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Petros Christopoulos
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P75 - Immunotherapy (Phase II/III Trials) - Misc. Topics (ID 248)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P75.04 - Advanced Lung Cancer Inflammation Index (ALI), Neutrophil-to-Lymphocyte Ratio (NLR), and PD-(L)1 Inhibitor Efficacy in NSCLC (ID 3415)
00:00 - 00:00 | Presenting Author(s): Petros Christopoulos
- Abstract
Introduction
Improved biomarkers of immune checkpoint inhibitor (ICI) efficacy are a main objective of research in thoracic oncology currently. The neutrophil-to-lymphocyte ratio (NLR) and advanced lung cancer inflammation (ALI) index (body mass index*serum albumin/NLR) reflect systemic inflammation and are easily reproducible in clinical practice.
Methods
The potential value of ALI and NLR as immunotherapy (IO) biomarkers was analyzed in a discovery cohort of 348 advanced NSCLC patients treated with PD-(L)1 inhibitors in the Heidelberg University Hospital, followed by validation in an independent cohort of 590 patients with similar characteristics from 25 cancer centers in Greece (experimental cohorts). An additional control cohort of 444 therapy-naive NSCLC patients treated with first-line platinum-based chemotherapy without subsequent targeted or IO drugs from Heidelberg was also examined in order to discern predictive from prognostic effects. ALI and NLR were dichotomized at the bibliographic cut-offs of 18 and 5, respectively, which corresponded to the median value of our untreated patients (18.03 and 5.00). The relationship of overall survival from start of IO treatment (OS) with other parameters was analyzed with Cox regression models, including calculation of the Harrel’s C-index in both ICI-treated cohorts for validation of results.
Results
High ALI values (>18) were significantly associated with longer OS for patients receiving ICI monotherapy in both the training (hazard ratio (HR)=0.43, 95% confidence interval (CI) 0.31-0.61, p<0.0001, n=245) and validation cohorts (HR=0.70, 95% CI 0.52-0.95, p=0.0236, n=507). In contrast, no relationship between ALI and OS was observed for patients treated with chemoimmunotherapy (HR=1.10 with p=0.82, and HR=0.83 with p=0.74 in the two cohorts, respectively). In the control cohort of chemotherapy, the association between ALI and OS was less pronounced compared to the discovery cohort (HR=0.70, 95% CI 0.58-0.85, p=0.0003), and showed a significant interaction with the type of treatment (ICI vs. chemotherapy, p<0.0001) in combined analysis of the two cohorts. The relationships of NLR and PD-L1 tumor proportion score (TPS, absent vs. 1-49 vs. 50-100) with OS were significant also in case of ICI monotherapy only (HR=0.50 with p<0.0001, and HR=0.75 with p=0.013, respectively, in the training cohort), but not with chemoimmunotherapy (p>0.70 for both markers in both cohorts). Among patients treated with ICI monotherapy in both experimental cohorts (n=752), the effect of ALI on OS (HR=0.51, p=6*10‑10) was stronger than that of the NLR (HR=0.55, p=3*10-8) and PD-L1 TPS (HR=0.71, p=10-4). In a multivariable analysis for OS together with other parameters significant in univariable testing, ALI emerged as an independent predictor with the strongest impact (HR=0.48 with p=0.002 for high ALI, HR=0.62 with p=0.005 for first- vs. subsequent-line immunotherapy, HR=0.79 with p=0.023 for higher PD-L1 TPS, and HR=0.83 with p=0.45 for low NLR).
Conclusion
The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-(L)1 inhibitors alone, but not in combination with chemotherapy. Its association with outcome appears to be stronger than that of other widely used parameters, such as the PD-L1 TPS and NLR, and could therefore facilitate more accurate predictions. Reliable markers for chemoimmunotherapy outcomes remain an unmet need in NSCLC.
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P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P84.03 - GLASS: Global Lorlatinib for ALK(+) and ROS1(+) Retrospective Study: Real World Data of 123 NSCLC Patients (ID 3172)
00:00 - 00:00 | Author(s): Petros Christopoulos
- Abstract
Introduction
Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib.
Methods
This is an international, multicenter, retrospective study, which aimed to describe the efficacy and safety of lorlatinib in previously treated ALK/ROS1(+) NSCLC. All patients were treated through an early access program, when no other targeted therapy was available.123 patients were enrolled retrospectively (data cut-off 1/1/2019). Outcome and response were defined by each investigator upon RECIST 1.1 criteria.
Results
From March 2015 to January 2019, 106 ALK(+) and 17 ROS1(+) patients were recruited from 8 different countries. The ALK(+) cohort included 50% males, 73% never-smokers and 68% with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60% and 62%, with disease control rates (DCR) of 91% and 88% respectively. Mean duration of therapy (DoT) was 23.9±1.6 months and median overall survival (mOS) was 89.1±19.6 months. ROS1 cohort enrolled 53% males, 65% never-smokers and 65% had brain metastases. EC and IC RR were 62% and 67% with DCR of 92% and 78% respectively. Median DoT was 18.1±2.5 months and mOS of 90.3±24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters.
The most common adverse events of any grade were peripheral edema (48%), hyperlipidemia (47%), weight gain (25%) and fatigue (30%). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18% of patients.
Conclusion
Lorlatinib shows outstanding extracranial and intracranial efficacy in ALK or ROS1(+) NSCLC. The observed mOS of 89±19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90±24 months is unprecedented for ROS1(+) NSCLC.
