Radiotherapy in patients with NSCLC developing progressive disease during immune checkpoint inhibition: Abscopal responses and survival

Objective: Increasing evidence suggests that RT and ICI have synergistic effects on anti-tumor immune response, and abscopal responses (AR) have been described more frequently with this combination. Here, we analyzed the frequency and factors associated with AR in NSCLC patients receiving ICI and RT. Methods: In ARTIC (ARO 2022-10, DRKS00032390), a multicenter, retrospective study, patients treated with RT for progressive disease during or after receiving ICI were analyzed for abscopal benefit (AB) and overall survival (OS). Patients were grouped by non-irradiated lesion response; logistic and Cox regression were used to analyze factors linked to AR, AB, and OS. Results: Fifty-six patients from 13 centers with 137 non-irradiated lesions were analyzed. Most received hypofractionated or stereotactic RT. The most common RT sites were lung, bone, and brain. Thirty-three patients showed AB, with 15 patients developing an AR in at least one non-irradiated lesion. In the logistic regression analysis, older age was associated with a higher rate of AP (odds ratio (OR): 1.07, 95%-CI: 1.00-1.14; p = 0.05). Male sex showed a trend towards higher risk of AP (OR = 3.13; 95%- CI: 0.93-11.86; p = 0.075). In the multivariable Cox analysis, ECOG performance score at the start of RT (hazard ratio (HR): 0.29, 95%-CI: 0.12-0.69; p < 0.01) and oligometastatic disease (HR: 0.34, 95%-CI: 0.12-0.94; p = 0.039) were significantly associated with improved OS. Conclusion: RT was able to induce AR in some NSCLC patients who were progressive under ICI, possibly delaying a switch in systemic treatment. AB was less frequent in older patients and in men.