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Pedro De Marchi
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-09 - Efficacy and Safety of Osimertinib After Prior EGFR TKI: Analysis of Patients Underrepresented in Randomized Clinical Trials (ID 14036)
16:45 - 18:00 | Author(s): Pedro De Marchi
- Abstract
Background
Osimertinib is a new standard of care in non-small cell lung cancer (NSCLC) after progression to an EGFR TKI in the presence of T790M mutation. Following results of the phase III study AURA 3, which led to the approval of osimertinib worldwide, we have conducted ASTRIS in Brazil.
a9ded1e5ce5d75814730bb4caaf49419 Method
This is a phase IV, international, multicentric, open trial, with the aim of confirming the efficacy and safety of osimertinib at a dose of 80 mg daily, orally. Eligible patients presented with diagnosis of T790M-positive NSCLC on progression after prior EGFR TKI. Herein, we present the Brazilian experience at ASTRIS, including subsets that were underrepresented in the phase III trial.
4c3880bb027f159e801041b1021e88e8 Result
Eighty-eight patients were enrolled in Brazil between August 2015 and March 2017. The median age was 64 years (34-89), and most were females (66%). Fifty-four patients (61%) had received prior therapy with erlotinib, forty-two (48%) with gefitinib, and 3 (3%) with afatinib. Nineteen patients (22%) were exposed to a EGFR TKI more than 6 months before enrolment. Importantly, 11 patients (12.5%) presented with a PS of 2, 23 (26%) presented with brain metastases, and 3 with leptomeningeal disease. Exon 19 deletions were the most common primary mutation in EGFR, present in 55 cases (62.5%), followed by L858R in 24 cases (27%). Tumor samples were acquired from the primary tumor in 14 cases (45%) and in a metastatic site in 16 (52%); all other cases had T790M detected at plasma. After a median follow-up of 9.3 months, 26 progression events and 23 deaths were documented. The response rate was 58.2% (95%CI 46.6-69.2), and median progression-free survival was 9.4 months (95%CI 8.2-not reached). The 12-month overall survival was 69.7% (95%CI 56.5-79.6). Thirty patients (34%) presented an adverse event, 14 of which led to dose modification and 5 to treatment discontinuation. The most common adverse events were infection in 14 cases (15%), gastrointestinal and hematologic (4 cases each). Nineteen patients (22%) had a serious adverse event, mostly infections (14 cases).
8eea62084ca7e541d918e823422bd82e Conclusion
The profile of patients enrolled in Brazilian institutions highlights the presence of cases with poor PS, which was excluded in the AURA 3 trial. Despite these features, the efficacy and safety of osimertinib was confirmed, suggesting that results could be extrapolated to a broad range of subsets. This study also underscores the role of liquid biopsy in the detection of T790M, in detriment to tumor re-biopsy.
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P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.01-12 - EGFR Mutation and Targeted Therapies: Difficulties and Disparities in Access to NSCLC Treatment in Brazil. (ID 14236)
12:00 - 13:30 | Author(s): Pedro De Marchi
- Abstract
Background
Non-small cell lung cancer (NSCLC) is the most prevalent lung cancer subtype, commonly presenting as advanced disease at diagnosis. Epidermal growth factor mutation (EGFRm) occurs in 10-15% of Western population with advanced NSCLC and its management includes the use of mutation-driver EGFR tyrosine kinase inhibitors (EGFR-TKIs). In Brazil, patients with EGFRm NSCLC may face barriers to access EGFR test and directed-therapy; otherwise, there is a lack of national clinical data addressing this issue. This study intended to evaluate the access to molecular EGFR testing, initial treatment, and its respective response in this patients setting in public and private institutions in Brazil.
a9ded1e5ce5d75814730bb4caaf49419 Method
In this retrospective cohort, patients with newly diagnosed advanced NSCLC between January and December 2014 were consecutively included. Data were collected from medical records of 10 Brazilian cancer institutions, and recorded in electronic clinical report form. Demographic data, medical history, tumor staging, pathological characteristics, treatments and outcomes were collected and analyzed. For each patient, maximum follow-up was 36 months.
