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Dwight H Owen
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P09 - Health Services Research/Health Economics - Real World Outcomes (ID 121)
- Event: WCLC 2020
- Type: Posters
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P09.13 - Bone Metastases and Overall Survival in Patients with Metastatic Non-Small Cell Lung Cancer Treated with Pembrolizumab (ID 3124)
00:00 - 00:00 | Author(s): Dwight H Owen
- Abstract
Introduction
Bone metastases (BM) and skeletal-related events (SRE) are a common cause of morbidity in patients with metastatic non-small cell lung cancer (mNSCLC). Data on the impact of BM on overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI) is limited. Here we report the incidence, impact on survival, and risk factors for SRE in patients with mNSCLC treated with first-line pembrolizumab monotherapy or pembrolizumab plus chemotherapy.
Methods
We conducted a retrospective study of patients with mNSCLC treated with first-line pembrolizumab or pembrolizumab plus chemotherapy at our institution from 2017-2020. The associations between SRE and categorical variables were studied using Fisher’s exact test and with continuous variables using the Kruskal-Wallis test. Kaplan-Meier plots were used to visualize survival curves. The association between baseline BM and OS was examined using a Cox proportional hazard model. OS was calculated from date of ICI initiation to death from any cause or last follow-up.
Results
We identified a cohort of 202 patients: 93 (46%) treated with pembrolizumab and 109 (54%) treated with pembrolizumab plus chemotherapy; 39 (19%) had squamous histology and 163 (81%) had nonsquamous histology; median age 62.7; median OS 33.7 months (95% CI: 17.2 – NR). In our cohort, 87 (43%) patients had BM at time of ICI initiation and 47 (23%) developed SRE after ICI initiation. Patients who developed SRE were more likely to have baseline BM than those without SRE (91.5% vs 28.4%, p<0.001). Development of BM during treatment with ICI and performance status were also significantly associated with SRE (p<0.001 and p=0.006, respectively). Patients with BM at time of ICI, or development of new or progression of existing BM while on ICI, had shorter survival than those without (Figure 1a and Figure 1b, respectively). In multivariate survival analysis, the hazard of death for patients with baseline BM was 2.85 times those without (HR=2.85, 95% CI: 1.53, 5.29, p-value=0.0009) after controlling for age, BMI, performance status, histology, PD-L1 expression, smoking, and SRE. The use of bone-modifying agents (BMA) was not associated with OS, osseous progression, or risk of SRE.
Conclusion
The presence of BM at time of ICI was associated with shorter survival after controlling for multiple clinical characteristics. These patients represent a high-risk cohort for worse outcomes when treated with ICI alone or in combination with chemotherapy. In our cohort BMA were not associated with increased OS or decreased risk of osseous progression or SRE.
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P21 - Locoregional and Oligometastatic Disease - Treatment of Locally Advanced NSCLC (ID 131)
- Event: WCLC 2020
- Type: Posters
- Track: Locoregional and Oligometastatic Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P21.02 - Incidence and Outcomes of Brain Metastases in Unresectable Stage III Patients with NSCLC Treated with Durvalumab after Chemoradiation (ID 2270)
00:00 - 00:00 | Author(s): Dwight H Owen
- Abstract
Introduction
The addition of consolidation durvalumab after concurrent chemo-radiation has demonstrated an improvement in progression-free and overall survival in patients with unresectable stage III NSCLC. In an updated analysis of PACIFIC Study, 6.3% of patients who were treated with durvalumab developed brain metastasis (BMets). We did this study to further evaluate the incidence and treatment of BMets.
Methods
We conducted a retrospective study of patients who received durvalumab for unresectable stage III NSCLC from 2018 to 2019 at our institution after obtaining IRB approval. Clinical and disease characteristics were assessed, including tumor stage, histology, treatment history, BMets history, management and survival. Overall survival (OS) was calculated from the initiation of durvalumab to date of death or censored at last follow-up.
