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Gilberto Lopes
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P1.06 - Epidemiology/Primary Prevention/Tobacco Control and Cessation (ID 692)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.06-018 - EGFR Mutations and ALK Gene Rearrangements: Changing Patterns of Molecular Testing in Brazil (ID 10068)
09:30 - 09:30 | Presenting Author(s): Gilberto Lopes
- Abstract
Background:
Lung cancer is the leading cause of cancer death worldwide. In Brazil, cancer is the second most common cause of death and there were an estimated 27,330 new cases of lung cancer in 2014. Targeted therapies have changed disease prognosis and current clinical guidelines advocate for testing all patients with advanced disease for EGFR mutations and ALK gene rearrangements. Access to this testing is often limited in the developing world. In the case of Brazil, there is limited data regarding the frequency of testing and the changes in patterns of testing overtime.
Method:
Observational, retrospective study involving practice patterns of over 2000 cancer physicians in Brazil. We obtained de-identified data from a commercial database which included 11,684 patients with non-small cell lung cancer treated between 2011 and 2016. We analyzed the frequency of EGFR mutation testing and ALK rearrangement testing.
Result:
11,684 patients were analyzed, of which all had stage IV lung adenocarcinoma. In the years ranging from 2011 to 2016 there was a significant increase in the frequency of testing for EGFR mutations overtime; from 13% in 2011 (287/2228) to 34% in 2012 (738/2142), 39% in 2013 (822/2092), 44% in 2014 (866/1972) to 53% in 2015 (1165/2184) and 58% in 2016 (626/1066). Testing for ALK rearrangements over that same time period also increased noticeably from no patients tested in 2011 and 2012, to 0.9% in 2013 (19/2092) 3% in 2014 (59/1972), 5% in 2015 (121/2184), 5% in 2016 (52/1066).
Conclusion:
To our knowledge this is the largest data analysis regarding changing practice patterns of molecular testing for lung adenocarcinoma over time in Brazil and Latin America. The frequency of testing for EGFR mutations and ALK gene rearrangement has increased over the last 5 years but is still below the current guidelines recommending that all patients with advanced disease be tested. Further understanding of the barriers to testing, will hopefully lead to national strategies for universal implementation of molecular testing.
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P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.07-024 - ISEND May Predict Clinical Outcomes for Advanced NSCLC Patients on PD-1/PD-L1 Inhibitors but<br /> Not Chemotherapies or Targeted Kinase Inhibitors (ID 9586)
09:30 - 09:30 | Author(s): Gilberto Lopes
- Abstract
Background:
We have shown that the iSEND model may be predictive of clinical outcomes for advanced NSCLC (aNSCLC) patients receiving nivolumab but little is known of its potential performance for patients on other PD-1/PD-L1 inhibitors (PD-1/PD-L1i), chemotherapies (Chemo) or Targeted Kinase Inhibitors (TKIs).
Method:
We evaluated clinical outcomes of 325 aNSCLC patients who received second-line PD-1/PD-L1i (nivolumab, pembrolizumab, or atezolizumb, n=203), first-line platinum followed by maintenance (Chemo, n=81), and TKIs (erlotinib, afatinib, or crizotinib, n=41). As described in our previous reports, the iSEND model (Sex, ECOG [Performance status], NLR [Neutrophil-to-Lymphocyte Ratio] & DNLR [Delta NLR = NLR after treatment - pretreatment NLR]) was developed. We stratified each treatment group by iSEND and compared progression free survivals (PFS) and clinical benefit rates (CBR) at 12+/-2 weeks in the iSEND Good vs. the iSEND Others (Intermediate and Poor).
