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Frank Griesinger
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-28 - Impact of Afatinib Dosing on Safety and Efficacy Real-World in Patients with EGFR Mutation-Positive Advanced NSCLC (ID 13276)
16:45 - 18:00 | Author(s): Frank Griesinger
- Abstract
Background
Tolerability-guided dose adjustment of afatinib reduced incidence and severity of adverse drug reactions (ADRs) without affecting efficacy in the LUX-Lung (LL) studies in patients with EGFR mutation-positive (EGFRm+) NSCLC. We evaluated the impact of modifying the recommended starting dose of afatinib (40mg) on efficacy and safety in a real-world setting.
a9ded1e5ce5d75814730bb4caaf49419 Method
This non-interventional, observational, multi-country/site study used medical records of TKI-naïve patients with EGFRm+ (Del19/L858R) NSCLC treated with first-line afatinib. Primary outcomes were % patients with ADRs by severity, time on treatment (TT), and time to progression (TTP), relative to LL3. Secondary outcomes were % of patients with/reasons for modified starting dose.
4c3880bb027f159e801041b1021e88e8 Result
228 patients from 13 countries were included. Baseline characteristics were generally similar to LL3, but with more Del19 patients (78% vs 49%) and fewer Asian patients (44% vs 72%); 12% had ECOG PS 2–3. 31% of patients received an afatinib starting dose of <40 mg; 20% of patients starting with <40 mg increased their dose during the study. 67% of 40 mg starters underwent dose reductions, with 86% of those occurring in the first 6 months. Dose reductions were more frequent in females, Eastern Asian patients, and those with lower body weight. The main reason for dose modification was ADRs. In <40 mg starters, overall ADR incidence was similar to that in ≥40 mg starters, with fewer G3 (17% vs 25%) and no G4 ADRs. There were no new safety signals, and fewer ≥G3 ADRs and serious adverse events (SAEs) than in LL3 (28% vs 49% and 5% vs 14%, respectively). >60% of patients received medications to treat diarrhea and manage skin AEs. Median TT and TTP were 18.7 months and 20.8 months, respectively, and were not impacted by reduced starting dose or dose modification (19.4/17.7/19.5 and 25.9/20.0/29.0 months for patients who started on ≤30 mg/reduced to <40 mg/remained on ≥40 mg, respectively). The efficacy of afatinib was demonstrated across all patient subgroups analysed (ECOG PS 0/1 vs 2/3, age <75 yrs vs ≥75 yrs, EGFR mutational status); TT and TTP were significantly longer in patients with ECOG PS0/1 versus PS2/3.
8eea62084ca7e541d918e823422bd82e Conclusion
As in pivotal trials, dose adjustments with afatinib in real-world practice reduced the frequency and intensity of ADRs without impacting efficacy. RealGido demonstrated long TT/TTP regardless of afatinib dose adjustment or reduced starting dose, and an acceptable safety profile. The results highlight the benefit of tailoring afatinib dose based on individual patient characteristics and ADRs to optimize outcomes.
6f8b794f3246b0c1e1780bb4d4d5dc53
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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): Frank Griesinger
- 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
6f8b794f3246b0c1e1780bb4d4d5dc53