Results
A total of 61 patients were included in this analysis. 25 (40.9%) patients had adenocarcinoma, 27 (44.3 %) patients had squamous cell carcinoma, and 4 (6.6%) patients had adenosquamous. A total of 10 (16.4 %) patients developed BMets after a median of 5.5 months of starting durvalumab and one patient had BMets before receiving durvalumab. Most of patients with BMets were treated with radiation (n=6, 54.5%) and followed by surgery (n=2, 18.1%). Patients with T1 (<3 cm size) tumor have a low incidence of BMets compared to T2-T4 (>3 cm) tumor, p = 0.0132 (Table1). Median survival for patients with BMets and without BMets has not been statistically significant (p = 0.1976) (Figure1).
ConclusionCharacteristic
Level
No Brain Metastasis
(N=50)
Brain Metastasis
(N=11*)
Total
(N=61)
p-value
Age at IO (Years)
Mean (SD)
61.8 (10)
64.6 (7.6)
62.3 (9.6)0.3998
BMI
Mean (SD)
26.7 (6.3)
25.6 (6.7)
26.5 (6.4)0.6027
Race
African American
5 (10.2)
1 (9.1)
6 (10)
0.3857
White, Caucasian
43 (87.8)
9 (81.8)
52 (87)
Other
1 (2)
1 (9.1)
2 (3)
Sex
Male
32 (64)
5 (45)
37 (61)
0.3151
Female
18 (36)
6 (55)
24 (39)
EGFR
Negative
49 (98%)
10 (91%)
59 (97)
0.3306
Positive
1 (2%)
1 (9%)
2 (3)
KRAS
Negative
40 (80)
8 (73)
48 (79)
0.6871
Positive
10 (20)
3 (27)
13 (21)
ALK
Negative
49 (98)
11 (100)
60 (98)
1.0000
Positive
1 (2)
0
1 (2)
T53
Negative
32 (64)
6 (55)
38 (62)
0.7327
Positive
18 (36)
5 (45)
23 (38)
STK11/LKB1
Negative
48 (96)
9 (82)
57 (93)
0.1455
Positive
2 (4)
2 (18)
4 (7)
T stage
T1, Tx
22 (44)
0 (0)
22 (36)
0.0132
T2
7 (14)
3 (27.3)
10 (16)
T3
11 (22)
5 (45.5)
16 (26)
T4
10 (20)
3 (27.3)
21 (21)
N stage
N0, N1
9 (18)
1 (9)
10 (16)
0.7478
N2, N3
5 (10)
2 (18)
7 (11)
PDL1
0%
9 (22)
3 (30)
12 (24)
0.6822
1%+
32 (78)
7 (70)
39 (76)
PDL1
<50%
28 (68)
8 (80)
36 (71)
0.7027
50%+
13 (32)
2 (20)
15 (29)
Table 1: Characteristics of unresectable stage III NSCLC patients treated with durvalumab who developed brain metastasis vs no metastasis
*One patient had brain metastasis before receiving durvalumab
In a cohort of patients treated with consolidation durvalumab for unresectable stage III NSCLC, the incidence of BMets was 16.4%, which is higher than observed in the PACIFIC study. Median OS at 20 months has not been reached for the entire cohort as well as patients with BMets. Further research is needed to better understand the competing risks of BMets in unresectable Stage III NSCLC patients treated with durvalumab.
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P48 - Small Cell Lung Cancer/NET - Chemo - IO (ID 236)
- 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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P48.19 - Outcomes of Patients Treated with First Line Immunotherapy Plus Chemotherapy for ES-SCLC: Real World Outcomes from a Tertiary Academic Center (ID 3385)
00:00 - 00:00 | Author(s): Dwight H Owen
- Abstract
Introduction
The addition of atezolizumab to chemotherapy for first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC) has led to improved median overall survival compared to chemotherapy alone, however no overall survival difference was observed in patients with brain metastases and real world data on outcomes including additional lines of therapy are lacking. We, therefore, conducted an analysis of patients with ES-SCLC treated with first line chemotherapy-atezolizumab evaluating predictors of outcome of patients with brain metastases and patterns of second line therapy.
Methods
We conducted a retrospective study of patients who received first line atezolizumab and chemotherapy for ES-SCLC from 2018 to 2019. Patient clinical and disease characteristics, including baseline demographics, histology, treatment history, location of metastatic sites, and survival were assessed using median and interquartile for the continuous variables and frequencies for the categorical variables. Overall survival was calculated from the initiation of treatment to date of death or censored at last follow-up. The associations between risk factors and OS were examined using Cox proportional hazard models.
