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Mor Moskovitz
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P50 - Small Cell Lung Cancer/NET - Real World Outcomes (ID 232)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P50.04 - Real-World Survival Outcomes with Immune Checkpoint Inhibitors in Large Cell Neuroendocrine Tumors of Lung. (ID 1949)
00:00 - 00:00 | Author(s): Mor Moskovitz
- Abstract
Introduction
While immune checkpoint inhibitors (ICI) have emerged as standard of care for most patients with advanced lung cancer, little is known regarding their efficacy in patients with advanced large cell neuroendocrine tumors of lung (aLCNEC). We sought to report real-world outcomes in this population.
Methods
125 consecutive patients with aLCNET were identified in the electronic databases of 4 participating cancer centers. Tumors were classified as small-cell lung cancer (SCLC)-like (TP53+RB1 co-mutations or loss), non-small-cell lung cancer (NSCLC)-like (lack of TP53/RB1 alterations), or molecular subtype unknown. Overall survival (OS) since advanced disease diagnosis (OS DX) and OS since ICI initiation (OS ICI) were captured.
Results
Among 125 patients with aLCNEC, 7 were SCLC-like, 15 were NSCLC-like and 103 were unknown; 41 patients received ICI (Group A) and 84 did not receive ICI (Group B). With median follow-up of 11.8 months (mo) [IQR, 7.5-17.9] and 6.0 mo [IQR, 3.1-10.9], 66% and 76% of patients died in groups A and B, respectively. Median OS DX was 12.4 mo (95% CI, 10.7-23.4) and 6.0 mo (95% CI, 4.7-9.4) in groups A and B, respectively (p-0.02) (Figure A). HR for OS DX was 0.59 (95% CI, 0.38-0.93 - unadjusted) and 0.55 (95% CI, 0.33-0.92 - adjusted for age, ECOG PS and presence of liver metastases) (Figure B). OS ICI for patients receiving ICI as monotherapy (n=36) was 11.0 mo (6.1-19.4). In the univariate analysis, ECOG PS at ICI initiation (ECOG PS 0/1 vs 2-4; HR-0.38; 95% CI, 0.15-0.95) and presence of liver metastases (HR-3.04; 95% CI, 1.33-6.96) significantly correlated with OS ICI. Patients with NSCLC-like aLCNEC had numerically worse outcomes with ICI (Table).
Table.
Group
OS DX
median (95% CI), mo
p value
HR (adjusted for age, ECOG PS, liver metastases)
(95% CI)
OS ICI
median (95% CI), mo
A (ICI, n=41)
12.4 (10.7-23.4)
0.02
0.55 (0.33-0.92)
B (no ICI, n=84)
6.0 (4.7-9.4)
A (ICI, NSCLC-like, n=10)
11.6 (10.6-NR)
0.63
B (no ICI, NSCLC-like, n=5)
18.6 (16.9-NR)
A (ICI as monotherapy, n=36)
11.0 (6.1-19.4)
A (ICI as monotherapy, NSCLC-like, n=9)
9.3 (6.1-NR)
Figure.
Conclusion
In aLCNEC, ICI had a positive impact on OS. Prospective research is needed to validate these results and to correlate the benefit with the tumor molecular subtype.
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P78 - Immunotherapy (Phase II/III Trials) - Immune Checkpoint Inhibitor Single Agent (ID 255)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P78.07 - High Grade Toxicity and Response to PD-1 Axis Inhibitors in Advanced NSCLC (ID 3499)
00:00 - 00:00 | Presenting Author(s): Mor Moskovitz
- Abstract
Introduction
Immunotherapy with PD-axis inhibitors has become an integral part of treatment of advanced Non Small Cell Lung Cancer (aNSCLC) in the first or second lines of therapy, as single agent or combined with chemotherapy. Immune-related adverse events (irAE) has been observed with PD-1 axis inhibitors at various degrees of severity, while high-grade toxicity (grade 3-4 according to Common Terminology Criteria for Adverse Events; CTCAE) require cessation of therapy. Nevertheless, several studies indicated improved prognosis in patients with irAE.
