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Jens Benn Sørensen
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EP1.08 - Oligometastatic NSCLC (ID 198)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Oligometastatic NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.08-07 - Correlation Between Genetic Profiling and Response in Danish ALK-Positive NSCLC Patients Treated with Crizotinib (Now Available) (ID 923)
08:00 - 18:00 | Author(s): Jens Benn Sørensen
- Abstract
Background
In 2011 Crizotinib received FDA approval for the treatment of ALK-positive NSCLC. Due to large diversity in clinical course of these patients, baseline genomic profiling at diagnostic biopsy was performed to find possible correlations with clinical features.
Method
We performed a retrospective analysis of 28 consecutive patients receiving Crizotinib for metastatic, immunohistochemistry (IHC)- and fluorescens in-situ hybridization (FISH)-determined ALK-positive NSCLC, between September 2011 and DATE. Clinical data were collected by chart review. DNA/RNA genomic profile were performed using the patients’ biopsy at the time of diagnosis or at initiation of therapy using targeted next-generation sequencing (NGS) Oncomine™ Focus (ThermoFisher Scientific) and Archer® Solid Tumor (ArcherDx) assays. Baseline clinical features and genetic information were correlated with overall survival and progression free survival.
Result
The cohort included 15 women and 13 men, median age 56 (range 22-83). Median PFS was 5.2 months (CI 2.9-9.5), median OS was 17.3 months (CI 8.8-33.2). Favorable prognostic factors for both PFS and OS were PS 0-1 vs 2 (n=25), male gender (n=13), never smoking (n=18) and up-front brain metastasis (n=6). Fourteen patients were treated with Crizotinib as 2nd line therapy and had better OS, but similar PFS. Crizotinib-responders (CR+PR+SD) represented 71% and -no responders (PD) 29%. Most patients received further treatment after progression on Crizotinib (68%). The most common ALK-fusion-partner was EML4 (64%; of which 50% were variant v1, 28% v2, 22% v3). For 8 patients (28%) no fusion partner was identified. In 7 cases (25%) the FISH-detected ALK-rearrangement was not confirmed by IHC and NGS and 4 of them did not respond, 1 case (4%) was FISH-/IHC-positive but NGS-negative and responded. Four of 8 non-responders (all 4 IHC-negative, 3 NGS-negative) showed another de novo gene-alteration (in KRAS, ALK or EGFR). Two patients with another fusion-partner: KIF5B(17)-ALK(20) and TEMP3(6)-ALK(20) had an aggressive clinical course after short-term response. In contrast, a patient with pre-existing ALK-mutations F1174L and R1275Q, had the longest duration of treatment with Crizotinib (2.5 years). Patients with EML4 fusion-partner (n=18) were prone to achieve better OS than the others. Rebiopsies at progression for 8 patients showed different TKI-resistance mechanisms.
Conclusion
ALK-positive NSCLC represents a heterogenous disease, which in most cases can be encapsulated by ALK-TKI. Although this small cohort does not allow to draw unambiguous conclusions, it does indicate that the efficacy of treatment may vary with different ALK-fusion-partners. Moreover, ALK-positive NSCLC should be validated and classified by NGS-testing at baseline to optimize the choice of ALK- TKI.
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-51 - Treatment with Immune Checkpoint Inhibitors for Advanced NSCLC in Elderly and Frail Patients. A Real-Life Experience (Now Available) (ID 1327)
09:45 - 18:00 | Author(s): Jens Benn Sørensen
- Abstract
Background
Immune checkpoint inhibitors (ICIs) has changed the standard treatment in advanced stage non-small cell lung cancer (NSCLC). However, patients above 75 years and patients in performance status (PS) 2 are underrepresented in randomized clinical trials. Hence, the efficacy and safety of treatment in these large subgroups of patients remains unclear. We report a real-life study of such patients treated with immunotherapy in a second-line setting.
Method
Data from consecutive patients with advanced NSCLC who had 2nd line treatment with ICIs at the University Hospitals in Copenhagen during November 2015 to March 2019 were obtained from medical records. Treatment efficacy and safety was evaluated, and treatment related adverse events (AEs) were registered.
Result
A total of 224 NSCLC patients were treated with either nivolumab or pembrolizumab: The median follow up time of was 12.3 months. The median progression free survival (PFS) was 4.9 months, and median overall survival (OS) was 12.9 months CI [9.7-14.6]. The median age was 67.7 years, while 45 patients (20%) were 75 years or older. There were no significant difference when comparing patients ≥ 75 years vs. < 75 years with respect to PFS ( 5.3 vs. 4.9 months, p = 0.81) nor in OS (14.2 vs. 12.8 months, p = 0.93). PFS and OS were correlated with PS: The PFS was 7.7, 4.7 and 2.0 months (p = 0.0003) in PS 0, PS 1 and PS 2, respectively. OS was 20.9, 12.0 and 3.0 months (p > 0.0001) in PS0, PS1 and PS 2, respectively. AEs were reported in 183 patients (82%), among whom 44 patients (20%) experienced grade 3-5. There were no difference in AEs in younger patients compared to older ≥ 75 years (p = 0.18). The incidence of grade 3-5 AEs was significantly higher among patients in PS 2 (35%) compared to PS 0-1 (17%), (p < 0.001).
Conclusion
NSCLC patients ≥ 75 years had efficacy and safety profiles in second-line ICIs comparable to those of younger patients. However, treatment with ICIs in patients with PS 2 was associated with a significant lower PFS and OS. The high risk of seriously AEs in patients with PS 2 is of concern and warrants further investigation.
