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Gilberto Lopes
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-61 - iSEND Model as a Predictor of Efficacy in Immune Checkpoint Inhibitors for Non-Small Cell Lung Cancer: Fukushima Cohort (Now Available) (ID 1689)
08:00 - 18:00 | Author(s): Gilberto Lopes
- Abstract
Background
The expression of PD-L1 in tumor tissue and the number of gene mutations (TMB) in tumor tissue have been investigated as predictors of the efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer. However. In actual clinical practice, it is difficult to perform these tests in all cases.
Therefore, we are searching for an effect prediction marker that can be done easily and inexpensively. Wungki Park et al. constructed the iSEND model as a therapeutic effect predictor and showed its usefulness. We examined the usefulness of iSEND model for non-small cell lung cancer patients who received PD-1 / PD-L1 inhibitor at our institution.
Method
We retrospectively examined the usefulness of the iSEND model in 56 patients with non-small cell lung cancer who were treated with PD-1/PD-L1 inhibitor in our department after the second treatment. The iSEND model uses patient background and blood tests. Calculated and scored using gender, ECOG performance status, NLR before treatment and after treatment (Neutrophi-to-Lymphocyte Ratios), and divided into three group. For each group, we statistically compared the clinical course such as overall survival and recurrence-free survival.
Result
In the analysis by Wungki Park et al. , The iSEND Poor group has a median overall survival of 4.0 months and 15.9 months, respectively, compared with the iSEND Good group (p = 0.0002), and the median recurrence free period is 1.6 months and 2.6 months, respectively. Months (p = 0.0045), and each showed a significant difference. In our study, no statistically significant difference was found, but a trend similar to the analysis of Wungki Park et al.
Conclusion
In this study, it is suggested that the iSEND model may be useful as a predictor of the effect of PD-1/PD-L1 inhibitor.
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EP1.01-88 - Next-Generation Sequencing in Hispanic Patients with Advanced Lung Cancer and Correlation with Response to Immunotherapy (Now Available) (ID 2784)
08:00 - 18:00 | Author(s): Gilberto Lopes
- Abstract
Background
Cancer is a leading cause of death among Hispanics (HISP); the largest ethnic minority in the United States (17% of the total population). With the approvals of checkpoint immunotherapy in advanced lung cancer, many patients (pts) are starting to see long-lasting remissions and longer survival rates. However, response to a given treatment often depends on the tumor’s genomic profile. Our aim was to analyze NGS results for HISP pts living in the US in an effort to better understand this population’s genomic profile and prognosis.
Method
Retrospective analysis on pts with biopsy proven advanced NSCLC who received checkpoint immunotherapy at two large institutions in the US. Patient charts were reviewed to obtain data on demographic characteristics including race, gender, age, and smoking history. Next generation sequencing (NGS) results were obtained from Guardant Health and Foundation One testing in blood and in tissue, respectively. We assessed progression-free survival (PFS) and overall survival (OS) associated with outcome.
Result
Seventy HISP pts receiving immunotherapy underwent NGS testing from 10/2013 to 4/2018. 46% were male, 76% were smokers, 89% had adenocarcinoma, and 39% were PD-L1 positive (with 67% of those having TPS ≥ 50%). Thirty pts (43%) had one genetic aberration (GA), and 15 pts (22%) had >5 GA. The most frequent actionable GA was EGFR mutation (26%) and nonactionable mutation was KRAS (40%). Other less common GA were BRAF (10%), MET (10%), and STK11 (9%).
Survival
1 Genetic Aberration
>5 Genetic Aberrations
P value
Median PFS
3.57m
3m
0.2767
Median OS
14.96m
3.8m
0.0117
Conclusion
The presence of >5 GA (actionable and nonactionable) on NGS testing was associated with worse OS when compared to pts with one GA. There was no difference in PFS. In addition, PD-L1 incidence in HISP pts is high with a larger proportion of pts expressing ≥ 50% TPS compared to what is reported for NHW. Given the numerous nonactionable GA encountered, it is clear that continued development of targeted therapies would keep benefitting pts. Increased NGS profiling in HISP pts could potentially broaden treatment and clinical trial options to serve this purpose.