Result:
Median follow-up was 9.5 (95% CI: 7.1-11.9), 11.7 (95% CI: 4.5-18.9) and 9.3 months (95% CI: 4.5-14.2), respectively for PD-1/PD-L1i, Chemo, and TKIs groups. In the PD-1/PD-L1i group, PFS was better in the iSEND Good than the iSEND Others with a median of 17.4 vs. 5.1 months, (HR: 0.32, 95% CI, [0.20-0.50], p<0.0001) (Figure 1). In contrast, PFS was not better in the iSEND Good in Chemo (HR, 0.69, 95% CI, [0.42-1.20], p=0.19) or TKIs (HR, 0.89, 95% CI, [0.43-1.84], p=0.75). The area under the curves (AUC) of the iSEND for CBR at 12+/-2 weeks for aNSCLC patients treated with PD-1/PD-L1i was 0.72, (95% CI: 0.65-0.79, p<0.0001). The AUCs of iSEND for CBR in Chemo and TKIs were not significant. Figure 1. Kaplan-Meier curves for PFS in PD-1/PD-L1i, Chemo, and TKIs stratified by iSEND Good vs. Others Figure 1
Conclusion:
In our single-institution retrospective cohort, the iSEND model showed a predictive potential for advanced NSCLC patients treated with PD-1/PD-L1i but not for those treated with Chemo or TKIs
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P1.07-025 - Correlating ISEND and Tumor Mutation Burden (TMB) with Clinical Outcomes of Advanced Non-Small Cell Lung Cancer (ANSCLC) Patients on Nivolumab (ID 9587)
09:30 - 09:30 | Author(s): Gilberto Lopes
- Abstract
Background:
We developed an algorithmic model namely, the iSEND (Sex, ECOG performance status, NLR [Neutrophil-to-Lymphocyte Ratio] & DNLR [Delta NLR =NLR posttreatment - pretreatment NLR]) to predict the clinical outcomes of aNSCLC patients receiving nivolumab. Performance of the iSEND has not been compared with other potential immunotherapy biomarkers like TMB.
Method:
We identified 36 aNSCLC patients who received nivolumab after platinum with commercial TMB reports. As described in our previous reports, the iSEND was used to categorize patients into good, intermediate, and poor groups. 36 matched patients were also categorized into high TMB: ≥ 20 m/Mb (mutations per megabase), intermediate TMB: 6-19 m/Mb, and low TMB: ≤5 m/Mb. We evaluated progression free survival (PFS), and overall survival (OS). Performances of the iSEND and TMB were correlated with clinical benefit at 12+/-2 weeks by receiver operating characteristic (ROC) curves.
Result:
The median follow-up was 18.4 months (95% CI: 10.1-26.7). There were 16 deaths. The number of patients from iSEND good, intermediate, and poor groups were 12 (33%), 18 (50%), and 6 patients (16%), respectively. The median overall survivals of iSEND good, intermediate, and poor groups were 15.7 (10.8-20.58), 10.3 (4.8-15.7), and 3.7 (0-7.8) months, respectively (p=0.00006). The median overall survivals for high, intermediate, and low TMB groups were unreached, 10.3 (4.7-15.9), and 12.4 (7.1-17.7) months, respectively. (p=0.211, Figure1) The area under ROC curve of the iSEND for clinical benefit at 12+/-2 weeks was 0.733 (p=0.025, 95% C.I.: 0.56-0.90). Four intermediate iSEND patients who had OS less than 6 months had low TMBs. Figure 1. Kaplan-Meier curves for Overall Survival by iSEND model and TMBFigure 1
Conclusion:
From a limited retrospective single institutional database, iSEND characterized the clinical outcomes of aNSCLC patients on nivolumab well and high TMB correlated with better outcomes. A larger cohort validation is encouraged to explore the mutual supplementary benefit for improved performance.
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P1.11 - Patient Advocacy (ID 697)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Patient Advocacy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.11-001 - Economic Impact of Immune Checkpoint Inhibitor Therapy in Brazil and Strategies to Improve Access (ID 7516)
09:30 - 09:30 | Author(s): Gilberto Lopes
- Abstract
Background:
Immunotherapy was elected by ASCO as the most important advance in Oncology in the last 2 consecutive years. Harnessing the immune system to fight cancer cells has already changed clinical practice. Nevertheless, the cost of immune checkpoint inhibitors is a limitation to their incorporation in several countries, including Brazil. The objective of this study was to estimate the economic impact of immunotherapy and make suggestions in order to improve access for patients who benefit the most from treatment.
