Roche...announced that the European Commission has approved Tecentriq® (atezolizumab) as an adjuvant treatment, following complete resection and platinum-based chemotherapy, for adults with non-small cell lung cancer (NSCLC) with a high risk of recurrence* whose tumours express PD-L1≥50% and who do not have EGFR mutant or ALK-positive NSCLC.

Roche...today announced that the European Commission has approved Tecentriq® (atezolizumab) as a first-line (initial) treatment for adults with metastatic non-small cell lung cancer (NSCLC) whose tumours have high PD-L1 expression, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumour aberrations.

...Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced today that it has obtained regulatory approval for its humanized anti-PD-L1 monoclonal antibody, Tecentriq® Intravenous Infusion 1200 mg [generic name: atezolizumab (genetical recombination)] from the Ministry of Health, Labour and Welfare (MHLW) for additional dosing for the treatment of chemotherapy-naïve PD-L1-positive unresectable advanced or recurrent non-small cell lung cancer (NSCLC)....This approval is based on the results from the phase III IMpower110 study. The study met its primary endpoint in an interim analysis showing that Tecentriq monotherapy improved overall survival (OS) by 7.1 months compared with chemotherapy alone in patients with high PD-L1 expression...

TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: Non-Small Cell Lung Cancer (NSCLC)....in combination with paclitaxel protein-bound for the treatment of adult patients 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.

Atezolizumab is recommended, within its marketing authorisation, as an option for untreated metastatic non-small-cell lung cancer (NSCLC) in adults if...their tumours have PD-L1 expression on at least 50% of tumour cells or 10% of tumour-infiltrating immune cells....Pembrolizumab in combination with chemotherapy may also be offered.

Atezolizumab is recommended, within its marketing authorisation, as an option for untreated metastatic non-small-cell lung cancer (NSCLC) in adults if...their tumours have PD-L1 expression on at least 50% of tumour cells or 10% of tumour-infiltrating immune cells

PD-L1 expression positive (≥50%)…Adenocarcinoma, large cell, NSCLC NOS…other recommended…Carboplatin + albumin-bound paclitaxel + atezolizumab

Atezolizumab monotherapy is recommended as a first-line therapy option for patients with metastatic NSCLC, PD-L1 levels of 50% or more, and negative test results for EGFR, ALK, ROS1, METex14 skipping, RET, or BRAF variants, regardless of histology...

Atezolizumab is associated with better efficacy outcomes and provided LTB in a higher number of patients compared to chemotherapy in the ever-smoking PD-L1 high population.

The design, participants, and primary-endpoint DFS outcomes have been reported for this phase 3, open-label, 1:1 randomised study of atezolizumab (1200 mg q3w; 16 cycles) vs BSC after adjuvant platinum-based chemotherapy (1-4 cycles) in adults with completely resected stage IB (≥4 cm)-IIIA NSCLC....Although OS remains immature for the ITT population, these data indicate a positive trend favouring atezolizumab in PD-L1 subgroup analyses, primarily driven by the PD-L1 TC ≥50% stage II-IIIA subgroup.

In PD-L1-high disease, atezolizumab provided a clinically meaningful improvement, reducing the risk of death by 57 percent (≥50%; HR=0.43, 95% CI: 0.24-0.78), compared with BSC.

Roche...announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Tecentriq® (atezolizumab) as an adjuvant treatment, following complete resection and platinum-based chemotherapy, for adults with non-small cell lung cancer (NSCLC) with a high risk of recurrence whose tumours express PD-L1≥50% and who do not have EGFR mutant or ALK-positive NSCLC....The recommendation from the CHMP is based on results from the DFS interim analysis of the Phase III IMpower010 study.

...atezolizumab versus docetaxel by programmed death-ligand 1 (PD-L1) status, in patients with previously treated metastatic NSCLC....In the 22C3-BEP, overall survival (OS) benefits with atezolizumab versus docetaxel were observed across PD-L1 subgroups; benefits were greatest in SP142-defined PD-L1–high (TC3 or IC3: HR 0.39; 95% CI, 0.25-0.63) and 22C3-defined PD-L1–high (TPS ≥50%: HR 0.56, 95% CI, 0.38-0.82) and –low (TPS 1%-<50%: HR 0.55; 95% CI, 0.37-0.82) groups. Progression-free survival (PFS) improved with increasing PD-L1 expression for both assays.

Roche...today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Tecentriq® (atezolizumab) as a first-line (initial) treatment for adults with metastatic non-small cell lung cancer (NSCLC) whose tumours have high PD-L1 expression...

In the subgroup of patients with EGFR and ALK wild-type tumors who had the highest expression of PD-L1 (205 patients), the median overall survival was longer by 7.1 months in the atezolizumab group than in the chemotherapy group (20.2 months vs. 13.1 months; hazard ratio for death, 0.59; P=0.01)....Atezolizumab treatment resulted in significantly longer overall survival than platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression...

