Last updated June 7, 2022

Immunotherapy for the Treatment of Lung Cancer and Mesothelioma

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.

Treatment of relapsed/refractory SCLC

  • Patients with ES-SCLC and no contraindication for the use of ICIs should be treated with first-line carboplatin, etoposide, and atezolizumab or platinum-based chemotherapy, etoposide, and durvalumab, both during induction chemotherapy and as maintenance (LE:2).
  • For patients with ES-SCLC following the completion of induction chemotherapy plus ICI, PCI is not currently recommended outside of a clinical trial setting.
  • The use of thoracic radiation following completion of induction chemotherapy plus ICI in patients with ES-SCLC is not recommended outside of a clinical trial setting.
  • Whenever possible, patients should be offered participation in clinical trials.

Mesothelioma

  • For the diagnosis of mesothelioma, an adequate tissue biopsy should be used. The pathology report for mesothelioma should preferably include the histologic subtype, specifically epithelioid, biphasic, or sarcomatoid.
  • Germline genetic testing for BAP1 mutation should be considered for patients with mesothelioma especially those with a family history of mesothelioma or other BAP1 associated cancers such as uveal melanoma, cutaneous melanoma, kidney or bladder cancer, or age less than 60 years (LE:4).
  • In newly diagnosed patients with mesothelioma, a multidisciplinary approach that includes consultation with thoracic surgeons, pulmonologists, radiation oncologists, and medical oncologists should be considered to determine if they are candidates for maximum cytoreductive operation such pleurectomy and decortication or extrapleural pneumonectomy with or without radiation therapy.
  • Whenever possible, patients should be offered participation in clinical trials.
  • For patients with epithelioid subtype mesothelioma, treatment with nivolumab plus ipilimumab may be considered based on comparable outcomes to SOC chemotherapy. However, treatment decisions should be individualized and take into account the differing side effect profiles of combination immunotherapy and chemotherapy (LE:2).
  • For patients with non-epithelioid subtype mesothelioma, treatment with nivolumab plus ipilimumab is strongly recommended based on an almost twofold increase in median OS compared with SOC chemotherapy (LE:2).
  • For patients with mesothelioma, routine PD-L1 testing is not recommended, as benefit from immunotherapy with nivolumab plus ipilimumab was seen regardless of PD-L1 expression (LE:2).
  • Routine TMB testing is not recommended for patients with mesothelioma.
  • For patients with mesothelioma that has progressed following front-line treatment with nivolumab and ipilimumab, platinum-based chemotherapy with pemetrexed should be considered (LE:2).
  • Patients with mesothelioma that have progressed following immunotherapy and pemetrexed with platinum-based chemotherapy should be encouraged to enroll in clinical trials.

Radiographic response to immunotherapy

  • For patients commencing ICI-based therapy for lung cancer, a baseline CT should be performed within 4 weeks before the first dose of therapy.
  • The first follow-up CT imaging on therapy should be performed 6–9 weeks (approximately 2–3 treatment cycles) after the commencement of ICI-based therapy, and the timing should be adapted to the dosing schedule of the systemic therapy.
  • If a patient is clinically stable or improved, it is reasonable to continue therapy beyond radiographic progression. Repeat CT imaging should be performed within 4–8 weeks to rule out continued disease progression and monitor for toxicities.
  • For a patient who has been treated with immunotherapy beyond radiographic progression and has continued disease progression at the time of follow-up imaging and/or clinical deterioration, strong consideration should be given to looking for an alternative systemic therapy.

Understudied patient populations

  • For patients with advanced lung cancers and active autoimmune conditions or SOTs, the use of immunotherapy merits a thoughtful multidisciplinary approach requiring a discussion with the treating team, including subspecialists and the oncologist, and the patient regarding the risk of autoimmune activation against the potential for benefit with ICI treatment. Given the lack of prospective clinical trial data, whenever possible patients in these groups should be encouraged to enroll in clinical trials.
  • Baseline interstitial lung disease and/or a high risk for pneumonitis are relative contraindications to ICI therapy (LE:3).
  • For patients with pre-existing autoimmune disorders that are controlled with chronic low dose immunosuppression, ICI therapy is not necessarily absolutely contraindicated. However, immunotherapy should be avoided in patients with poor control of autoimmune disease (requiring high doses of immunosuppressants) and in patients with life-threatening and/or CNS autoimmune disease (LE:3).
  • For patients with SOTs, the impact of graft rejection should be weighed against the potential benefit of ICI treatment. In most cases, the ramifications of graft rejection will outweigh the palliative benefits of ICI treatment, although renal transplant patients may represent an exception (LE:1).

Recognition and management of irAEs

  • For patients with lung cancer receiving ICI therapy who develop symptoms of irAEs, management should follow established guidelines. The management of ICI-related toxicity in patients with lung cancer is identical to management in other malignancies.

Patient support and QOL

  • All patients receiving treatment with ICIs should receive detailed education about the potential immune-related toxicities associated with therapy.
  • Support tools should be provided to guide patients and caregivers in self-monitoring to support appropriate intervention.
  • It is important to discuss the financial impact of immunotherapy treatment with patients and their care-partners, and to assist in identifying resources for them to find support.

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Recommendation Grading

Overview

Title

Immunotherapy for the Treatment of Lung Cancer and Mesothelioma

Authoring Organization

Publication Month/Year

May 31, 2022

Document Type

Guideline

Country of Publication

US

Document Objectives

Immunotherapy has transformed lung cancer care in recent years. In addition to providing durable responses and prolonged survival outcomes for a subset of patients with heavily pretreated non-small cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs)- either as monotherapy or in combination with other ICIs or chemotherapy-have demonstrated benefits in first-line therapy for advanced disease, the neoadjuvant and adjuvant settings, as well as in additional thoracic malignancies such as small-cell lung cancer (SCLC) and mesothelioma. Challenging questions remain, however, on topics including therapy selection, appropriate biomarker-based identification of patients who may derive benefit, the use of immunotherapy in special populations such as people with autoimmune disorders, and toxicity management. Patient and caregiver education and support for quality of life (QOL) is also important to attain maximal benefit with immunotherapy. 

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Assessment and screening, Treatment, Management

Diseases/Conditions (MeSH)

D007167 - Immunotherapy, D008175 - Lung Neoplasms, D008654 - Mesothelioma, D000086002 - Mesothelioma, Malignant

Keywords

immunotherapy, lung cancer, mesothelioma, Cancer immunotherapy

Source Citation

Govindan R, Aggarwal C, Antonia SJ, Davies M, Dubinett SM, Ferris A, Forde PM, Garon EB, Goldberg SB, Hassan R, Hellmann MD, Hirsch FR, Johnson ML, Malik S, Morgensztern D, Neal JW, Patel JD, Rimm DL, Sagorsky S, Schwartz LH, Sepesi B, Herbst RS. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma. J Immunother Cancer. 2022 May;10(5):e003956. doi: 10.1136/jitc-2021-003956. PMID: 35640927.v