Prognostic and predictive value of PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in locally advanced NSCLC treated with simultaneous radiochemotherapy in the randomized, multicenter, phase III German Intergroup lung Trial (GILT)

Tufman, Amanda; Neumann, Jens; Manapov, Farkhad; Sellmer, Laura; Jung, Andreas; Kauffmann-Guerrero, Diego; Kahnert, Kathrin; Mertsch, Pontus; Borgmeier, Astrid; Semrau, Sabine; Rittmeyer, Achim; Ulm, Bernhard; Ulm, Kurt; Flentje, Michael; Fietkau, Rainer; Huber, Rudolf M.

doi:10.1016/j.lungcan.2021.07.008

Cited by 12 publications

(16 citation statements)

References 18 publications

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“…These results are also in concordance with the distribution of PD-L1 expression values <1% from 30-35% and PD-L1 values ≥1% from 65-70% found in the literature as well as in a German prospective cohort, CRISP (15)(16)(17)(18). This results in a high level of consistency in PD-L1 expression in the patient groups examined, which also speaks for the stability of the detection method for PD-L1 expression (11)(12)(13). The methodology to evaluate PD-L1 expression was identical to the one used in the PACIFIC study.…”

Section: Similarities Of the Populationsmentioning

confidence: 93%

“…In contrast to these results, the study from T. Tokito et al with 74 patients in stage III NSCLC showed that PD-L1 expression was not correlated with PFS and OS (12). This has been con rmed by the study of A. Tufman et al In their study 78 patients with stage III NSCLC were included and PD-L1 expression did not correlate with PFS following RTCT (13). Our cohort with 99 patients is largest cohort ever analyzed regarding the prognostic impact of PD-L1 expression after radiochemotherapy.…”

Section: Introductionmentioning

confidence: 88%

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Evaluation of the prognostic impact of SP263-evaluated PD-L1 expression in patients with non-small cell lung cancer (NSCLC) stage III treated with radio-chemotherapy

Wagner¹,

Roeper²,

Heukamp³

et al. 2022

Preprint

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Background The PACIFIC study showed that patients with NSCLC after radio-chemotherapy derived a benefit in PFS and OS when treated with durvalumab, a PD-L1-inhibitor, vs placebo. In a post-hoc analysis this effect was limited to patients with a PD-L1 expression of > 1%, while patients < 1% did not benefit from durvalumab, partly because the outcome in the observational control arm was surprisingly favorable. Thus, it could be speculated that lack of PD-L1 expression confers a favorable outcome in stage III NSCLC. Intention We retrospectively analyzed PFS and OS in a group of 99 patients with stage III NSCLC homogeneously treated and not progressing after radio-chemotherapy. In all patients, PD-L1 expression was evaluated and outcome in the groups of PD-L1 < 1% and PD-L1 ≥ 1% was compared. Methods Clinical data, PD-L1 expression, predictive blood-markers and outcome were retrospectively captured from primary cases of the certified lung cancer center Oldenburg. Statistical analyses using log-rank test were performed. Results The median OS of the patients with an expression of PD-L1 < 1% was 20 months (CI 10.5–29.5) and with an expression ≥ 1% 28 months (CI 16.5–39.2), (p = 0.734). The median PFS of the patients with an expression of PD-L1 < 1% was 9 months (CI 6.3–11.6) and with an expression ≥ 1% 12 months (CI 9.8–14.2), not statistically significant (p = 0.112). The blood parameters had no significant impact on the OS. Conclusion In this retrospective cohort of stage III patients, the assumption that lack of PD-L1 expression represents a favorable prognostic factor after radio-chemotherapy vs. PD-L1 expression > 1% was not confirmed.

