Immunotherapy for the Treatment of Lung Cancer and Mesothelioma

Publication Date: May 31, 2022
Last Updated: June 7, 2022

Molecular Testing

  • Comprehensive next-generation sequencing (NGS) testing of tumor tissue is recommended for all patients with metastatic non-squamous NSCLC and select patients with squamous carcinoma of the lung (eg, never-smokers) if feasible (LE: 2).
  • When NGS is not possible, tumor tissue should be tested for EGFR, ALK, ROS1, BRAF, MET ex14, RET, NTRK, and KRAS G12C alterations for all patients with non-squamous NSCLC and selected patients with squamous cell.
  • Tumor tissue should be tested for molecular driver oncogenes for patients with metastatic NSCLC adenocarcinoma with any smoking history, and for patients with light or never smoking history with non-adenocarcinoma histology (LE: 3).
  • ICIs should not be initiated until the results of molecular driver mutation testing are available, regardless of tumor PD-L1 expression status.
  • Testing for tumor PD-L1 expression should be performed for patients with metastatic (stage IV) NSCLC of any histology to predict the likelihood of clinical benefit from anti-PD-(L)1 ICI therapy (LE: 2).
  • Testing for tumor PD-L1 expression can be considered, but is not required, for patients with stage III unresectable NSCLC to predict the likelihood of clinical benefit from anti-PD(L)1 ICI therapy.
  • For resectable stage II to IIIA NSCLC, testing for tumor PD-L1 expression should be performed to be considered for atezolizumab therapy in the adjuvant setting following resection and platinum-based chemotherapy (LE:2).
  • For PD-L1 assessment, the 22C3, 28–8, and SP263 assays are interchangeable. The SP142 assay is not interchangeable and does not perform equivalently to the other assays listed (LE: 3).
  • Archived or fresh biopsy material can be used for PD-L1 assessment (LE: 3). Previously cut slides that are less than 3 months old can be used for PD-L1 assessment.
  • Testing for PD-L1 expression in SCLC or mesothelioma is not known to be predictive of benefit with immunotherapy at this time.
  • TMB and MSI are the basis for tumor-agnostic indications for ICI therapy and have demonstrated clinical utility in many tumor types, but in lung cancer there are insufficient data to recommend routine testing for these biomarkers (LE: 2).

Resectable stage II to IIIA NSCLC

  • For patients with metastatic NSCLC with no actionable mutations and TPS ≥50%, the panel recommends first-line pembrolizumab, atezolizumab, or cemiplimab monotherapy, with consideration for chemo-immunotherapy for patients with high tumor disease burden or worrisome symptoms (LE:2).
  • For patients with metastatic NSCLC with no actionable mutations and TPS <50%, pembrolizumab with chemotherapy, atezolizumab with chemotherapy (with or without bevacizumab), or nivolumab with ipilimumab with or without 2 cycles of chemotherapy (in select cases) should be used (LE:2).
  • For patients with metastatic NSCLC with no actionable mutations and tumor PD-L1 expression 1%–49% who are ineligible for or refuse chemotherapy, pembrolizumab monotherapy may be considered (LE:2).
  • For patients with metastatic NSCLC with tumor PD-L1 expression ≤1% and baseline brain metastases or squamous histology nivolumab in combination with ipilimumab may be considered (LE:3).
  • For adult patients with resectable (tumors ≥4 cm or node positive) NSCLC, nivolumab in combination with platinum-doublet chemotherapy every 3 weeks for 3 cycles in the neoadjuvant setting may be considered (LE:2).
  • For adult patients with stage II to IIIA NSCLC and PD-L1 expression ≥50%, atezolizumab is recommended as an adjuvant treatment following resection and platinum-based chemotherapy (LE:2).
  • For adult patients with stage II to IIIA NSCLC and PD-L1 expression 1%–49%, atezolizumab may be considered as an adjuvant treatment following resection and platinum-based chemotherapy (LE:2).
  • In patients with non-squamous cell NSCLC tumors positive for EGFR, ALK, or ROS1 alterations, appropriate FDA-approved targeted therapy should be administered as first-line therapy (LE:1).
  • In patients with non-squamous cell NSCLC tumors positive for EGFR, ALK, or ROS1 alterations that become refractory to TKIs, chemotherapy should be given, with consideration for the addition of immunotherapy (LE:2) and antiangiogenic therapy.
  • In patients with non-squamous cell NSCLC with tumors positive for actionable molecular alterations other than EGFR, ALK, or ROS1 alterations, appropriate FDA-approved targeted therapies can be considered as first-line therapy.
  • Whenever possible, patients should be offered participation in clinical trials.

Overview

Title

Immunotherapy for the Treatment of Lung Cancer and Mesothelioma

Authoring Organization