Method:
We assessed Brazilian cancer epidemiology data and the international literature to estimate the number of eligible patients each year. The authors estimated the economic impact according to the local medication acquisition costs converted to US dollars. The median duration of the treatment was based upon the randomized clinical trials.
Result:
We assessed 3 different agents (and one combo) for 4 indications in the treatment of lung cancer. The results are summarized in the table below.Drug NSCLC 1L NSCLC 2L TOTAL Number of Eligible Patients (% of all cancer patients) Increase in Cancer Drug Total Expenditure Cost in the Public Health System Additional Cost Per Citizen LYG Cost per LYG Nivo NA 173.0 mi All Comers 173.0 mi -10%: 154.1 -20%: 135.1 4,733 (1.0) +21.6% +19.3% +16.9% $0.90 $0.77 $0.68 0.57 $99,467 Pembro 354.0 mi PD-L1>50% (monoTx) 898.5 mi PD-L1<50% (+chemo) 100.0 mi PD-L1>1% 1,352 mi -10%: 1,211 -20%: 1,070 16,362 (3.5) +169% +151% +134% $6.76 $6.06 $5.35 Mono 0.73 +chemo 0.55 2L 0.69 $156,164 $200,684 $49,007 Atezo NA 255.6 mi All Comers 255.6 mi -10%: 228.4 -20%: 201.2 4,733 (1.0) +32.0% +28.6% +25.2% $1.28 $1.14 $1.01 0.74 $103,095
Conclusion:
The current cost of immune checkpoint inhibitors is prohibitive in the public health system in Brazil. While the country’s GDP per capita is 78% lower than that of the US, immune checkpoint inhibitors have similar prices in both. Biomarker selection, posology and lower cost drugs help decrease the total economic impact of therapy. Price discrimination and volume discounts would help improve access. Further studies and discussion with all stakeholders is needed to identify patients who would benefit the most and to implement strategies to increase access to these potentially life-saving therapies.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-006 - How Many Years of Life Have We Lost in Brazil Due to the Lack of Access to Anti-EGFR TKIs in the National Public Health System? (ID 7514)
09:30 - 09:30 | Author(s): Gilberto Lopes
- Abstract
Background:
Lung cancer is the fourth most common cancer in Brazil with 28,220 new cases in 2017. It is the main cause of cancer-related deaths with 23,393 deaths in 2013. In the 2000s, better understanding of molecular pathways led to the development of targeted treatments. The introduction of EGFR tyrosine kinase inhibitors (TKI) led to significant improvements in Response Rate and Progression-Free Survival for patients with activating mutations. Nevertheless, this treatment is not available in the Brazilian Public Health System based upon its costs andthe absence of Overall Survival gain in randomized clinical trials. The aim of this study was to assess the potential number of life-years lost and the cost associated with lack of treatment.
Method:
We estimated the number of eligible cases for treatment using epidemiological data from the National Cancer Institute (INCA) plus the national database on the frequency of EGFR gene mutations since July 2010 (gefitinib approval in Brazil). We based the differences in survival between patients treated with EGFR TKIs and chemotherapy using the curves of The Lung Cancer Mutation Consortium. The costs of TKI treatment were based on the national reference ($1,200 monthly) and was compared with the amount reimbursed by the Brazilian Public Health System for chemotherapy ($350 monthly).
Result:
The number of eligible cases for EGFR TKIs in the Brazilian Public Health System is around 2,224 patients each year. Since gefitinib approval, the estimated number of years of life lost due to the lack of access to EGFR TKIs was 2,668 annually. Considering only drug acquisition costs, we need nearly 150 million dollars to incorporate TKIs into the public health care system. The cost per incremental life-year gained over chemotherapy was 585 dollars. Although our analysis does not consider quality-of-life, the cost of one life-year gain is lower than three times the Brazilian GDP per capita (approximately 35,000 dollars).