Results
We identified 65 patients treated with atezolizumab + chemotherapy: 53(81.5%) patients received atezolizumab maintenance treatment and 12(18.5%) patients did not (10 patients died, 1 patient had progression, 1 patient lost follow up during induction treatment). Overall, 18 (27.7%) patients received additional therapy with 10 patients receiving a total of 2 lines of therapy, 6 patients receiving 3 lines, and 2 patients receiving 4 lines of therapy. Most common additional lines of therapy included chemotherapy (N=9), immune checkpoint inhibitors (N=1), and clinical trial (N=8). Among 15 patients with brain metastases, 10 (66.7%) patients were treated with whole brain radiotherapy, and 5 (33.3%) patients treated with stereotactic radiation. Median overall survival for all patients was 12.3 months (95% CI: 8-15.1months) similar to observed in prior phase 3 studies. In univariate survival analysis, the hazard ratio (HR) of death for patients with liver metastases (N=24) and bone metastases (N=21) were HR=1.66 (95%CI: 0.81-3.41, p=0.16) and HR=1.91 (95%CI: 0.86-4.25, p=0.11) respectively. However, the hazard of death for patients with brain metastases was 82% lower than those without brain metastases (HR:0.18, 95%CI: 0.04-0.75, p=0.018). No significant associations between overall survival with age, performance status, gender, or BMI. (all p-values>0.05)
Conclusion
In this study, median overall survival was just over 1 year for patients with ES-SCLC treated with atezolizumab and chemotherapy for ES-SCLC at a tertiary academic center, consistent with multiple first line phase 3 trials. The low number of patients who received additional lines of therapy demonstrates the importance of improving upfront treatment approaches. Patients with brain metastases had improved overall survival, distinct from prior studies, whereas no overall survival difference was observed for patients with liver or bone metastases.
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P75 - Immunotherapy (Phase II/III Trials) - Misc. Topics (ID 248)
- 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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P75.12 - Prognostic Value of Neutrophil to Lymphocyte Ratio in NSCLC Patients Receiving First Line Immune Checkpoint Inhibitor Therapy (ID 3218)
00:00 - 00:00 | Author(s): Dwight H Owen
- Abstract
Introduction
Despite the introduction of immune checkpoint inhibitor (ICI) therapy, metastatic non-small cell lung cancer (mNSCLC) remains an aggressive and incurable disease. Programed death ligand 1 (PD-L1) expression is currently used to guide first line ICI therapies. Neutrophil to lymphocyte ratio (NLR) has recently been used as an alternative prognostic predictor in advanced cancers. This study evaluated the prognostic value of NLR and PD-L1 expression in patients treated with first line ICI therapy, either pembrolizumab monotherapy or pembrolizumab/carboplatin/pemetrexed for mNSCLC.
Methods
We conducted a retrospective study of patients with Stage IV NSCLC treated with a first line ICI from 2017-2020 at our institution. Baseline NLR was obtained from complete blood count within 7 days of starting treatment and was analyzed as a continuous variable. Tumor PD-L1 expression by immunohistochemistry was performed as standard of care with 22C3 antibody and reported as tumor proportion score (TPS). Median OS (95% CI) was calculated using Kaplan-Meier Survival Estimates. Cox proportional hazards model was used to examine the multivariable associations between risk factors with OS. All calculation was performed using SAS V9.4.
Results
Among 167 patients, 82 (49%) received pembrolizumab monotherapy with a median OS=34.5 months (95% Confidence Interval (CI):12.2 months-not reached) and 85 (51%) received pembrolizumab/carboplatin/pemetrexed with a median OS=33.7 months (95CI:14.1months-not reached). The median age of patients who received pembrolizumab monotherapy was 66.3 years [57.6, 73.1] with 36.6% female compared to 61.2 years [54.5, 66.9] with 58.1% female in patients that received pembrolizumab/carboplatin/pemetrexed. (Table 1) NLR and ECOG performance status were significant predictors of OS in a multivariate analysis of age, ECOG performance status, immunotherapy regimen, NLR and PD-L1 expression (<50% vs ≥50%). For one unit increased in NLR, the hazard of death increased by 3% (HR (95CI)=1.03 (1.01, 1.05), p=0.0004). For patients with an ECOG performance status of ≥2 the HR was 5.45 (95CI: 2.19-13.57) when compared to an ECOG performance status of 0, p=0.0003. PD-L1 expression was not a significant predictor of survival; PD-L1 expression ≥50% had a HR of 1.27 (95CI: 0.55-2.97) when compared to patients with PD-L1 expression <50%, (p=0.5758).
