Introduction: Long-term analysis of PACIFIC revealed the clinical benefit of chemoradiotherapy combined with Durvalumab for unresectable non-small-cell lung cancer (NSCLC) stage III. ALLSTAR is a prospective registry aimed at validating the PACIFIC regimen in daily practice in Austria. Patients and Methods: Patients were eligible if they had pathologically confirmed unresectable NSCLC III with a curative treatment option. The endpoints for this analysis were overall survival (OS), updated local control (LC), and progression-free survival (PFS). Results: The 2- and 3-year LC rates in patients who received total radiation doses > 66 Gy were 80% and 75%, respectively, which were superior to the standard treatment (65% and 54%; p-value 0.085). This benefit was even more pronounced in Durvalumab patients with 2- and 3-year LC rates of 82% and 79% with >66 Gy (p-value 0.068). The 2- and 3-year OS with Durvalumab was 71% and 63%, respectively, compared to 58% and 44% without Durvalumab (HR 0.552; 95%-CI 0.347–0.881; p-value 0.011). Patients who were treated with Durvalumab also had a significantly longer 2- and 3-year PFS (56% and 48%) than those without (35% and 20%; HR 0.469; 95%-CI 0.312–0.707; p-value < 0.001). Pulmonary side effects were observed in 66/188 (35%) patients, with one case of grades 4 and 5 each. Oesophageal toxicity grade 1–3 occurred in 93/188 (49%) cases. Conclusion: The updated ALLSTAR analysis demonstrated sustained benefit of Durvalumab for OS and PFS, as well as a possible long-term benefit of radiation dose escalation > 66 Gy on LC.

Background/Objectives: Current evidence suggests that patients with unresectable non-small cell lung cancer (NSCLC) whose tumours harbour driver mutations do not benefit from immune checkpoint inhibition. Kirsten rat sarcoma virus mutations (KRASmts), however, seem to be the exceptions to the rule. To this end, we compared KRASmt patients who were treated with immunotherapy to those without. Methods: ALLSTAR is a nationwide registry for patients with histologically verified non-operable NSCLC aged 18 or older having a curative treatment option. This report presents a subcohort of KRASmt patients who were recruited between 2020/03 and 2023/04. The diagnostic work-up included ¹⁸F-FDG-PET-CT scan and contrast-enhanced cranial CT or—preferably—MRI. Patients were treated with chemoradiotherapy (CRT) either followed by immune checkpoint inhibition (ICI) or not. Results: Thirty-two KRASmt patients with a median follow-up of 25.9 months were included in this analysis. After CRT, 27/32 (84%) patients received ICI. The 2-year overall survival rate in KRASmt patients who received immunotherapy was significantly better compared to those without ICI (N = 32; 84% versus 20%; p < 0.001). Likewise, the 2-year progression-free-survival with immunotherapy was also significantly better than in those without ICI (N = 32; 75% versus 20%; p < 0.001). Of the 12/32 patients (38%) who had received radiation doses > 66 Gy, none had a locoregional relapse, whereas in the other 20 patients, 5 (25%) events occurred (p-value = 0.116). Conclusions: Since KRASmt patients could benefit from ICI treatment, immunotherapy should be offered to these patients, similar to those without actionable genetic drivers. Additionally, radiation dose escalation > 66 Gy may also improve locoregional control in this subset of patients.

Introduction: The incidence of NSCLC increases with age, with a median of approximately 70 years at diagnosis. Historically, treatment strategies for locally advanced cancers have been developed predominantly in younger populations, often excluding elderly patients who may present with multiple comorbidities, severely impaired lung function, or decreased performance status, leading to a lack of age-relevant clinical data. Therefore, we performed a subanalysis of real-world data from the ALLSTAR study to investigate the impact of durvalumab and the radiation regimen (sequential versus concurrent) on clinical outcome in elderly patients with unresectable stage III NSCLC. Methods: We included a total of 171 patients in this subanalysis. All patients were diagnosed with unresectable stage III NSCLC. Patients were divided into two age groups, ≥70 (41%) and <70 years (59%). All of them received curative chemoradiotherapy with (66%) or without (34%) durvalumab. Results: Patients were followed up for a median time of 25.1 months (range: 3.3–52.1). In the elderly group, patients who did not receive durvalumab consolidation had a median PFS of 17 months (95%-CI: 12.4—not reached) and a higher risk of progression (HR = 2.2; 95%-CI: 1–4.6) than those treated with durvalumab, which had a median PFS of 37 months (95%-CI: 24.5—not reached). This difference was statistically significant (log rank p = 0.026). Moreover, the Cox model yielded a hazard ratio suggesting a higher risk of locoregional (HR = 3.8; 95%-CI: 1.28–11.48; log rank p-value =0.01) as well as local recurrence (HR = 5.5: 95%-CI: 1.67–18.1: p-value =0.002) in patients who received sequential chemoradiotherapy compared to those with concomitant chemoradiotherapy in the same age group. In an exploratory analysis based on a Mann–Whitney U test, we did not find significant difference in toxicity between the two age groups. Conclusions: Durvalumab was associated with prolonged progression-free survival, while concomitant radiotherapy showed a trend towards improvement in locoregional and local control in patients aged ≥70. There was no significant difference in treatment toxicity found in the exploratory Mann–Whitney U analysis between the two age groups.