Conclusion:
The lack of access to EGFR TKIs cost more than 18,676 years of live in Brazil in the past 7 years. Treatment would also be cost-effective.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 3
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-037 - Developing a Predictive Clinical Outcome Model for Advanced Non-Small Cell Lung Cancer Patients<br /> Receiving Nivolumab (ID 9453)
09:30 - 09:30 | Author(s): Gilberto Lopes
- Abstract
Background:
Despite significant improvement of clinical outcomes of the patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors, our knowledge of optimal predictive and prognostic biomarkers are still evolving.
Method:
We retrospectively evaluated 159 advanced NSCLC patients who received nivolumab after platinum-based chemotherapy. We correlated several variables with progression free survival (PFS) to develop the iSEND model (Sex, ECOG [Performance status], NLR [Neutrophil-to-Lymphocyte Ratio] & DNLR [Delta NLR = NLR after treatment - pretreatment NLR]). We categorized the patients into good, intermediate, and poor iSEND groups and evaluated clinical outcomes of each group. Performance of iSEND model was evaluated at 3, 6, 9, and 12 months by receiver operating characteristic (ROC) curves. We performed bootstrap internal validation to evaluate the predictive performance of the iSEND model by using the split-sample validation technique. We used logistic regression to correlate different iSEND groups and clinical benefit.
Result:
The median follow-up was 11.5 months (95% C.I.: 9.4-13.1). There were 50 deaths and 43 other progressions without death. The 3-, 6-, 9-, and 12-months PFS rates were 78.4%, 63.7%, 55.3%, and 52.2% in the good group, 79.4%, 44.3%, 25.9% and 19.2% in the intermediate group, and 65%, 25.9%, 22.8%, and 17.8% in the poor group, respectively. (Figure 1) Time-dependent area under curves (AUC) of the iSEND model for PFS at 3-, 6-, 9-, and 12-months were 0.718, 0.74, 0.746, and 0.774. The poor iSEND group had significant correlation with progressive disease compared to the good group at 12+/-2 weeks. Figure 1. Kaplan-Meier curves for Progression Free Survival of different iSEND model groups Figure 1
Conclusion:
The iSEND model is an algorithmic model that can categorize clinical outcomes of advanced NSCLC patients receiving nivolumab into good, intermediate, or poor groups and may be useful as a predictive model.
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P2.07-054 - Cost-Effectiveness of Pembrolizumab as First-Line Therapy for Advanced Non-Small Cell Lung Cancer (ID 7510)
09:30 - 09:30 | Author(s): Gilberto Lopes
- Abstract
Background:
Immunotherapy is changing the therapeutic perspective and expectations for solid tumors and constitutes a major therapeutic advance for advanced non-small cell lung cancer (NSCLC). We assessed the cost-effectiveness of pembrolizumab (anti-PD-1 antibody) as compared to platinum-doublet chemotherapy as first-line therapy for advanced NSCLC.
Method:
We developed a Bayesian Markov model of disease states with a 5-year horizon. We retrieved survival, progression, and safety data comparing pembrolizumab to contemporaneous platinum-doublet chemotherapy as first-line therapy for PD-L1 expression equal to or greater than 50%, EGFR non-mutated, ALK non-translocated lung carcinoma patients. Published estimated US and UK costs were applied to inform the incremental cost-effectiveness ratio (ICER). We estimated costs in USD and summarized effectiveness as discounted quality-adjusted life-years (QALYs).