Methods
In this retrospective study, we identified consecutive aNSCLC patients, treated with PD-1 axis inhibitors as single agent (Pembrolizumab, nivolumab, atezolizumab) in the first or second line at Rambam Hospital, Israel; Clinical and demografic data was extracted from the electronic patient records, including survival and toxicity data. Patients who had to stop treatment with PD-1 axis inhibitors due to toxicity were considered to have high-grade toxicity, corresponding with grade 3-4 toxicity according to CTCAE. We assessed the survival and response of patient with high grade toxicity to PD-1 axis inhibitos (group A) to patient treated with PD-1 axis inhibitor with no high-grade toxicity (group B). Overall survival (OS) Survival was assessed from diagnosis of metastatic disease.
Results
One hundred and sixty-three patients with aNSCLC were treated with PD-1 axis inhibitors as single agent between January 2016 to December 2019 at the Rambam hospital oncology institute; Median age was 65 years (range 40 to 91 years); 119 men (74%); 80% past or present smokers; 114 (76%) patients had adenocarcinoma histology and 36 (24%) patients had squamous cell carcinoma;
Brain or liver metastases were found in 29 patients (18.5%); 118 patients (73%) deceased at the time of data cutoff.
While on treatment with PD-1 axis innhibitors, 32 patients (19%) discontinued treatment due to high-grade toxicity (group A), and 121 patients (81%) did not discontinue treatment due to toxicity (group B).
The high grade side effects that mainly resulted in discontinuation were colitis (10% of all patient), pneumonitis (4%), hepatitis (3%) and nephritis (2%).On univariate analysis, age, smoking, histology of cancer and weight loss were not correlated to discontinuation of treatment.
The median survival of group A was 30 months( 95% CI:8.14-53.05), vs. 23 months for group B (95% CI: 16.77-29.42; p= 0.051).
Conclusion
On this retrospective real-world study of aNSCLC patients treated with PD-1 axis inhibitors as single agent therapy, patients who suffered high grade irAE and had to stop therapy due to the toxicity, had significantly higher OS compared to the cohort of patients with no high gade toxicity requiring treatment cessation. .
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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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P84.10 - The Impact of 3rd-Line ALK Inhibitors in ALK Positive NSCLC in Real-World Data (ID 3662)
00:00 - 00:00 | Presenting Author(s): Mor Moskovitz
- Abstract
Introduction
ALK inhibitors (ALKi) are the standard treatment for metastatic ALK-rearranged Non-Small Cell Lung Cancer (NSCLC) patients in the first and second line setting. We conducted a real-world multi-institutional study, aiming to compare third-line ALKi versus chemotherapy in these patients.
Methods
Consecutive ALK-positive advanced NSCLC patients, treated with at least one ALKi were identified in the working databases of seven Israeli oncology centers (the full cohort). Demographic and clinical data was collected. Patients receiving any systemic treatment beyond 2 ALKi comprised the third-line cohort, whether a third ALKi (Group A) or chemotherapy (Group B). Groups were compared in terms of overall survival (OS) and time-to-next-treatment line (TNT).
Results
For the full cohort (n=170), with a median follow up of 41 months, median OS (mOS) was 52 months (95% CI: 32-65). Age (HR 1.02, 95% CI: 1.01-1.04, p=0.009) and the number of ALKi (HR 0.765; 95% CI: 0.61-0.95; P=0.024) were significantly correlated with OS. The third-line cohort included 40 patients; 27 - group A, 13 - group B. The mOS of the third-line cohort from the onset of third line was 27 months in group A (95% CI: 13-NR), and 13 months for group B (95% CI: 3-NR; p=0.12). Chemotherapy as first line (HR 0.17, 95% CI: 0.05-0.52, p=0.002) and a higher number of ALKi (HR 0.38, 95%CI: 0.20-0.86, p=0.011) correlated significantly with OS of the third-line cohort. TNT was 9 months for group A (95% CI: 5-19) and 3 months for group B (95% CI: 0-NR, p=0.085).
Conclusion
We report mature real-world data of more than 4 year median OS in ALK-positive patients. First-line chemotherapy for these patients was associated with better outcome, suggesting further studies are required of such an approach. OS and TNT demonstrated a statistically non-significant trend for better outcome in patients receiving a third-line ALKi.
