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Nir Peled
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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 | Presenting Author(s): Nir Peled
- 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.
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P87 - Targeted Therapy - Clinically Focused - RET (ID 264)
- 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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P87.01 - Higher Dose Alectinib for Advanced RET+ NSCLC: Results from the RET+ Cohort of the Blood First Assay Screening Trial (BFAST) (ID 1579)
00:00 - 00:00 | Presenting Author(s): Nir Peled
- Abstract
Introduction
BFAST (NCT03178552) is an ongoing multicentre, open-label, multi-cohort study investigating the activity of targeted therapies or immunotherapy in patients with treatment-naïve advanced NSCLC according to genomic features of cell-free DNA detected by blood-based next-generation sequencing. Half-maximal inhibitory concentration of alectinib for RET kinase appears to be higher than that for anaplastic lymphoma kinase (ALK), suggesting the need to explore a higher dose than the currently approved 600mg BID for ALK+ NSCLC. The RET+ cohort followed a single-arm, open-label, non-randomised design, comprising a phase I dose escalation followed by a phase II dose expansion. Enrolment into the RET+ cohort was closed following the phase I dose escalation, and the phase II portion was not initiated. Phase I results are presented (data cut-off: 27 February 2019).
Methods
Patients aged ≥18 years with treatment-naïve stage IIIB/IV RET+ NSCLC received alectinib 900mg BID, with possible dose escalation to 1,200mg BID. The primary endpoint of this cohort was investigator (INV)-assessed confirmed objective response rate (ORR; indicated by two objective response assessments based on RECIST v1.1, separated by ≥4 weeks). Secondary endpoints included efficacy (Independent Review Facility [IRF]-assessed confirmed ORR; INV- and IRF-assessed duration of response, clinical benefit rate and survival), PK parameters and safety (dose-limiting toxicity [DLT] and adverse events [AEs]).
Results
Eight patients (mean age 59 years; [range: 40–70]) received alectinib in the dose-escalation portion. All patients had stage IV adenocarcinoma, with CNS metastases present at baseline in five patients. The confirmed best overall response was stable disease in four patients and progressive disease (PD) in one patient. Three patients died before their first tumour assessment; four patients died in total (reasons for death: rapid clinical progression, worsening dyspnoea/respiratory failure due to NSCLC, unknown death at home, unknown death after PD in long-term follow up; n=1 each [12.5%]). All deaths occurred during the study or follow-up. Due to the limited number of patients with a full, evaluable PK profile (54 samples from eight patients), no formal PK analysis was performed. Clinical courses and the genomic landscape will be further assessed. At data cut-off, the mean treatment duration was 3.9 months (range: 0–8). All patients reported ≥1 AE. Six patients (75.0%) experienced treatment-related AEs. The most common AEs were: constipation (n=5 [62.5%]), dyspnoea (n=4 [50.0%]), fatigue and headache (n=3 each [37.5%]). Seven patients (87.5%) experienced grade ≥3 AEs; none was experienced by more than one patient. Serious AEs were reported by five (62.5%) patients. AEs leading to withdrawal or dose modification/interruption of study treatment occurred in three (37.5%) and four patients (50.0%), respectively. One DLT (unexplained death) was reported in six DLT-evaluable patients.
Conclusion
Enrolment to the phase I dose escalation was closed prematurely and the phase II dose expansion was not initiated at the discretion of the sponsor. Due to the low rate of DLTs seen in patients treated with alectinib 900mg BID, escalation to 1,200mg BID could have occurred if the study continued. Due to the nature of this study, limited efficacy, safety and PK data were collected.
