To determine whether in patients with EGFR mutated advanced NSCLC and osimertinib as first-line treatment, the (repeated) use of LAT to ≤ 3 OP lesions and continuation of first-line osimertinib, improves the median progression-free survival by more than 3 months (i.e. PFS2-PFS1 = >3 months).

The (repeated) use of LAT to ≤ 3 OP lesions with continuation of first-line osimertinib, is endorsed by international guidelines (NCCN, ESMO).

In this phase IIb prospective non-randomized observational trial, we want to document the benefit of LAT in this patient cohort.

Inclusion Criteria:

1. Male or female, ≥ 18 years of age
2. Established histological diagnosis of advanced NSCLC, not suitable for radical treatment, with an EGFR actionable mutation receiving first-line targeted TKI therapy with osimertinib
3. Initial radiologically confirmed response (at least stable disease) to osimertinib assessed 3 months post commencing osimertinib according to RECIST criteria v1.1.
4. Confirmed OPD defined as ≤ 3 intra- and extracranial sites of progressive disease. OP may be defined as progression of an individual metastasis according to RECIST or on 2 consecutive imaging studies at least 2 months apart with a minimum of 5mm increase in size from baseline or an unambiguous development of a new metastatic lesion with a grand total of 3 lesions. All sites must be visible, imaging defined targets, not previously treated with radiation or radiofrequency and suitable for treatment with LAT as determined by the local multi-disciplinary team (MDT).
5. Adequate baseline organ function to allow LAT to all the OP targets.
6. Predicted life expectancy ≥ 6 months
7. Karnofsky Index ≥ 60% and ECOG 0-2
8. Provision of written informed consent
9. Female participants must be surgically sterile or postmenopausal if SBRT is planned to the abdominal area or must agree to use effective contraception during the period of therapy.

Exclusion Criteria:

1. > 3 sites of progressive disease
2. Oligoprogressive metastases not amenable to LAT
3. Radiotherapy or radiofrequency ablation near the OP lesion prior to the inclusion in the LAT-FLOSI study
4. Co-morbidities considered clinically precluding the safe use of LAT
5. Any psychological, sociological or geographical issue potentially hampering compliance with the study
6. Pregnancy

Established histological diagnosis of advanced NSCLC, not suitable for radical treatment, with an EGFR actionable mutation receiving first-line targeted TKI therapy with osimertinib. Confirmed oligoprogressive disease defined as ≤ 3 intra- and extracranial sites of progressive disease