OS and PFS in the PD-L1–high (TC3 or IC3; ≥ 50% TPS; ≥ 50% TC) subgroups favoured atezo (OS data shown in table).

In the first-line setting, the most effective treatments for patients with PD-L1 expressions of ≥50%, 1-49%, and <1% were atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab, respectively.

...Patients with EGFR activating mutations or ALK- positive tumour mutations should also have received targeted therapy (Cohort 3 LOT1 NSCLC) or (4) In combination with carboplatin and etoposide, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) (Cohort 4 LOT1 ES-SCLC) or (5) As a monotherapy, for the treatment of metastatic NSCLC with high PD-L1 expression, previously untreated (Cohort 5 LOT1 NSCLC) or (6) In combination with bevacizumab for unresectable locally advanced or metastatic hepatocellular carcinoma previously untreated with systemic therapy (Cohort 6 LOT1 HCC) ....

The median OS (months) in the Atezo, Doce, and Doce+Ram groups were 17.5, 7.6, and 11.5, respectively; and were 29.5, 7.2, and 6.9, respectively in the PD-L1 > 50% subgroups. The Atezo group showed significantly greater OS improvement compared with the Doce group (HR 0.42, 95% CI 0.26 – 0.66, p = 0.001**). This benefit appears greater and remains statistically significant in the PD-L1 > 1% (HR 0.39, 95% CI 0.22 – 0.71, p = 0.005**) and PD-L1 > 50% (HR 0.37, 95% CI 0.15 – 0.91, p = 0.022*) subgroups....We observed statistically significant and clinically meaningful PFS and OS benefits of atezolizumab monotherapy compared with docetaxel in patients with advanced NSCLC who were pretreated with IO. The OS benefits of atezolizumab over docetaxel +/- ramucirumab was greater in PD-L1 > 1% and PD-L1 > 50% subgroups.

In 229 pts with stage II-IIIA PD-L1 TC ≥50% NSCLC, the OS HR was 0.43 (95% CI: 0.24, 0.78); after excluding 20 pts with known EGFR/ALK+ status, the OS HR was 0.42 (95% CI: 0.23, 0.78). The OS subgroup analysis is presented in the table….Pts with stage II-IIIA PD-L1 TC ≥50% NSCLC derived OS benefit with atezo vs BSC. OS benefit was consistent across most pt subgroups, albeit with limited numbers in this exploratory analysis. The atezo safety profile remained unchanged.

DFS in PD-L1 TC >/= 50% (VENTANA SP263 assay) stage II-IIIA (UICC/AJCC v7) pts was a prespecified secondary endpoint....Median follow-up was 34.2 mo (21 Jan 2021 cutoff). See the table for DFS subgroup data. Safety in PD-L1 TC >/= 50% stage II-IIIA pts was consistent with that of the overall study population and known safety profile of atezo….IMpower010 pts with PD-L1 TC >/= 50% stage II-IIIA NSCLC derived DFS benefit with atezo vs BSC at the interim DFS analysis....The tolerability profile of atezo was in line with the overall population, demonstrating a positive benefit-risk profile.

...high PD-1 expression was detected in all patients' peripheral CD8+ T cells before the treatment of atezolizumab....confirmed the existence of CD8+ PD-1high T cells with an exhaustion phenotype in Chinese NSCLC patients....study demonstrated that efficient anti-PD-L1 therapy could reshape the TCR repertoire for antitumor patients.

Importantly, for PDL1 high patients without KEAP1, EPHA5, TP53 mutations receiving atezolizumab, they all showed relatively longer median survival with 22.47, 22.18 and 23.33 months, respectively (all, P < 0.01).

In case of PD-L1-expression > 50 %, ECOG status of 0 or 1 and expected operability, patients received ICI….All four patients underwent therapy with two to six cycles of ICI (3 × pembrolizumab, 1 × atezolizumab) without any complication, and ICI did not delay the time of surgical resection….In selected patients, neoadjuvant therapy with ICI is well tolerated and can induce a complete remission of the tumor.

In the patient arm that received Atezo at T0, PD-L1 expression in CStCs was low in 21 pts and high in 17 pts, with no relationship to PFS (HR=0.5, 95%CI 0.2-1.7, p=0.18) or OS (HR=1.6, 95%CI 0.4-6.0, p=0.75). However at T1, pts with high PD-L1 had significantly improved PFS response to Atezo (HR 5.4, 95%CI 1.7-17.0, p=0.009), and improved OS (HR 21.5, 95%CI 4.5-91.9, p<0.001).

In the PD-L1-high patients again the combination of chemotherapy with atezolizumab or pembrolizumab, exhibit significant PFS benefit, followed by pembrolizumab-monotherapy... The combination of chemotherapy with either pembrolizumab or atezolizumab show consistently higher efficacy than chemotherapy-alone or any other ICI-combination or monotherapy, particularly in non-squamous patients.