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MA07 - Clinical Questions and Potential Blood Markers for Immunotherapy (ID 125)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:David R Spigel, Roberto Ferrara
- Coordinates: 9/08/2019, 13:30 - 15:00, Vancouver (2003)
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MA07.02 - Early Change of dNLR Is Correlated with Outcomes in Advanced NSCLC Patients Treated with Immunotherapy (Now Available) (ID 2676)
13:30 - 15:00 | Author(s): Gilberto Lopes
- Abstract
- Presentation
Background
The [neutrophils/[leucocytes-neutrophils] ratio (dNLR) correlates with immune checkpoint inhibitors (ICI) outcomes in advanced non-small cell lung cancer (aNSCLC) patients. Significance of early dNLR change after the first course of ICI is unknown.
Method
Patients with NSCLC treated with ICI (PD(L)1+/-CTLA4) between Nov. 2012 and Jun. 2018 at 16 EU/US centers were included. A control group treated with chemotherapy (CT) only was also evaluated (NCT02105168). dNLR was collected at baseline (B) and at cycle 2 (C2). Patients were categorized as low vs high dNLR at each timepoint (defined as < vs > 3, as previously done), and the change between B and C2 (good = low at both timepoints, poor = high at both timepoints, mixed = different at each timepoint).
Result
1485 patients treated with ICI were analyzed. PDL1 was negative in 162 (11%), 1-49% in 178 (12%), ≥50% in 201 (14%), and missing in 944 (64%). dNLR at B and C2 did not associate with PD-L1 status.
At baseline, dNLR was high in 509 (34%) patients and associated with worse PFS compared to those patients with low dNLR at baseline (HR 1.56, P<0.0001) and OS (HR 2.02, P<0.0001). At C2, dNLR was high in 484 (34%) and similarly associated with worse outcomes compared to patients with low dNLR at C2 (PFS HR 1.64, P<0.0001; OS HR 2.13, P<0.0001).
Between B and C2, dNLR remained low in 804 (56%, « good ») or high in 327 (23%, « poor ») or changed in 310 pts (22%, « intermediate »). Those with a good dNLR demonstrated mPFS 5.3, mOS 18.6 mo), followed by those intermediate with mixed dNLR (mPFS 3, mOS 9.2 mo), and finally poor dNLR (mPFS 2, mOS 5mo). Outcomes were independant of PD-L1 expression (adjusted HR for PFS 1.94 for intermediate and 3.16 for poor groups, compared to good dNLR group, P<.001; adjusted HR for OS was 2.08 for intermediate and 3.67 for poor groups, P<0.001).A bootstrap tested the stability of OS/PFS prediction (P<0.001).
In the chemo-cohort (n=173), high C1-dNLR (n=81, 47%) was not associated with OS (P=0.84).
Conclusion
dNLR at baseline, at cycle 2, and the change between these two timepoints associated with outcomes in patients treated with immunotherapy independent of PD-L1, but not in patients treated with chemotherapy alone. dNLR is specifically prognostic in the context of immunotherapy.
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-67 - First-Line Immune Checkpoint Inhibitors in Advanced Non-Small-Cell Lung Cancer (NSCLC) – A Network Meta-Analysis by PD-L1 (ID 2544)
09:45 - 18:00 | Presenting Author(s): Gilberto Lopes
- Abstract
Background
Emerging trials suggested survival benefits of first-line immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy in advanced NSCLC. However, little is known about the head-to-head comparisons of different ICIs and their relative effects at different PD-L1 expression levels. Here, we compared overall survival (OS) with ICIs head-to-head in a network meta-analysis and computed rankings of ICIs by PD-L1 expression levels.
Method
PubMed and conference abstracts were searched for randomized clinical trials evaluating first-line ICI alone or in combination with chemotherapy in advanced NSCLC. We excluded studies assessing other trigger biomarkers (e.g. TMB). Bayesian network meta-estimates were computed by pooling reported OS hazard ratios (HRs) on the logarithmic scale and incorporation of both within and between studies heterogeneity. Treatment rankings by PD-L1 expression levels were compared in terms of surface under the cumulative ranking curve (SUCRA), probability best, probability better than chemotherapy, and posterior HR with corresponding 95% credible interval (CrI).
