Abstract

On October 29, 2021, the National Comprehensive CancerNetwork (NCCN) has updated the clinical diagnosis and treatment guidelines fornon-small cell lung cancer (NSCLC)for the second in less than one month.Compared with the 6th editionof the guidelines, the only update in the 7th edition is the inclusion of thePD-L1 inhibitor Atezolizumab (Atezolizumab) developed by Roche's Genentechcompany into the postoperative adjuvant treatment of NSCLC.This is the firsttime that ICI have been wrote into the guideline.

01

NSCLC 2021 Version 7

▲The update information of version 7 compared to version 6

Specifically, the guidelines clarify the conditionsfor the use of atelizumab, that is, "completely resected stage IIB-IIIA orhigh-risk stage IIA patients with tumor cell PD-L1 expression ≥1%, andpreviously received adjuvant chemotherapy for NSCLC patients”. At the sametime, it is recommended to "detect the PD-L1 status of surgical tissue orbiopsy specimens from patients with stage II-IIIA"

▲Treatment methods

02

Clinical trials and approvalof Atelizumab

The update of the NCCN guidelines comes from a newapproval that FDA approved atelizumab (trade name TECENTRIQ) for use in stageII to stage IIIA adults with tumor cell PD-L1 expression ≥1% Single-agentadjuvant therapy for NSCLC patients after surgery and platinum chemotherapy.This approval is based on the results of IMpower010 (NCT02486718), which is arandomized, multicenter, open-label Phase 3 clinical study to evaluate completeresection of IB-IIIA stage NSCLC patients after platinum chemotherapy. Theefficacy and safety of Rizumab versus the best supportive treatment werepublished in the journal Lancet.

Eligible patients are 18 years or older, completelyresected stage IB (tumor> 4 cm) to stage IIIA NSCLC patients (according tothe American Joint Committee on Cancer (AJCC) staging system (7th revision)).After 1 to 4 cycles of adjuvant platinum-based chemotherapy, patients wererandomly assigned (1:1) to receive adjuvant atelizumab (1200 mg every 21 days,continuous use for 16 cycles or 1 year) or optimal Support treatment(observation and regular scans for disease recurrence). The primary studyendpoint is the disease-free survival rate (DFS) assessed by the investigator.

▲Impower010 Research plan

Between October 7, 2015 and September 19, 2018, 1280patients were enrolled after complete resection, 1269 patients receivedadjuvant chemotherapy, of which 1005 patients were randomly assigned to theatilizumab group ( n=507) or the best support group (n=498), 495 patients ineach group received treatment. After a median follow-up time of 32.2 months(IQR 27.4-38.3), compared with the best supportive treatment, atelizumabtreatment increased tumor cell PD-L1 expression by ≥1% in stage II to stageIIIA patients DFS (NE VS 35.3 months, HR=0.66; 95% CI 0.5-0.88, p=0.0039). TheHR of DFS for all patients in stage II-IIIA was 0.79 (95% CI 0.64-0.96,p=0.02). The HR of the intention-to-treat (ITT) population (IB-IIIA) was 0.81(0.67-0.99; p=0.04). OS data is not yet come out.

▲DFS in tumor patients with PD-L1 expression ≥1%

In the safety, all observable adverse events (AEs) inthe atilizumab group were higher than those in the best support group (92.7% VS70.7%). Grade 3/4 AEs were 22% VS 12%. Grade 5 is 2% VS 1%, and serious adverseevents are 18% VS 8%. Compared with the best supportive treatment group,atelizumab has a higher toxicity, which requires a comprehensive evaluation inconjunction with its benefits.

03

VENTANA PD-L1 (SP263) Assay

In June 2021, based on the Impower010 clinical trial,the FDA approved the VENTANA PD-L1 (SP263) Assay as a companion diagnosis ofatilizumab for the selection of NSCLC patients with tumor cell PD-L1 expression≥1%. However, due to the high sensitivity of SP263 in tumor cells, the studyfinally adopted SP263 as the criterion.

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Other Clinical Research

In addition to atelizumab, there are also clinicalstudies on adjuvant/new adjuvant therapy for a number of ICIs, such as earlystage NSCLC patients who receive or do not receive adjuvant chemotherapy aftersurgical resection, use pembrolizumab Phase III clinical study (KEYNOTE-091) ofadjuvant therapy with monoclonal antibodies versus placebo. These researchresults will make more treatment choices for clinicians.

Reference

[1] NCCN 2021 V7

[2] Lancet. 2021 Oct9;398(10308):1344-1357.

[3] FDA Official website data

[4] ClinicalTrials database