4c3880bb027f159e801041b1021e88e8 Result
402 patients from 8 different Brazilian states were enrolled, and 391 were included in the analysis, being 236 men (60.4%). Median age was 64 years, 80% have been treated in the public and 20% in private health system; 74.9% (n = 293) were former or current smokers. The most frequent histological subtypes of NSCLC were adenocarcinoma (ADC) with 267 cases (68.3%) and squamous cell carcinoma (SqCC) with 87 cases (22.3%). Among smokers, 66.6% were diagnosed with ADC and 24.6% with SqCC; among never smokers (n = 63), 84.1% had ADC and 9.5% SqCC. Clinical staging (CS) at diagnosis was IV in 251 cases (81.6%) and locally advanced (stage IIIB) in 62 cases (18.4%). From patients diagnosed with ADC, only 52.1% (n = 139) have been tested for EGFR mutation and, of these, 21.6% (n = 30) had an EGFR activating mutation. Only 43.3% (n = 13) of those with EGFRm (n=30) received an EGFR-TKI as initial therapy, while the remaining were treated with cytotoxic chemotherapy. Based on the number of patients with EGFRm, the rate of access of EGFR-TKIs in first-line treatment was 75% in private care, compared to 31.8% in public care. Only 8 of 13 mutated patients (61.5%) treated with EGFR-TKI were evaluable for response, and the disease control rate was 62.5%.
8eea62084ca7e541d918e823422bd82e Conclusion
The frequency of EGFRm in locally advanced or metastatic ADC in Brazil was comparable to previous studies. Access to EGFR test and EGFR-targeted therapies are restricted specially in public health system. In Brazil, public policies to assure a broader access to these technologies must be implemented.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.16-02 - Phase III Study of Canakinumab (ACZ885) as Adjuvant Therapy in Patients with Surgically Resected NSCLC (ID 12069)
12:00 - 13:30 | Author(s): Pedro De Marchi
- Abstract
Background
Preclinical and clinical data suggest that cytokines such as interleukin (IL)-1β can promote angiogenesis and tumor growth, and are essential to tumor invasiveness. Canakinumab (ACZ885) is a high-affinity human IgGκ anti-IL-1β monoclonal antibody approved for patients with various IL-1–driven auto-inflammatory diseases. In the Phase III Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) in patients with atherosclerosis, canakinumab was associated with a significant reduction in the incidence of fatal and non-fatal lung cancer in patients with increased high-sensitivity C-reactive protein levels. ACZ885T2301 (NCT03447769) is evaluating the efficacy and safety of adjuvant canakinumab versus placebo in patients with surgically resected non-small cell lung cancer (NSCLC).
a9ded1e5ce5d75814730bb4caaf49419 Method
This Phase III, randomized, double-blind, placebo-controlled study is enrolling patients (≥18 years, Eastern Cooperative Oncology Group Performance Status ≤1) with completely resected (R0) American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) v.8 stages II−IIIA and IIIB (T >5 cm and N2) NSCLC, who have completed standard-of-care adjuvant treatments, including cisplatin-based chemotherapy and mediastinal radiation therapy (if applicable). Prior treatment with neoadjuvant chemotherapy or radiotherapy is not permitted. Approximately 1500 patients will be randomized 1:1 to receive canakinumab (200 mg every 3 weeks [Q3W], subcutaneous [s.c.]) or placebo (Q3W, s.c.) on Day 1 of 21-day cycles for 18 cycles or until disease recurrence, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, death, or loss to follow-up. Following baseline screening, imaging assessment will be performed every 12 weeks for the first year (treatment phase) following Cycle 1 Day 1, then every 26 weeks during Years 2 and 3, and annually during Years 4 and 5 (post-treatment surveillance phase). Randomization will be stratified by AJCC/UICC v.8 stage, tumor histology, and region.
The primary objective is to compare disease-free survival (DFS) in the canakinumab versus placebo arms, as determined by local investigator assessment. Secondary objectives include a comparison of the two treatment groups with respect to overall survival (key secondary objective), lung cancer-specific survival, safety, pharmacokinetics and immunogenicity of canakinumab, and patient-reported outcomes. Exploratory objectives include assessment of the relationship between pharmacokinetics, pharmacodynamics, safety, and efficacy, and evaluation of correlation between cytokines/soluble markers and efficacy endpoints. Enrollment is ongoing.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable
8eea62084ca7e541d918e823422bd82e Conclusion
Section not applicable
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