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Antonio Galvano
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P07 - Early Stage/Localized Disease - Imaging and Biomarkers (ID 116)
- Event: WCLC 2020
- Type: Posters
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P07.02 - Detection of Molecular Residual Disease (MRD) using ctDNA in NSCLC: A Systematic Review and Meta-Analysis (ID 3383)
00:00 - 00:00 | Presenting Author(s): Antonio Galvano
- Abstract
Introduction
Several liquid biopsy methods for circulating tumoral DNA (ctDNA) analysis enabling detection and assessment of post-treatment molecular residual disease (MRD) have been recently developed. Hence, clinical trials have explored strategies to detect MRD and its correlation with clinical outcomes in different solid tumors.
Methods
We performed a systematic review (MEDLINE, Cochrane database, meetings abstracts) and finally included in our meta-analysis four trials (Hu et al, Chauduri et al, GASTO1035-1018 and DYNAMIC) to better define the role of ctDNA detected in biofluids (plasma and urine) and MRD in relation to clinical outcomes in surgically resected Non-Small Cell Lung Cancer (NSCLC, stage I-IIIA, 8th ed. TNM). Pooled results according to ctDNA detection rate, 1-month disease- or relapse-free survival (DFS or RFS) rate and overall survival (OS) were obtained.
Results
Four studies for a total of 575 patients were included in our analysis. The pooled analysis showed a ctDNA detection rate of 34.6% (95% CI, 19.9 - 51.1). One month post-surgery ctDNA positivity was associated with a significant high risk for DFS/RFS (RR 4.89, 95% CI 0.05 – 0.91) with a long-term effect on mortality risk (RR 11.86, 95% CI 3.36 – 41.79; Figure 1).
Conclusion
Based on the results from our meta-analysis, detection of MRD using ctDNA in radically resected NSCLC was associated with a higher risk of recurrence or death. Our findings are supportive of MRD assessment becoming a surrogate clinical endpoint that could be further used in prospective clinical studies.
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P33 - Pathology - Immunotherapy Biomarker (ID 101)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P33.15 - TMB in the First-Line Setting of NSCLC: A Systematic Review with Indirect Comparisons Between PD-1 and PD-L1 Inhibitors (ID 3091)
00:00 - 00:00 | Author(s): Antonio Galvano
- Abstract
Introduction
Tumor mutational burden (TMB) has been deeply investigated either on tissue or blood as immune checkpoint inhibitors (ICIs) positive predictive biomarker in the frontline setting of advanced Non-Small Cell Lung Cancer (NSCLC). However, the clinical utility of TMB for identifying patients who may benefit from ICIs remains unclear.
Methods
We performed a systematic review (MEDLINE, Cochrane database, meetings abstracts) and finally included in our meta-analysis seven first-line randomized controlled trials (KEYNOTE-042, KEYNOTE-189, KEYNOTE-407, KEYNOTE-021, CHECKMATE-227, CHECKMATE 026, MYSTIC) evaluating the efficacy of standard platinum-based chemotherapy (CT) plus single or combination ICIs (PD-1 or PD-L1) versus CT alone according to TMB status (TMB-high or -low) either on tissue or blood. Here we present the indirect comparisons likening PD-1 versus PD-L1 agents according to objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). We estimated and indirectly compared pooled hazard ratios (HRs) and relative risks (RRs).
Results
Indirect comparisons for efficacy outcomes showed that, in the TMB-low subgroup, PD-1 inhibitors were associated with a statistically significant advantage over PD-L1 inhibitors in terms of ORR (RR 2.18, 95% CI 1.44-3.31), PFS (HR 0.54, 95% CI 0.34-0.85) and OS (HR 0.66, 95% CI 0.51-0.87), strongly suggesting the use of PD-1 agents strategy within the TMB-low population. As regards the TMB-high subgroup, anti-PD-1 were only associated with a survival benefit in term of PFS, however showing no substantial differences in term of ORR and OS when indirectly compared to anti-PD-L1 (Figure 1).
Conclusion
Despite the need for longer follow-up and further prospective investigation, the results of this indirect comparison meta-analysis seemed to suggest that PD-1 inhibitors, when indirectly compared to PD-L1 inhibitors, could be considered as a better option for the management of advanced NSCLC patients with low TMB.
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P48 - Small Cell Lung Cancer/NET - Chemo - IO (ID 236)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P48.10 - Chemo-Immunotherapy in the Frontline of Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Indirect Comparisons (ID 3368)
00:00 - 00:00 | Presenting Author(s): Antonio Galvano
- Abstract
Introduction
For decades platinum-doublet chemotherapy (CT) has represented the standard of care for extensive stage Small Cell Lung Cancer (ES-SCLC) patients. More recently, the addition of an immune checkpoint inhibitor (ICI) to standard CT has shown to improve survival in patients with treatment-naïve ES-SCLC.
Methods
The current work aims to assess any difference in both efficacy and safety profiles among different Immuno-Oncology (IO) agents in combination with platinum-based CT in ES-SCLC patients according to different ICIs subtypes. We performed a systematic review (MEDLINE, Cochrane database, meetings abstracts) and finally included in our metanalysis six first-line randomized controlled trials (Reck et al 2013, Reck et al 2016, IMpower 133, EA5161, KEYNOTE-604, CASPIAN) comparing the association of standard CT (carboplatin plus paclitaxel or cisplatin/carboplatin plus etoposide) with an ICI (ipilimumab, nivolumab, pembrolizumab or durvalumab) versus standard CT alone in ES-SCLC. Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR), 12-month duration of response rate (DORR), treatment-related adverse events (TRAEs) and discontinuation rates (DRs) were obtained.
Results
Conclusion
Although no clear advantage in terms of ORR was directly underlined, our pooled results showed how the addition of ICIs to CT significantly improved DORR (RR 4.45 , 95% CI 1.76 – 11.21), resulting in long term benefits in PFS (HR 0.80, 95% CI 0.73 – 0.86) and OS (HR 0.82, 95% CI 0.75 – 0.90) with no differences in terms of TRAEs or DRs. Of note, indirect comparisons according to the different IO strategies suggested a slight advantage in favor of both PD-1 and PD-L1 over anti-CTLA-4 agents in terms of efficacy outcomes along with no additional significant differences in the safety profile, respectively (Figure 1a-b). When indirectly comparing PD-1 with PD-L1 inhibitors, no relevant significant differences regarding both efficacy and safety endpoints were observed, with benefit trends only for DORR (RR 1.86, 95% CI 0.52 – 6.69) and DR (RR 0.49, 95% CI 0.15 – 1.61) in favor of anti-PD-1 over anti-PD-L1 (Figure 1c).
Based on the pooled results of our meta-analysis, the association of an ICI with CT confirmed to provide a survival benefit when compared to CT alone. Although chemo-immunotherapy would now represent an established standard for newly diagnosed ES-SCLC patients, establishing the optimal therapeutic options still addresses an unmet need in the clinical setting and predictive biomarkers eventually need to be identified.
