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Fabio Andre Franke



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    OA05 - Clinical Trials in IO (ID 899)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 106
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      OA05.06 - CheckMate 227: Patient-Reported Outcomes of First-Line Nivolumab + Ipilimumab in High Tumor Mutational Burden Advanced NSCLC (ID 13450)

      14:25 - 14:35  |  Author(s): Fabio Andre Franke

      • Abstract
      • Presentation
      • Slides

      Background

      The randomized, open-label, multipart phase 3 study CheckMate 227 (NCT02477826) demonstrated a significant progression-free survival benefit (co-primary endpoint) with first-line nivolumab+ipilimumab versus histology-based, platinum-doublet chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and high tumor mutational burden (TMB; ≥10 mutations/Mb). Patient-reported outcomes (PROs) for this population within CheckMate 227 are presented.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eligible chemotherapy-naïve patients had stage IV or recurrent NSCLC, ECOG performance status 0−1, and no known sensitizing EGFR/ALK alterations. PROs were assessed as an exploratory endpoint; this analysis included patients with high TMB randomized to nivolumab+ipilimumab or chemotherapy; specific outcomes included proportion of patients with disease-related symptom deterioration by 12 weeks and time to deterioration in symptoms (by Lung Cancer Symptom Scale [LCSS] Average Symptom Burden Index [ASBI]), and assessment of quality of life and overall health status (by EuroQoL-5 Dimension [EQ-5D] utility index [UI] and visual analog scale [VAS]). PROs were evaluated each cycle (Q2W, nivolumab+ipilimumab; Q3W, chemotherapy) for the first 6 months, every 6 weeks thereafter during treatment, and at follow-up visits 1/2. EQ-5D was also assessed during survival follow-up.

      4c3880bb027f159e801041b1021e88e8 Result

      PRO completion rates were ~90% at baseline and >80% for nearly all on-treatment assessments. Among patients with high TMB, fewer patients in the nivolumab+ipilimumab (n=139) versus chemotherapy (n=160) groups reported symptom deterioration by week 12, irrespective of whether they were still on therapy or had discontinued (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% CI: 2.4–22.5]). Time to first deterioration (TTD) using common assessment time points (on/off treatment) was delayed with nivolumab+ipilimumab versus chemotherapy for the LCSS ASBI (hazard ratio [HR]: 0.40; 95% CI: 0.26–0.63) and 3-Item Global Index (3-IGI; HR: 0.56; 95% CI: 0.38–0.82). The estimated benefit in TTD generally favored nivolumab+ipilimumab for individual symptoms in the ASBI and each item in the 3-IGI (HRs: 0.48–0.74), except for hemoptysis (HR: 1.20), which exhibited very low burden; an advantage for nivolumab+ipilimumab was also seen in the EQ-5D VAS (HR: 0.62; 95% CI: 0.42–0.92) and UI (HR: 0.50; 95% CI: 0.34–0.73). Mean changes from baseline with nivolumab+ipilimumab showed early and clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; for patients treated with chemotherapy, symptoms and quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following completion of chemotherapy (EQ-5D VAS).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Nivolumab+ipilimumab demonstrated early and sustained improvements in health-related quality of life versus chemotherapy in patients with advanced NSCLC and high TMB.

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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): Fabio Andre Franke

      • Abstract
      • Slides

      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): Fabio Andre Franke

      • Abstract
      • Slides

      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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