Re-induction of a Systemic Immune Response in Metastatic or Locally Recurrent Lung Cancer

Patients with metastatic non-small cell lung cancer (NSCLC) who after an initial response to immunotherapy of chemo-immunotherapy show diffuse disease progression are treated with chemotherapy, with a median PFS of about 3 months and a high incidence of important toxicity or by continuation of immune therapy when the growth rate of the tumours is low. In a previous study, it was showed that irradiating a single metastatic lesion and continuation of immune therapy resulted in a median PFS time was 4.9 months (95% CI, 3.0-7.0 months). At three months of follow-up, the PFS rate was 62.5%, at six months 37.5% and at 12 months 17.9%. The median OS for all patients was 14.9 months (95% CI, 12.2-21.5 months). Toxicity was hardly observed. This was obtained with a few fractions of radiotherapy. There is biological rationale to deliver this radiation in a single fraction of 10 Gy. Objective: The primary objective is to investigate if a single fraction of 10 Gy is not inferior to a more fractionated schedule, which would add to the convenience for the patient, even less toxicity and costs. Study design: Prospective, single-arm phase II trial. Study population: Patients with stage IV NSCLC who initially showed a partial or complete remission under immune therapy alone or concurrent immune therapy and chemotherapy and now show progressive disease according to RECIST 1.1 criteria. At least two different lesions should show progressive disease. Patients should be able to continue the same immune therapy (i.e. no adverse events grade 3 or more). Intervention: Patients continue the same immune therapy they already received and get radiotherapy to one progressing lesion. The lesion may or may not be symptomatic. The preferred radiotherapy dose is 10 Gy in 1 fraction, but other fractionation schedules (e.g. 24 Gy/ 3 fractions, 30 Gy/ 10 fractions, 20 Gy/ 5 fractions, 20-24 Gy / 1 fraction for stereotactic radiotherapy for brain metastases), including so-called isotoxic strategies are allowed if these are standard for a certain location or palliative indication in the body. Main study parameters/endpoints: Progression-free survival (PFS).

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Stage IV NSCLC
* An initial partial or complete remission under immune therapy alone or concurrent immune therapy and chemotherapy
* Subsequently progressive disease according to RECIST 1.1 criteria
* Considered by the treating physician to be able to continue the same immune treatment as standard of care
* At least two different lesions should show progressive disease
* At least one progressing lesion should be eligible for radiation

Exclusion Criteria:

* Patients with any grade 3 or higher toxicity from previous therapy
* Patients who are not eligible for continuation of the immune therapy according to standard practice
* Corticosteroids in a dose above 10 mg prednisone or equivalent per day. Corticoids used as supportive therapy for systemic or radiotherapy are allowed