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Saadettin Kilickap
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OA01 - Established Drugs in Special Populations and New Drugs in Established Populations (ID 226)
- Event: WCLC 2020
- Type: Oral
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 09:15 - 10:15, Scientific Program Auditorium
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OA01.03 - Clinical Benefits of First-Line (1L) Cemiplimab Monotherapy by PD-L1 Expression Levels in Patients With Advanced NSCLC (ID 3035)
09:15 - 10:15 | Presenting Author(s): Saadettin Kilickap
- Abstract
- Presentation
Introduction
Despite approval of programmed cell death (PD)-1 inhibitor monotherapy as 1L treatment for advanced non-small cell lung cancer (NSCLC), the clinical significance of PD-ligand 1 (PD-L1) expression levels above the 50% threshold remains unclear.
Methods
EMPOWER-Lung 1 is a randomized, open-label, Phase 3 study of anti–PD-1 cemiplimab 350 mg every 3 weeks, versus platinum doublet chemotherapy, as 1L treatment in patients with advanced NSCLC and PD-L1 ≥50% (NCT03088540). This exploratory post-hoc analysis assesses the clinical benefits of study treatment by PD-L1 expression tertiles in a randomized sub-population (n=475) with PD-L1 ≥50% by 22C3 assay. Data cut-off was March 1, 2020.
Results
In the cemiplimab arm (n=238), 33.6%, 31.9%, and 34.5% of patients had PD-L1 ≥90%, >60% to <90%, and ≥50% to ≤60%, respectively; corresponding proportions in the chemotherapy arm (n=237) were 34.2%, 30.4%, and 35.4%, respectively. Overall, cemiplimab provided significantly better OS, PFS, and objective response rate (ORR) than chemotherapy, with incremental benefits by increasing PD‑L1 expression seen with cemiplimab, but not chemotherapy (Table). The largest difference in ORR between cemiplimab (38.8% [95% CI: 28.1–50.3]) and chemotherapy (14.8% [95% CI: 7.9–24.4]) was observed in patients with PD-L1 ≥90%. Depth of tumor size reduction was greater with cemiplimab than that of chemotherapy and correlated with PD-L1 levels (Figure). Median DOR has not been reached with cemiplimab (95% CI: 10.5–not evaluable) versus chemotherapy (6-months [95% CI: 4.3–8.3]). Kaplan–Meier estimated DOR >12 months was higher with cemiplimab (67.7% [95% CI: 45.7–82.3]) compared to chemotherapy (15.0% [95% CI: 1.5–42.6]).
Conclusion
Overall, the benefit (OS, PFS, and ORR) with cemiplimab was superior to chemotherapy, and incrementally associated with PD-L1 expression levels. Thus, baseline PD-L1 expression levels may be used to identify patients with advanced NSCLC who are most likely to derive greatest benefit from 1L cemiplimab monotherapy.
Table. Correlation of survival and objective response rate with baseline PD-L1 levels Overall survival Progression-free survival Tumor response Median, months
(95% CI)HR (95% CI) Median, months
(95% CI)HR (95% CI) ORR, % (95% CI) Overall NR (NE–NE)
vs.
12.1 (10.2–17.5)0.57
(0.40–0.80)6.3 (4.5–8.5)
vs.
5.6 (4.3–6.2)0.60
(0.47–0.77)35.3 (29.2–41.7)
vs.
17.7 (13.1–23.2)By PD-L1 expression tertile PD-L1 ≥90% NR (13.4–NE)
vs.
13.3 (10.2–NE)0.54
(0.27–1.10)12.7 (9.8–13.4)
vs.
6.1 (4.2–6.2)0.33
(0.19–0.58)38.8 (28.1–50.3)
vs.
14.8 (7.9–24.4)PD-L1 >60 to <90% NR (NE–NE)
vs.
14.2 (9.6–17.5)0.49
(0.26–0.92)6.2 (4.2–8.4)
vs.
4.3 (4.1–5.9)0.57
(0.38–0.85)39.5 (28.4–51.4)
vs.
16.7 (8.9–27.3)PD-L1 ≥50 to ≤60% NR (13.2–NE)
vs.
11.7 (8.3–NE)0.74
(0.44–1.24)4.3 (2.8–5.2)
vs.
6.0 (4.4–6.2)0.89
(0.61–1.29)28.0 (18.7–39.1)
vs.
21.4 (13.2–31.7)Median survival, and ORR data are shown for cemiplimab versus chemotherapy, respectively. ORR defined as the proportion of patients with a best overall response of confirmed complete or partial response. PFS in the PD-L1 ≥50 to ≤60% subgroup has the widest CIs which makes the PFS estimate HR highly unstable.
CI, confidence interval; HR, hazard ratio; NE, not evaluable; NR, not reached; ORR, objective response rate; PD-L1, programmed cell death-ligand 1; PFS, progression free survival.
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P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P84.03 - GLASS: Global Lorlatinib for ALK(+) and ROS1(+) Retrospective Study: Real World Data of 123 NSCLC Patients (ID 3172)
00:00 - 00:00 | Author(s): Saadettin Kilickap
- Abstract
Introduction
Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib.
Methods
This is an international, multicenter, retrospective study, which aimed to describe the efficacy and safety of lorlatinib in previously treated ALK/ROS1(+) NSCLC. All patients were treated through an early access program, when no other targeted therapy was available.123 patients were enrolled retrospectively (data cut-off 1/1/2019). Outcome and response were defined by each investigator upon RECIST 1.1 criteria.
Results
From March 2015 to January 2019, 106 ALK(+) and 17 ROS1(+) patients were recruited from 8 different countries. The ALK(+) cohort included 50% males, 73% never-smokers and 68% with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60% and 62%, with disease control rates (DCR) of 91% and 88% respectively. Mean duration of therapy (DoT) was 23.9±1.6 months and median overall survival (mOS) was 89.1±19.6 months. ROS1 cohort enrolled 53% males, 65% never-smokers and 65% had brain metastases. EC and IC RR were 62% and 67% with DCR of 92% and 78% respectively. Median DoT was 18.1±2.5 months and mOS of 90.3±24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters.
The most common adverse events of any grade were peripheral edema (48%), hyperlipidemia (47%), weight gain (25%) and fatigue (30%). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18% of patients.
Conclusion
Lorlatinib shows outstanding extracranial and intracranial efficacy in ALK or ROS1(+) NSCLC. The observed mOS of 89±19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90±24 months is unprecedented for ROS1(+) NSCLC.