Result:
Patients treated with pembrolizumab accumulated 0.65 QALYs (95% credible interval [95% CrI] 0.5-0.91) as compared to 0.19 QALYs (95% CrI 0.16-0.22) to 0.32 QALYs (95% CrI 0.27-0.37) for those treated with platinum-doublet chemotherapy. From a current US cost perspective, ICERs varied from $173,000 (95% CrI $163,000-$183,000) to $201,000 (95% CrI $182,000-232,000) for one end-of-life (EoL) adjusted QALY, while from a British National Health System (NHS) perspective, ICERs varied from $154,000 (95% CrI $144,000-$166,000) to $193,000 (95% CrI $165,000-$248,000) per EoL adjusted QALY gained.
Conclusion:
At current price, pembrolizumab is not cost effective considering the usual NICE threshold in the UK. In the US, these numbers would be considered cost-effective according to the WHO definition.
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P2.07-055 - Indirect Comparison between Immune-Checkpoint Inhibitors for 2nd Line Non-Small Cell Lung Cancer – a Network Meta-Analysis (ID 7513)
09:30 - 09:30 | Author(s): Gilberto Lopes
- Abstract
Background:
Treatment with immune checkpoint inhibitors (ICIs) improves overall survival with lower toxicity when compared to classic chemotherapy in the management of advanced non-small cell lung cancer (NSCLC). While emerging, the role of PD-L1 expression as a biomarker remains controversial. In addition, all clinical trials that included previously treated patients compared ICIs with docetaxel and there is a lack of data comparing each agent against each other. This network meta-analysis aims to (i) compare overall survival (OS) with nivolumab, pembrolizumab, and atezolizumab against docetaxel in previously treated advanced non-small cell lung cancer (NSCLC) patients and (ii) to perform indirect comparisons between ICIs in the PD-L1 unselected population and by PD-L1 expression levels.
Method:
We searched Pubmed for randomized controlled trials comparing the ICIs nivolumab, pembrolizumab and atezolizumab in the treatment of patients with previously treated advanced NSCLC. Two independent reviewers screened each study. We performed network meta-analyses of survival outcomes in the PD-L1 unselected population and by PD-L1 expression levels <1%, ≥1%, ≥5%, ≥10%, and ≥50%. Head-to-head indirect comparisons of nivolumab, pembrolizumab and atezolizumab were constructed and treatment rankings provided in terms of SUCRA and probability that a treatment is best. We also assessed the potential survival benefits of selecting patients by PD-L1 expression level as compared to a PD-L1 unselected population.
Result:
Five trials with 3,024 total patients were included in the meta-analysis. ICIs improved OS in previously treated advanced NSCLC patients across PD-L1 expression levels compared to docetaxel with HRs of 0.70 (95% CrI 0.61-0.81), 0.79 (0.65-0.97), 0.67 (0.57-0.77), 0.55 (0.44-0.69), 0.43 (0.30-0.63), and 0.49 (0.37-0.63) for PD-L1 expression levels as follows: unselected, <1%, ≥1%, ≥5%, ≥10%, and ≥50%. However, for individual ICIs nivolumab and atezolizumab in PD-L1<1%, there was only weak evidence of benefit with HR of 0.77 (0.57-1.04) and 0.81 (0.62-1.08) respectively compared to docetaxel. Nivolumab, pembrolizumab and atezolizumab showed little survival differences between each other (nivolumab vs pembrolizumab HR 0.94 (0.63-1.39), nivolumab vs atezolizumab 0.91 (0.62-1.35), and pembrolizumab vs atezolizumab 0.97 (0.68-1.41) in PD-L1 ≥1%). When interpreting these data, it is important to note that while nivolumab and pembrolizumab trials used tumor cells for PD-L1 cutoffs, atezolizumab used both tumor and/or immune cell cut-offs and PD-L1≥50% in atezolizumab trials comprised patients with tumor cell PD-L1≥50% or immune cell PD-L1≥10%.
Conclusion:
ICIs improve survival across PD-L1 expression levels compared to docetaxel. None of the available ICIs, nivolumab, pembrolizumab and atezolizumab, seem to be better than the others.
