Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: Immunotherapy With or Without SBRT in Patients With Stage IV Non-small Cell Lung Cancer

Summary: This phase III trial studies immunotherapy and stereotactic body radiation therapy to see how well it works compared with immunotherapy alone after first-line systemic therapy (therapy that goes throughout the body) in treating patients with stage IV non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving immunotherapy with stereotactic body radiation therapy may work better than immunotherapy alone in treating patients with non-small cell lung cancer.

Detailed description: PRIMARY OBJECTIVES:
  I. To compare progression-free survival of patients randomized to radiation and consolidative immunotherapy against those receiving consolidative immunotherapy alone.
  SECONDARY OBJECTIVES:
  I. To estimate overall survival in all patients and will compare overall survival of those randomized to radiation and consolidative immunotherapy against those receiving consolidative immunotherapy alone.
  II. In patients receiving radiation, to describe the rate of in-field local control and rate of out-of-field disease progression with serial imaging.
  III. In patients not receiving radiation, describe progression at known sites of disease after first line systemic therapy and rate of development of new metastases with serial imaging.
  IV. To evaluate toxicity associated with radiation followed by consolidative immunotherapy.
  OUTLINE: Patients are randomized to 1 of 2 arms.
  ARM I: Patients undergo 3-10 treatments of stereotactic body radiation therapy (SBRT). Patients also receive pembrolizumab intravenously (IV) over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.
  ARM II: Patients receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.
  After completion of study treatment, patients are followed up at 1 month, every 3 months for 1 year, every 6 months for the next 2 years, and then annually for 2 years.

Eligibility: Inclusion Criteria:
  -  Patients with newly diagnosed, de novo American Joint Committee on Cancer (AJCC) eighth edition stage 4 metastatic non-small cell lung cancer (NSCLC)
  -  Pathologic diagnosis of non-small cell lung cancer prior to enrollment
  -  Patients can be registered on study prior to or during systemic chemotherapy. Only those with at least stable disease, no new sites of disease, and all known metastatic lesions amenable to local radiotherapy will be eligible for randomization
  -  Maximum number of sites per patient will be six total at time of enrollment, with the primary and or regional lymph nodes counting together as one site and any central nervous system (CNS) disease treated with stereotactic radiation counted as 1 site. A patient may have multiple brain lesions, but as long as they are treated with stereotactic radiosurgery (SRS) these will cumulatively be considered as one site. Brain lesions may be treated with SRS prior to randomization. Organ-specific limits apply as below
  -  There are no strict size or tumor number limitations in lung, liver, abdomen pelvis, or spine organ sites, however the treating radiation oncologist must agree that dosimetric constraints are likely to be respected if all known sites of disease remain stable following line systemic therapy
  Lung
  • Patients with two or more lung lesions determined by the treating clinician to be synchronous early-stage primary cancers will not be eligible
  Primary site:
  -  T1-2N0 primary lesions may also be treated with stereotactic body radiation therapy (SBRT)
  -  T1-4N1-3 disease may be treated with radiation therapy using 2 to 7 weeks of daily radiotherapy with or without concurrent chemoradiation at the discretion of the treating clinician, however they must be able to anticipate meeting applicable dosimetric guidelines
  -  Performance status 0-2 (Eastern Cooperative Oncology Group [ECOG]) at randomization
  -  A signed study specific consent form is required
  -  Leukocytes >= 3,000/mcL
  -  Absolute neutrophil count >= 1,500/mcL
  -  Platelets >= 100,000/mcL
  -  Total bilirubin within normal institutional limits
  -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  -  Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  Exclusion Criteria:
  -  Patients with a history of prior radiation to the sites involved
  -  Pregnant or lactating women
  -  Treatment for other carcinomas within the last three years? (Except for cured non-melanoma skin cancer, low-risk prostate cancer, T1/T2 glottic cancer, stage I breast cancer, non-invasive bladder cancer, or treated in-situ cervical cancer and breast cancer)

Relevance to patient case: not relevant