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Gilberto Schwartsmann
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P2.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 961)
- 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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P2.12-04 - Liposomal Irinotecan vs Topotecan in Patients with Small Cell Lung Cancer Who Have Progressed On/After Platinum-Based Therapy (ID 12768)
16:45 - 18:00 | Author(s): Gilberto Schwartsmann
- Abstract
Background
Small Cell Lung Cancer (SCLC) accounts for ~15% of all lung cancers; it is an aggressive disease marked by rapid growth and early metastasis. Patients typically demonstrate initial sensitivity to chemotherapy and radiotherapy, followed by rapid relapse and development of drug resistance. Topotecan, a topoisomerase I (TOP1) inhibitor, is the only agent approved for second-line treatment in the United States and Europe. Liposomal irinotecan (nal-IRI) has demonstrated sustained TOP1 inhibition, with liposomal deposition in tumor tissue through leaky vasculature, followed by irinotecan release and subsequent conversion to the active metabolite SN-38. Pre-clinical data suggests that nal-IRI has improved anti-tumor activity compared to topotecan. The current trial (NCT03088813) is being undertaken to investigate the safety and efficacy of nal-IRI versus intravenous topotecan in patients with SCLC who have progressed on or after platinum-based first-line therapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
There are two parts of this study: Part 1 is an open-label, single-arm, safety run-in phase and Part 2 is a randomized, controlled, efficacy assessment phase. Key inclusion criteria include ECOG performance status of 0–1, adequate organ function, histopathologically/cytologically confirmed SCLC, evaluable disease (RECIST v1.1), and life expectancy ≥12 weeks. Prior exposure of immuno-oncology therapies is allowed. Key exclusion criteria include a diagnosis of large cell neuroendocrine lung carcinoma, prior treatment regimens with TOP1 inhibitors, and retreatment with the same platinum-based regimen after relapse of first-line therapy. In Part 1, patients will be treated with different doses of nal-IRI to identify a tolerable dose level; this dose level will be expanded to include a total of 24 patients. The primary endpoint is safety and tolerability, with secondary endpoints including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
In Part 2, ~450 patients will be randomized in a 1:1 ratio between nal-IRI and IV topotecan. The primary endpoint is OS, followed by PFS, ORR, patient-reported outcomes, and exploratory analyses. Patients will be treated for a minimum of 3 cycles (1 cycle = 6 weeks) or until progressive disease or unacceptable toxicity. Safety analyses will be performed using the safety population, defined as all patients receiving any study drug.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable - Trial in progress
8eea62084ca7e541d918e823422bd82e Conclusion
Section not applicable - Trial in progress
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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): Gilberto Schwartsmann
- 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.
6f8b794f3246b0c1e1780bb4d4d5dc53
