 expression subpopulations. Constipation 3. trattamento con atezolizumab può essere ripreso se l’evento registra un miglioramento a un grado ≤ 1 entro 12 settimane e la dose di corticosteroidi è stata ridotta a ≤ 10 mg/die di prednisone o equivalente. The PD-L1 to PD-1 signaling pathway is used by cancer cells to prevent CD8+ T-cells from killing cancer cells and to dampen the body’s immune response against the cancer. Leena Gandhi, ... Frances A. Shepherd, in IASLC Thoracic Oncology (Second Edition), 2018. Possibili effetti indesiderati di Atezolizumab Il principio attivo è atezolizumab. Package label. It is used: 1. In normal physiology, Tregs dampen immune responses in the body and prevent the immune system from inflicting damage on the body’s own tissues, that is, to prevent autoimmunity.243, Further addressing harm to the fetus, FDA observed that atezolizumab can bind to the FcRn receptor. He received prednisone with resolution of liver enzyme elevation by day 51.125, FDA’s Medical Review further described colitis, “Patient 1090 experienced Grade 2 microscopic colitis. Atezolizumab was first approved by … Aipazienti trattati con KEYTRUDA deve essere consegnatala scheda di allerta per il pazientee devono essere date informazionisui rischi di KEYTRUDA (vedere anche il foglio illustrativo). 2. Urinary … The FDA reviewer contemplated atezolizumab’s influence on CYP enzymes and on drug transporters, and dismissed these types of influences as being unlikely. Atezolizumab è indicato in monoterapia per il trattamento di pazienti adulti affetti da carcinoma polmonare non a piccole cellule localmente avanzato o metastatico precedentemente sottoposti a chemioterapia. FcRn receptor mediates transfer of antibodies across the placenta to the fetal bloodstream. warned that “The active transfer of … antibodies across the placenta by binding of the Fc-region to the neonatal Fc receptor (FcRn) may result in adverse fetal or neonatal effects.”244, Porter et al.245 describe this binding to neonatal Fc receptor: “Binding affinities of certolizumab pegol, infliximab, adalimumab and etanercept to human FcRn and FcRn-mediated transcytosis were determined using in vitro assays. Comments by FDA reviewers on AEs of individual patients included remarks attributing the AE to inflammation or autoimmunity and relatedness to the study drug. Atezolizumab 1200 mg IV on Day 1 (administered before bevacizumab), plus . Copyright © 2020 Elsevier B.V. or its licensors or contributors. Median overall survival was 13.8 months with atezolizumab and 9.6 months with docetaxel (HR 0.73, 95% CI 0.62–0.87). Treatment with atezolizumab was administered at 15 mg/kg, 20 mg/kg, or 1200 mg IV every 3 weeks for a median duration of 6 weeks (range, 0–85 weeks). PFS was 2.7 months with atezolizumab versus 3.0 months with docetaxel. James Chih-Hsin Yang, ... Chia-Yu Chu, in IASLC Thoracic Oncology (Second Edition), 2018, NSCLC is now known to be an immunologically targetable cancer. The Sponsor had conducted a drug class analysis based on the mechanism of action to predict AEs in humans. Atezolizumab was approved by the FDA on 10/18/16 for the treatment of NSCLC following platinum-based chemotherapy independent of PD-L1 expression. Atezolizumab is a recombinant humanized antibody that binds to PD-L1 and prevents binding of PD-L1 (ligand) to PD-1 (receptor). Ogni mL contiene 60 mg di atezolizumab. Applies to atezolizumab: intravenous solution. The data from meta-analysis shown in Table 11.7 confirms this impression. If experienced, these tend to have a Severe expression 1. Atezolizumab - Last updated on December 10, 2020 All rights owned and reserved by Memorial Sloan Kettering Cancer Center. Drug class analysis was used for arriving at this warning, as is evident from the writing, “This was included to be consistent with labels for FDA-approved products inhibiting PD-1.” FDA referred to other FDA-approved products that had the same mechanism of action as atezolizumab (blocking PD-L1 to PD-1 binding). Eleven percent of patients experienced a treatment-related Grade 3 AE. In adults whose disease has gotten worse during or after treatment with platinum chemotherapy. Atezolizumab was temporarily interrupted. When administered to a cancer patient, atezolizumab removes the naturally occurring inhibitions against immune response, that is, inhibitions imposed by PD-L1/PD-1 signaling. Repeat every 3 weeks until disease progression or unacceptable toxicity. Poiché atezolizumab viene eliminato dalla circolazione sanguigna mediante catabolismo, non si prevedono