Table 1: Demographic summary by type of immunotherapy Variable Level Pembrolizumab monotherapy (n=82) Pembrolizumab, carboplatin, pemetrexed (n=85)
Total (n=167) Age Median [IQR] 66.3 [57.6, 73.1] 61.2 [54.5, 66.9] 62.6 [55.5, 72.1] Gender Female 30 (36.6%) 50 (58.8%) 80 (47.9%) Male 52 (63.4%) 35 (41.2%) 87 (52.1%) Race Asian 1 (1.2%) 1 (1.2%) 2 (1.2%) Black or African American 8 (9.8%) 10 (11.8%) 18 (10.8%) White 73 (89%) 74 (87.1%) 147 (88%) Histology Adenocarcinoma 54 (65.9%) 77 (90.6%) 131 (78.4%) Squamous 17 (20.7%) 0 (0%) 17 (10.2%) Other 11 (13.4%) 8 (9.4%) 19 (11.4%) ECOG 0 12 (14.6%) 27 (31.8%) 39 (23.4%) 1 38 (46.3%) 48 (56.5%) 86 (51.5%) >=2 32 (39%) 10 (11.8%) 42 (25.1%) PD-L1 expression positive No 1 (1.2%) 46 (55.4%) 47 (28.7%) Yes 80 (98.8%) 37 (44.6%) 117 (71.3%) PD-L1 TPS (%) Median [IQR] 80 [60, 90] 30 [5, 50] 60 [40, 90] PD-L1 TPS (%) <50% 10 (12.4%) 73 (88%) 83 (50.6%) >=50% 71 (87.7%) 10 (12%) 81 (49.4%) NLR_baseline Median [IQR] 5.7 [3.4, 12.4] 8.8 [5, 13.3] 7.1 [4, 13.3]
Conclusion
In addition to a poor ECOG performance status, we confirmed that baseline NLR is a significant predictor of survival for mNSCLC patients who are receiving pembrolizumab monotherapy or pembrolizumab/carboplatin/pemetrexed, independent of tumor PD-L1 expression. Furthermore, NLR is an accessible test using routine blood work without imposing additional risk and cost to the patients.
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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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P78.05 - Patterns of irAE During First Line Pembrolizumab for NSCLC: Incidence, Risk Factors, and Impact on Clinical Outcome (ID 2974)
00:00 - 00:00 | Author(s): Dwight H Owen
- Abstract
Introduction
Pembrolizumab monotherapy is the preferred treatment option for patients with stage IV non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) tumor expression ≥ 50% and no actionable driver mutations. There is little real word data on immune-related adverse events (irAEs) with first-line pembrolizumab. In this study, we aim to better understand irAE incidence, risk factors, and impact on clinical outcome in treatment naïve patients receiving first-line pembrolizumab therapy.
Methods
We conducted a multicenter, retrospective study of patients with treatment-naïve NSCLC and a PD-L1 expression of ≥50% treated with first line pembrolizumab monotherapy between June 2016 and January 2020. irAEs were determined by treating physician diagnosis and lack of alternative etiologies. Risk factors for irAE occurrence were determined using a logistic regression model. Overall survival (OS) was measured from the date of therapy initiation to death or the last point of follow-up. Survival was estimated by the Kaplan-Meier method. Cox proportional hazards were used to determine the association between irAE and OS while treating irAE as a time-dependent variable. P < 0.05 was considered significant.