Background: As demonstrated by the PACIFIC trial, biomarker-driven patient selection is crucial. While treatment based on programmed death ligand-1 (PD-L1) and mutational status have become routine, tests for biomarkers available from pretherapeutic blood samples are currently a topic of scientific interest. Methods: This analysis was conducted on patients from the ALLSTAR RWD study, which is a nationwide, prospective registry for inoperable non-small cell lung cancer (NSCLC) stage III. Patients were amenable if they had a full routine pre-treatment blood sample, from which the following biomarkers were extracted: neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), derived monocyte-to-lymphocyte ratio (dMLR) and lactate dehydrogenase (LDH) levels. The intention was to find a cutoff for each of these biomarkers to predict locoregional control (LRC), progression-free survival (PFS) and overall survival (OS). Results: MLR and dMLR demonstrated their predictive potential with cutoff values of 0.665 and 0.945, respectively. Stratifying the whole cohort by means of these cutoffs demonstrated significantly better locoregional control for patients below the threshold, both in the whole cohort (N = 175; 55.7% vs. 75.5%; p-value = 0.018) and in the Durvalumab subgroup (N = 106; 57.5% vs. 77.3%; p-value = 0.030). Similar findings were observed for PFS in the whole cohort (N = 175; 20.5% vs. 56.1%; p-value p < 0.001) and in the Durvalumab subgroup (N = 106; 31.2% vs. 64.6%, p-value < 0.001). dMLR could also significantly predict PFS (N = 173; 17.4% vs. 56.3%; p-value < 0.001), which was corroborated in the Durvalumab subgroup (N = 108; 23.1% vs. 64.1%; p-value = 0.003). Conclusions: This explorative analysis demonstrates the predictive potential of MLR and dMLR for LRC and PFS. These blood biomarkers can be readily integrated into clinical routines since they are easily available.

Purpose: Chemoradioimmunotherapy (CRIT) with 60–66 Gy is the standard of care (SoC) for non-small-cell lung cancer (NSCLC) UICC stage III. The aim of this real-world data (RWD) study was to report the long-term impact of Durvalumab and radiation dose escalation on clinical outcomes. Material and Methods: ALLSTAR is a nationwide prospective multicentre registry for NSCLC UICC stage III, in which 12/14 Austrian centres participated (ethics approval number: 1002/2019). The basis for the current analysis is the third data extraction, which was completed on 2 June 2025. Apart from the SoC, alternative dose-fractionation and sequential CRT concepts >66 Gy were also permitted. Durvalumab maintenance treatment for one year was administered at the discretion of the tumour board at each centre. Results: Compared to prior analyses by our group, 40 individuals who completed follow-up (FUP) were added to this final analysis, leading to a total patient population of 228 (156 CRT plus Durvalumab; 72 CRT). In 156 patients, Durvalumab was added to CRT, while 72 received CRT only. The median FUP periods were 41.0 (95%-CI: 36.7–45.4) and 37.8 months (95%-CI: 31.4–44.1) for the Durvalumab and CRT cohort, respectively. Radiation dose escalation combined with Durvalumab treatment was associated with a nominally higher ITC of 37 months (95%-CI: 24.5-not reached) compared with 17.7 months (95%-CI: 14.9-not reached) in patients receiving neither dose escalation nor Durvalumab (N = 135; HR = 0.61; 95%-CI: 0.37–1.006; p-value 0.051). With Durvalumab maintenance, a median PFS of 22.8 months (95%-CI: 19.4–38.3) was observed compared to 16.5 months (95%-CI: 12.6–24.5) without (N = 228; HR = 0.61; 95%-CI: 0.42–0.88; p-value 0.0071). Median OS was 52.6 months (95%-CI: 39.5-not reached) with Durvalumab compared to 27.4 months (95%-CI: 18.7-not reached) without (N = 228; HR = 0.52; 95%-CI: 0.34–0.78; log-rank p-value < 0.002). Median time to death or distant metastasis (TTDM) was 33.3 months (95%-CI: 23.5–45) in the Durvalumab cohort compared to 18.7 months (95%-CI: 14.8-not reached) in the CRT cohort (N = 228; HR = 0.60; 95%-CI: 0.42–0.89; log-rank p-value 0.01). Median time to death or local relapse (TDLR) with Durvalumab was 30.4 months (95%-CI: 23.5–51.1) compared to 17.2 months (95%-CI: 14.8–25.7) without (N = 226; HR = 0.58; 95%-CI: 0.40–0.83; log-rank p-value < 0.003). Conclusion: This final RWD analysis implies both a beneficial effect of high-dose irradiation combined with Durvalumab on ITC and the long-lasting impact of Durvalumab on PFS, OS, TTDM, and TDLR.