interazioni farmacologiche di tipo metabolico.... Vedi la Scheda Tecnica … Abnormal Sensations Of The Skin 2. Embryo-Fetal Toxicity. Does atezolizumab (Tecentriq) cause hair loss? Atezolizumab, a high affinity–specific humanized IgG1 antibody against PD-L1, is FDA approved for use in metastatic NSCLC after disease progression on platinum-containing chemotherapy. Patient 1115 developed AST/ALT on day 8 which worsened to Grade 3 by day 16. The study included 287 patients with a primary endpoint of overall survival. Tra gli effetti collaterali dell’atezolizumab c’ è anche la tosse, come riportato dalla scheda tecnica segnalata dall’agenzia del farmaco QUI LINKATA Ad ogni modo è fondamentale parlarne con il suo … A literature-based assessment of the effects on reproduction demonstrated that a … function of the PD-L1/PD-1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to a fetus. Un flaconcino da 14mL di concentrato contiene 840 mg di atezolizumab*. Enroled patientswill receive 1200 mg of atezolizumab and 15mg/Kg of Avastin® (bevacizumab) administered by IV … Atezolizumab, sold under the brand name Tecentriq, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small … Available for Android and iOS devices. Numbness And Tingling 11. Unlikely.”, “Metabolism studies are not generally performed for biological protein products. Drug class: anti-PD-1 monoclonal antibodies, general feeling of tiredness and weakness, ulcers, sores, or white spots in the mouth, difficulty with chewing, swallowing, or talking, sudden numbness and weakness in the arms and legs, Blistering, peeling, or loosening of the skin, pains in the stomach, side, or abdomen, possibly radiating to the back, red skin lesions, often with a purple center, swelling of the eyelids, face, lips, hands, or feet, weakness in the arms, hands, legs, or feet. On this point, FDA stated, “Corticosteroid use. Treatment-related adverse events of any grade were 67% with atezolizumab and 88% with docetaxel; 8% of patients in the atezolizumab group withdrew from the study because of adverse events versus 22% in the docetaxel group. There were additional delayed responses after RECIST-determined progressive disease. PD-L1 expression was quantified with the Ventana SP142 IHC assay and included expression of PD-L1 (with different cutoffs) on both tumor cells and tumor-infiltrating immune cells. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. In the subset of patients with any PD-L1 expression (on tumor cells or immune cells), survival favored atezolizumab with a median survival of 15.7 months compared with 10.3 months with docetaxel (HR 0.74, 95% CI 0.58–0.93). The result of the removed inhibitions is the desired consequence of enhanced immune response against cancer. The Use in Specific Populations section included a separate warning about lactation: USE IN SPECIFIC POPULATIONS … Lactation … There is no information regarding … atezolizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Atezolizumab is the generic name for a drug with the brand name Tecentriq ®. See below for a comprehensive list of adverse effects. In the PD-L1 low or undetectable cohort, survival still favored atezolizumab with a median survival of 12.6 months compared with 8.9 months (HR 0.75, 95% CI 0.59–0.96). "Product Information. Human placentas were perfused … to measure transfer of [antibodies] … from the maternal to fetal circulation. La dose è di 1200 mg. La somministrazione è endovenosa e si ripete ogni 21 giorni. Grade 3 or grade 4 immune-related adverse events occurred in 6% of patients, which mainly included diarrhea, rash, transaminitis, and thyroid abnormalities. L. de la Cruz-Merino, ... V. Sánchez-Margalet, in International Review of Cell and Molecular Biology, 2017. FDA’s Medical Review described this exclusion criterion as, “The trial excluded patients with a history of autoimmune disease with the exception of patients with a history of autoimmune hypothyroidism … and patients with … type 1 diabetes mellitus.119” Excluding this type of study subject prevented the obscuring of any autoimmune AEs arising from the study drug itself. Seventy percent of patients had visceral metastases at baseline and 24% had bone involvement. Commonly reported side effects of atezolizumab include: herpes simplex encephalitis, infection, mycobacterium infection, retroperitoneal hemorrhage, sepsis, severe infection, … Atezolizumab received a breakthrough therapy designation in 2015 for the treatment of PDL1 expression–positive NSCLC progressing after first-line chemotherapy. In some cases, health care professionals may use the generic name atezolizumab when referring to the trade drug name Tecentriq™. As proteins are degraded into amino acids that are subsequently recycled into other proteins, the classical biotransformation studies for small molecule drugs are not applicable.”