Result
Seven trials were included in network meta-analysis. Pembrolizumab+chemotherapy was ranked to have the best OS benefit with HR ≤0.60 and >99% probability to outperform standard chemotherapy across all PD-L1 expression categories. Atezolizumab+chemotherapy and pembrolizumab monotherapy showed >95% probability to outperform standard chemotherapy in PD-L1 ≥50%. Nivolumab monotherapy showed little to no benefit across PD-L1 categories. Head-to-head comparisons of pembrolizumab+chemotherapy versus pembrolizumab monotherapy were HR 0.76 (0.48-1.19) for PD-L1≥50%. Detailed meta-estimates by PD-L1 expression for ICI alone or in combination with chemotherapy versus standard chemotherapy are provided in table below.
ConclusionTreatment
PD-L1 expression
OS HR (95% CrI)
Probability better than standard chemotherapy
Pembrolizumab+chemotherapy
≥50%
0.51 (0.34-0.75)
> 99%
1-49%
0.56 (0.39-0.81)
> 99%
≥1%
0.55 (0.41-0.73)
> 99%
<1%
0.60 (0.42-0.85)
> 99%
Atezolizumab+chemotherapy (include immune-cell cut-offs)
≥50%
0.70 (0.47-1.05)
96%
1-49%
1.03 (0.74-1.42)
43%
<1%
0.83 (0.66-1.06)
93%
Pembrolizumab
≥50%
0.67 (0.53-0.83)
> 99%
1-49%
0.92 (0.69-1.23)
73%
≥1%
0.81 (0.63-1.04)
95%
Nivolumab
≥50%
0.90 (0.60-1.36)
70%
≥1%
1.08 (0.80-1.46)
30%
Pembrolizumab+chemotherapy demonstrated best survival benefit compared to other ICIs across all PD-L1 expression levels in the first-line treatment of advanced NSCLC.
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P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.16-15 - Survival and Clinical Immunotherapy Outcomes in Hispanic Patients vs Non-Hispanic White Patients with Non-Small Cell Lung Cancer (Now Available) (ID 1514)
10:15 - 18:15 | Author(s): Gilberto Lopes
- Abstract
Background
The number of Hispanic (HISP) patients (pts) enrolled in immunotherapy (IMMUNO) trials is minimal or non-existent in non-small cell lung cancer (NSCLC). It’s well known that HISP pts with NSCLC have not only a different genomic profile than Non-Hispanic Whites (NHW)- like higher expression of EGFR mutations- but also better outcomes than NHW (“Hispanic Paradox”); thus the need to validate outcomes in HISP pts treated with IMMUNO.
Method
We present data in 436 NSCLC pts treated with IMMUNO at 5 large institutions (3 in the US, 2 in Latin America). The agents evaluated include: nivolumab, pembrolizumab and atezolizumab. 256 pts were HISP and 180 pts were NHW. Most of the pts were treated with single agent therapy as second line or beyond while a small group of pts were treated as first line. The primary endpoints of the study were: response rate (ORR), progression free survival (PFS) and overall survival (OS). Secondary endpoints were disease control rate (DCR), PD-L1 expression and others.
Result
The results are consolidated in the table below.
Hispanics (n=256)
NHW (n=180)
p value
Sex (males)
52%
45%
0.2059
ORR
First Line
35%
30%
0.6590
Second Line
18%
19%
0.3236
Adeno
22%
24%
0.6714
SQCC
24%
23%
1.0000
PDL1 (+)
29%
32%
0.4839
PDL1 (-)
5%
17%
0.3040
Disease Control Rate: ORR+SD (DCR)
Adeno
68%
67%
0.8989
SQCC
67%
46%
0.0777
Median PFS
4m
4m
0.7509
Median OS
22m
22m
0.2004
There were no statistical significant differences among HISP and NHW pts regarding ORR, DCR, PFS, OS, and responses according to PD-L1 status.
Conclusion
No significant differences were found in the clinical outcomes between these 2 ethnic groups despite the “Hispanic Paradox” and expected genomic differences; however pts with actionable mutations were excluded as they usually do not get IMMUNO as first or second line; an approach that might change after IMPOWER 150. This is the largest comparison of NSCLC immunotherapy outcomes in HISP vs NHW pts. These results are comparable to the ones seen in Checkmate and Keynote studies. As expected, higher response rates were seen in first line therapy and pts with PD-L1 (+) status. Further comparisons will be better addressed by a larger prospective study.
