Ablative radiotherapy for oligoprogressive disease in non-small cell lung cancer treated with Pembrolizumab

Purpose: Oligoprogression (OP) in lung cancer is defined as the isolated progression of 1 to 5 existing lesions or the metachronous appearance of metastatic lesions. Stereotactic radiotherapy is a non-invasive technique whose effectiveness and safety have been studied in oligoprogressive cohorts receiving maintenance immunotherapy, but few studies have demonstrated its effects on morbidity and mortality. Objective: To investigate the benefit of radiotherapy in patients with metastatic non-small cell lung cancer (NSCLC) undergoing maintenance treatment with pembrolizumab who experience oligoprogression in terms of time to next treatment (TTNT), overall survival (OS), and progression-free survival (PFS) while continuing pembrolizumab following radiotherapy. Methods: Retrospective observational monocentric study in patients with NSCLC who received first-line chemotherapy and pembrolizumab or pembrolizumab alone, and who experienced oligoprogression during maintenance treatment, treated with radiotherapy between August 2019 and July 2022. Results: Thirty-six patients were included in the study. 72.2% were males with a median age at diagnosis of 67 years. Adenocarcinoma was represented in 69.4% of cases, while 30.6% of patients had squamous cell carcinoma. 55% patients of tumours had a PD-L1 score > 50%. The most common metastatic sites at diagnosis were pulmonary (38.4%), bone (25%), and lymph nodes (25%). 47 OP were treated, with 45 of them involving a single lesion, primarily located in the lung and brain. All were treated either with stereotactic radiotherapy (59.6%) or IMRT (40.4%). The TTNT in our cohort was 16.5 [12.4 - NA] months. In multivariate analysis, diabetes (HR 7.85 [2.06-30.0], p = 0.003) and adrenal gland metastasis at diagnosis was statistically correlated with a shorter TTNT (HR 6.30 [1.27-31.3], p=0,024). The OS in our cohort was 35.5 [27.9 - 46.4] months. In multivariate analysis, bone metastases (HR 8.52 [1.16 - 62.6], p=0.035) and adrenal metastases (HR 17.65 [1.56 - 200], p=0.02) are aggravating factors, as well as being more than 70 years old (HR 10.49 [1.37 - 80.3], p=0.024). PFS was 20.8 [12.6 - 37.3] months. OP involving the pleura (HR 5.36 [1.54 - 18.7], p=0.003) or bone (HR 3.05 [1.26 - 7.36], p = 0.009) was associated with earlier recurrence of another OP or overall progression. OP in the lung (HR 0.33 [0.1 - 1], p = 0.057) potentially improved PFS but approached significance. Conclusion: Radiotherapy followed by maintenance pembrolizumab treatment, in a subset of metastatic NSCLC patients selected for OP, delay the initiation of a second-line treatment and is associated with significant PFS abd OS. It is also very well tolerated. These findings remain to be confirmed in the context of randomized controlled trials. (author)