. Ciascun flaconcino contiene 1.200 mg di atezolizumab (in 20 mL). FDA took a reasonable approach for identifying study subjects with AEs having an immune component. A total of 2 CRs were observed: 1 CR was observed in the PD-L1 IHC IC2 group and the other in the PD-L1 IHC IC3 group. The most common atezolizumab-related grade 3 events (there were no grade 4 events) were pneumonia (2%) and AST elevation (2%). Chemotherapy-naïve patients high-intermediate TMB (TMB≥10 mutations/MB) and with locally advanced or metastatic non-squamous non-small cell lung cancer patients will be selected. Log in to print or send this list to … FDA’s labeling recommendation took the form, “Labeling … the Division recommended that patients should not breastfeed during treatment … due to the potential for serious adverse reactions in breastfed infants from atezolizumab. The constant region (Fc region) of the antibody is what binds to FcRn receptor. Atezolizumab is an antibody that binds to PD-L1, thereby blocking the PD-L1/PD-1 signaling pathway. How is atezolizumab (Tecentriq) administered? As with all therapeutic proteins, there is a potential for immunogenicity. Nausea 10. FDA’s account of antiinflammatory drug use distinguished between cases where the AE was immune-related and where the AE was not immune-related. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab. Grade 3 or grade 4 immune-related adverse events occurred in 5.3% of patients, mainly thyroid abnormalities. Adding atezolizumab to chemotherapy and bevacizumab in patients with higher Teff signature expression was associated with bigger magnitude of PFS benefit (HR 0.51) than those with lower Teff signature (HR 0.76).42. Treatment discontinuation from adverse event occurred in 8% of patients receiving atezolizumab and 19% with docetaxel. Patient 1141 developed flu-like symptoms on day 2 and Grade 1 AST/ALT increases on day 13 followed by delirium on day 15. come da scheda tecnica KEYTRUDA in monoterapia è indicato nel trattamento del melanoma avanzato (non resecabile o metastatico) nei pazienti adulti (indicazione rimborsata). Decreased Appetite 5. Atezolizumab prevents cancer cells from using this tactic to evade the immune system. Scheda tecnica (RCP) Composizione: Un flaconcino da 20 mL di concentrato contiene 1.200 mg di atezolizumab*. Low Energy 9. In the PD-L1 diagnostic-positive efficacy cohort (IC2-3, n = 21), investigator-assessed confirmed ORR was 19% (95% CI, 5–42). Atezolizumab was resumed on day 163 and the colitis resolved by day 203.126”. There was a statistically significant improvement in response rate with higher PDL1 expression (p = 0.015) on ICs, but not with tumoral PDL1 expression (p = 0.920).84 A T-helper type 1 like gene signature was also associated with response. Other studies showed a similar toxicity profile as well [48,49].The other anti-PDL1 is Durvalumab, which has shown similar toxicity profile as well [50,51]. The ORR in patients with NSCLC was 21%, whereas ORR across all tumor types was 18%. Genentech, South San Francisco, CA. The patient’s death due to septic shock and respiratory failure, occurred in close temporal proximity to pneumonitis. In a phase I expansion study, pretreated patients with NSCLC were treated at doses of 1 mg/kg, 10 mg/kg, 15 mg/kg, or 20 mg/kg.83 An objective response was noted in 12 (23%) of 53 evaluable patients with NSCLC. Atezolizumab was withheld and no other treatment was reported. Higher expression of T-effector and interferon-γ gene signature (comprising CD8A, GZMA, GZMB, IFNγ, EOMES, CXCL9, CXCL10, TBX21 genes), reflecting preexisting immune competency, was associated with improved OS (HR 0.43) in patients treated with atezolizumab from the POPLAR study.61 Similarly in patients from the randomized OAK study, T-effector (Teff) signature (comprising three genes PD-L1, CXCL9, and IFNγ) >median was associated with superior PFS (HR 0.73) and OS (HR 0.59).68 With bigger magnitude of benefit and similar prevelance of Teff signature > median (50% of patients), Teff appears to be a more sensitive biomarker than PD-L1 expression in predicting benefit from atezolizumab.68 The clinical value of Teff signature was further evaluated prospectively in the IMPOWER 150 study.

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