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Section: Similarities Of the Populationsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 88%

Evaluation of the prognostic impact of SP263-evaluated PD-L1 expression in patients with non-small cell lung cancer (NSCLC) stage III treated with radio-chemotherapy

Wagner¹,

Roeper²,

Heukamp³

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…95,96 Several immune cells and proteins are being evaluated for predicting immune-therapy efficacy, but neither a single feature nor more complex 'immunograms' have gathered enough evidence to be implemented in the clinical practice yet and immune profiling remains investigational. [97][98][99] Importantly, we do not know whether baseline tissue analyses can provide useful information, since CCRT may alter the TME. Performing translational research in locally advanced NSCLC is also challenging due to the paucity of tumor tissue available.…”

Section: Patient Selection and Predictive Biomarkersmentioning

confidence: 99%

Immunotherapy in unresectable stage III non-small-cell lung cancer: state of the art and novel therapeutic approaches

et al. 2022

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“…More recently, several post‐PACIFIC trial studies have investigated the favorability of using a CCRT plus durvalumab consolidation strategy. Several factors predicting durvalumab efficacy have been identified, including immunopathological factors, such as PD‐L1 status and CD8 + ‐tumor stroma‐infiltrating lymphocyte (TIL) density 10–12 . A post hoc analysis of the PACIFIC trial reported a PFS benefit in the durvalumab arm compared with the placebo arm, irrespective of PD‐L1 status 13 …”

Section: Introductionmentioning

confidence: 99%

“…Several factors predicting durvalumab efficacy have been identified, including immunopathological factors, such as PD-L1 status and CD8 + -tumor stromainfiltrating lymphocyte (TIL) density. [10][11][12] A post hoc analysis of the PACIFIC trial reported a PFS benefit in the durvalumab arm compared with the placebo arm, irrespective of PD-L1 status. 13 However, because tumor samples were mostly obtained at baseline, the impact of immunological changes achieved by CCRT on the ability of PD-L1 to predict consolidation therapy outcomes should be considered.…”

Section: Introductionmentioning

confidence: 99%

Predictive value of post‐treatment C‐reactive protein‐to‐albumin ratio in locally advanced non–small cell lung cancer patients receiving durvalumab after chemoradiotherapy

et al. 2022

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Backgrounds The PACIFIC trial established durvalumab consolidation therapy after concurrent chemoradiotherapy (CCRT) as the standard treatment for locally advanced non–small cell lung cancer (LA‐NSCLC). However, little is known about the predictive factors of durvalumab efficacy in this population. This study aimed to validate the predictive use of inflammation‐related parameters in patients with LA‐NSCLC treated with CCRT plus durvalumab. Methods We recruited 76 LA‐NSCLC patients who received CCRT followed by durvalumab from 10 Japanese institutions. The neutrophil‐to‐lymphocyte ratio (NLR), C‐reactive protein‐to‐albumin ratio (CAR), and prognostic nutrition index (PNI) were measured before (pre‐treatment) and 2 months after (post‐treatment) durvalumab induction. Cox proportional hazards analysis was used to examine prognostic factors associated with progression‐free survival (PFS) after durvalumab therapy. Results The median follow‐up time was 17 (range, 3.3–35.8) months. The median PFS and overall survival (OS) times were 26.1 and 33.7 months, respectively. Durvalumab was discontinued in 47 (61.8%) patients, with non‐infectious pneumonitis being the most common reason. Post‐treatment CAR (cutoff, 0.2) was a significant stratifying factor in survival comparison (<0.2 vs. ≥ 0.2, median PFS, not‐reached vs. 9.6 months. Log‐rank, p = 0.002). Multivariate analysis with a Cox proportional hazards model showed that post‐treatment CAR was an independent prognostic factor for PFS (hazard ratio, 3.16, p = 0.003). Conclusions This study suggests that post‐treatment CAR has predictive value for LA‐NSCLC patients treated with CCRT plus durvalumab consolidation therapy.

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Prognostic and predictive value of PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in locally advanced NSCLC treated with simultaneous radiochemotherapy in the randomized, multicenter, phase III German Intergroup lung Trial (GILT)

Cited by 12 publications

References 18 publications

Evaluation of the prognostic impact of SP263-evaluated PD-L1 expression in patients with non-small cell lung cancer (NSCLC) stage III treated with radio-chemotherapy

Evaluation of the prognostic impact of SP263-evaluated PD-L1 expression in patients with non-small cell lung cancer (NSCLC) stage III treated with radio-chemotherapy

Immunotherapy in unresectable stage III non-small-cell lung cancer: state of the art and novel therapeutic approaches

Predictive value of post‐treatment C‐reactive protein‐to‐albumin ratio in locally advanced non–small cell lung cancer patients receiving durvalumab after chemoradiotherapy

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