Results
In our cohort of 153 patients, the median age was 66 years old (range 41-90); 37% of patients were female, 76.4% of patients had adenocarcinoma, and 21.5% had squamous cell carcinoma. Median follow-up time was 12 months. irAEs occurred in 65 patients (42.4%) with 23 (15.1%) developing irAE CTCAE grade ≥ 3. The most common high grade irAEs were pneumonitis (n=9), colitis (n=6), and hepatitis (n=2). Higher risk for irAE was associated with current tobacco use or cessation of tobacco use <6 months prior to treatment start (odds ratio [OR] 2.27, 95% confidence interval [CI] 1.14-4.52, P=0.02), prior or concurrent radiation therapy (OR 2.03, 95 %CI 1.06-3.90, P=0.03), neutrophil-lymphocyte ratio (NLR) >5 prior to starting therapy (OR 2.33, 95% CI 1.19-4.56, P=0.01), and longer course of pembrolizumab treatment (OR 1.039 per cycle, 95% CI 1.009-1.070, p=0.011). There was no difference in OS between patients who experienced low grade irAEs (<3) and those who did not develop irAEs (HR=0.391, 95% CI 0.124-1.231, p=0.1325) while those who developed high grade irAEs (≥ 3) had worse OS (HR 2.419, 95% CI, 1.117-5.243, p=0.021). Of patients who developed any grade irAEs, those who discontinued pembrolizumab therapy after irAE were found to have worse OS than those who continued therapy (HR 3.178, 95% CI 1.14-8.83, p=0.03).
Conclusion
Risk factors for the development of irAEs during first-line pembrolizumab included current or recent smoking status, NLR >5 prior to treatment start, prior or concurrent radiation therapy, and longer exposure to therapy. Higher grade irAEs and those events leading to discontinuation were associated with worse OS, and no OS benefit was observed in patients with lower grade adverse events. Our study identifies patients at high risk for irAEs who may benefit from closer monitoring during therapy. The lack of survival benefit from irAE in NSCLC patients with high PD-L1 expression has not previously been reported and warrants further investigation.
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P79 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Chemotherapy (ID 256)
- 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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P79.04 - A Phase 2 Trial of Nivolumab and Temozolomide in Extensive Stage Small Cell Lung Cancer: Interim Efficacy Analysis. (ID 3534)
00:00 - 00:00 | Presenting Author(s): Dwight H Owen
- Abstract
Introduction
Effective treatment options are limited in patients with extensive stage small cell lung cancer (ES-SCLC) after progression on first line therapy. Temozolomide is active in ES-SCLC, and has been shown to have immunomodulatory impact on lymphoid cells in patients with advanced cancers. Nivolumab is approved as third line therapy. Here we report the interim efficacy analysis of the ES-SCLC cohort of our phase 2 trial of combination nivolumab and temozolomide in patients with advanced small cell lung cancer as second or third line therapy.
Methods
NCT03728361 is a non-randomized, two-cohort, single-institution, open-label phase 2 study of nivolumab and temozolomide in patients with resistant or refractory ES-SCLC as well as a separate cohort for neuroendocrine tumors. Eligible patients must have progressed after treatment with first line chemotherapy-immunotherapy. Study treatment consists of nivolumab 480 mg IV every 4 weeks and temozolomide 150 mg/m2 for 5 days out of a 28 day cycle (amended from 200 mg/m2). The primary endpoint is best overall response rate (ORR) by RECIST v1.1. For the SCLC cohort, a protocol defined interim analysis would be performed after 15 patients, where ≥ 2 objective responses would be considered sufficient to continue accrual to a total of 25 patients. Progression free survival (PFS) and overall survival (OS) were assessed by the method of Kaplan–Meier. Adverse events were graded using CTCAE v5. Here we will present the interim efficacy analysis after 15 patients were accrued in the ES-SCLC cohort.
Results
Twelve of 15 patients enrolled in the ES-SCLC cohort were evaluable for response at the time of this submission (2 patients were treated under a prior amendment and had not received first line chemotherapy-immunotherapy and were therefore not eligible for primary endpoint analysis and 1 patient did not have imaging as of this submission). Interim efficacy data will be presented for this cohort at the meeting including ORR, PFS, and OS.
Conclusion
Data for combination nivolumab and temozolomide as second or third line treatment for ES-SCLC after first line chemo-immunotherapy will be presented.
