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Pedro Aguiar Jr
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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 | Presenting Author(s): Pedro Aguiar Jr
- 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 | Presenting Author(s): Pedro Aguiar Jr
- 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: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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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 | Presenting Author(s): Pedro Aguiar Jr
- 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 | Presenting Author(s): Pedro Aguiar Jr
- 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.
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-019 - Activity of PARP Inhibitor in NSCLC with Germline and Somatic Mutation and in Silico Chemotherapy Lethality (ID 9740)
09:30 - 09:30 | Author(s): Pedro Aguiar Jr
- Abstract
Background:
Challenges in Precision and Personalized Medicine with interpatient variation needs individualized protocols. PARP Inhibition may be one modality of treatment of NSCLC, as coadjutant to chemotherapy.
Method:
A 66 years old male has been diagnosed with lung adenocarcinoma since 02-06-2016, c T4 c N1 c M1a (pleura and pericardium), had been exposed to carboplatin and pemetrexed for 6 cycles (January to March 2016) with disease progression, and peripheral neuropathy. He didn’t have EGFR mutation, ALK translocation, MET/RET or ROS-1 FISH alterations. He had been treated with radiation therapy from September to November 2016 with 60 Gy, IMRT, and after he received Nivolumab, from November 2016 to Abril 2017 with radiological progression. He had been tested by RCGG in May 2017 looking for circulating tumor cells in vitro (the culture contains all substances measured to apoptotic ability using oncogene apoptosis kit; the result is confirmed by cultures of the tumor or circulating tumor cells), Idengen (inherited hot-spot mutations), and Guardiant 360 by liquid biopsy (circulating DNA sequencing somatic mutations).
Result:
With the Idengene test, he has had PALB2 inherited mutation germline with possible pathogenic significance, BRCA1 and BRCA2 with unknown pathogenic significance. Also, he had NBN, PTCH2, and PTEN as possible pathogenic significance. With the Guardiant 360 test, he had BRCA1, C24Y, NF1, R416Q somatic mutations. With the RGCC test, the specific tumor appears to have resisting populations because of the MDR1 overexpression that can be reversed using inhibitors of ABCG2 pumps. Also, the neoplastic cells have the greatest sensitivity in the alkylating agent (cisplatin, mitomycin), in the tubulin dimmer polymerization inhibitors (Vinorelbine). Inhibitor of Akt/mTOR pathway can be used, as Everolimus, temsirolimus. He has partial sensibility to nucleus spindle stabilizer I (paclitaxel, docetaxel), II (vincristine, vinblastine), and nucleoside analogues (methotrexate, gemcitabine, pemetrexed). Therefore he has been exposed to oral Olaparib 300 mg BID, intravenous Gemcitabine 600 mg/m2, and oral vinorelbine 60mg/m2 weekly both., with good tolerability, and improvement of Performance Status.
Conclusion:
PARP Inhibitor can be a target therapy in personalized medicine, guided by PALB2 / BRCA 1 / 2 mutations in codons inherited and / or somatic mutations, in addition to gemcitabine and vinorelbine in lung adenocarcinoma resistant to platinum/pemetrexed. The addition of Olaparib was possible in this patient, and feasible with a good tolerability, maybe impacting the outcome. More studies related to PARP inhibitor and NSCLC need to be developed.
