At present, it is recommended to continue immunotherapy until progression or unacceptable toxicity.

However, only a minority of patients benefits from a durable response and most see the disease progress despite several months of control under immunotherapy. Multimodal approaches have been developed to improve their prognosis.

This study, randomized, open-label study aims to evaluate the impact of addition of ablative radiotherapy on OS of patients with NSCLC and oligometastatic lesions and treated by immunotherapy in first line (potentially associated with chemotherapy) or beyond. Stereotactic radiotherapy will be performed on a maximum of 5 residual hypermetabolic lesions seen on 18F-FDG PET / CT, in patients responding to immunotherapy (or with a stable disease) for at least 6 months.

Description of the modalities for recruiting :

During a standard consultation, the oncologist presents the study to the patient with locally advanced or metastatic non-small cell lung cancer long-term responders to immunotherapy. He gives the patient the consent form to participate in the study.

Once the consent form has been signed by the patient and the investigator, the investigator prescribes a screening test which must be carried out within 30 days before the randomization (Day 0, D0).

The screening step includes in particular a complete physical exam, a clinical laboratory tests a thoraco abdomino pelvic (TAP) and cerebral CT scan, a cerebral MRI (for patients with cerebral lesions observed on cerebral CT scan), a Spinal MRI (for patients with bones lesions observed on TAP CT scan), a PET scan (18F-FDG) (the results will be routinely interpreted in the centre and will be centrally reviewed), Patient Reported Outcome (PRO), QLQ-C30 and QLQ LC13

The inclusion of a patient is conditioned by the following definitive criterion : Maximum 5 residual hypermetabolic lesions measured on the CT from the 18F-FDG PET / CT centrally reviewed, including primary tumor and a maximum of 3 brain asymptomatic metastases (even if they are poorly seen in 18F- FDG PET/CT) treatable in stereotactic radiotherapy.

Patients registration and randomization :

Any patient who has signed an informed consent form (ICF) must be registered in the eCRF in order to be assigned a patient number.

Randomization will be centralized and performed via the eCRF. Patients will be randomly assigned (1:1) to either continuation of immunotherapy alone or addition of local ablative radiotherapy to immunotherapy.

The randomization procedure using minimization method will be stratified by the investigation center, by the treatment line (1 vs ≥2) and by the immunotherapy (pembrolizumab and nivolumab versus atezolizumab).

Treatment period :

Both arms continue the anti-PD1 or anti-PDL-1 immunotherapy according to the medical prescription.

Arm A (experimental), SRT start maximum 3 weeks after randomisation

Follow-up visits include in particular a complete physical exam, a clinical laboratory tests, a thoraco abdomino pelvic and cerebral CT scan, a cerebral MRI (for patients with cerebral lesions observed on cerebral CT scan), a Spinal MRI (for patients with bones lesions observed on TAP CT scan), a PET scan (18F-FDG) at 6 months post-randomization only (the results will be routinely interpreted in the centre and will be centrally reviewed) ; Patient Reported Outcome (PRO), QLQ-C30 and QLQ LC13

Imaging surveillance (CT scan +/- cerebral MRI +/- spinal MRI) will be performed for each patient up to progression or up to 12 months after randomization of the last patient included in the absence of progression.

Vital status is collected once a year and also date of death if applicable for each patient up to 12 months after randomization of the last patient included.

Inclusion Criteria:

• Patient aged 18 or more,
• Patient treated for histologically proven non-small cell lung cancer,
• Stage IIIB or IV,
• Performance status 0 to 2,
• Patient treated by immunotherapy (anti PD-1 or anti PD-L1) started for at least 6 months and regardless of the treatment line (in first line, immunotherapy may have been combined with chemotherapy),
• Response or stable disease on thoraco abdomino pelvic and cerebral CT scan,
• Maximum 5 residual hypermetabolic lesions measured on the 18F-FDG PET / CT centrally reviewed, including primary tumor and a maximum of 3 asymptomatic brain metastases (even if they are poorly seen in 18F- FDG PET/CT) treatable in stereotactic radiotherapy (extracerebral lesions ≤ 4cm and brain lesions ≤ 3cm measured on CT scanners)
• Effective contraception used in women of childbearing potential
• Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations,
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up,
• Patient has valid health insurance.

Exclusion Criteria:

• Persistence of grade 2 or greater adverse effects of immunotherapy,
• Infection in progress,
• At least one of the 5 hypermetabolic lesions measured on the 18F-FDG PET / CT centrally reviewed in a previously irradiated area,
• Uncontrolled severe comorbidity,
• History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥ 3 years and of low potential risk for recurrence ; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease ; Adequately treated carcinoma in situ without evidence of disease
• Pregnant or nursing patient
• Patient deprived of liberty or under guardianship,
• Patient unable to undergo regular medical check-ups for geographical, social or psychological reasons.
• Disorder precluding understanding of trial information or informed consent