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Corey Jay Langer
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IBS03 - Personalized Management of Elderly Patients with Stage III NSCLC (Ticketed Session) (ID 34)
- Event: WCLC 2019
- Type: Interactive Breakfast Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 07:00 - 08:00, Interlaken (1988)
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IBS03.01 - Managing Locally Advanced NSCLC in the Elderly in 2019 (Now Available) (ID 3322)
07:00 - 08:00 | Presenting Author(s): Corey Jay Langer
- Abstract
- Presentation
Abstract
Managing Locally Advanced NSCLC in the Elderly in 2019
Alternative title: Personalized Management of Elderly Patients with Stage III NSCLC
Corey J. Langer, MD, FACP
Director of Thoracic Oncology
Abramson Cancer Center
Professor of Medicine
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA 19104
In the management of locally advanced (LA) non-small cell lung cancer (NSCLC), at least 10 studies over the past 25 years have shown superiority for chemoradiation over radiation (XRT) alone; more recently, concurrent chemoradiation has proven superior to sequential or asynchronous chemotherapy followed by XRT. Retrospective analyses evaluating outcomes in the elderly receiving these regimens have generally demonstrated similar progression-free (PFS) and overall survival (OS) compared to their younger counterparts on study, albeit with increased toxicity.1,2,3 Generally, those over 70 years of age were under-represented on these trials compared to the NSCLC population at large - while more than 40% of those diagnosed with LA-NSCLC were 70 years of age or older, fewer than 20% of those enrolled on relevant clinical trials were elderly.4 Virtually all of the earlier efforts were cisplatin-based, which made the routine use of this approach in elderly patients outside of clinical trials somewhat problematic, particularly in the face of age-associated co-morbidities that might preclude or limit the application of platinating agents. Since the beginning of the new millenia, non-cisplatin regimens, generally using weekly carboplatin in combination with a taxane or other partner agents active in NSCLC have been shown to yield “equivalent” efficacy with less toxicity. For elderly patients treated outside of a clinical trial, I generally favor weekly carboplatin (AUC 2) coupled with weekly solvent-based paclitaxel (45-50 mg/m2) in conjunction with a minimum dose of 60 Gy administered over a 6-7 week period. At least one trial from Japan conducted exclusively in the elderly with LA-NSCLC showed superior OS for concurrent XRT and low dose daily carboplatin vs XRT alone with median survival of 22.4 mos compared to 16.5 mos in the control group (HR 0.64).5 However, monotherapy with carboplatin during XRT is not considered the standard approach in LA-NSCLC.
The only randomized trial to compare cisplatin- to carboplatin-based combinations in LA-NSCLC was a Japanese study which randomized patients to either MVP during thoracic XRT or to weekly carbo and either irinotecan or paclitaxel; this study showed virtually no difference in long term outcome (18 to 20% 5 year survival), with pacitaxel/carboplatin proving better tolerated.6 These results are dissatisfying, but clearly better than historic controls with XRT alone (5-7% 5 year OS). To date, unfortunately, in North American, we have no prospective, randomized, head-to-head comparisons of cisplatin based treatment vs. paclitaxel/carboplatin or other carboplatin-based regimens in stage IIIA/B NSCLC. Retrospective data from the VA and the SEER database, however, suggest little difference in long term OS.7 The results of RTOG 0617 would tend to validate paclitaxel/carboplaitn as a "viable" regimen in "good prognosis" LA-NSCLC pts with median survival in the 23 to 29 month range for weekly paclitaxel/carboplatin during radical XRT, with no advantage for 74 Gy over 60 Gy or the addition of cetuximab.8 More recently, the PACIFIC trial showed that patients with LA-NSCLC who received “consolidative” durvalumab, a PDL1 inhibitor, for up to a year, after responding to or stabilizing on concurrent chemoradiation, could enjoy a three-fold increase in PFS (16.8 vs 5.6 mos) and a 10% absolute improvement in OS (66.3% vs 55.6%).9 These benefits were both statistically significant (HR 0.68) and clinically meaningful; and the PACIFIC regimen featuring concurrent chemo-radiation followed by durvalumab has emerged as the “standard of comparison” if not the “standard of care” in fit individuals with LA-NSCLC, regardless of age. Of note, the HR for OS benefit in PACIFIC in those 65 years of age and older was 0.76 (95% CI: 0.55 - 1.05) vs 0.62 (95% CI: 0.44- 0.88) for patients under 65. Whether this approach should be applied to patients whose tumors do not harbor PDL1 expression or whose tumors have an oncogenic driver such as EGFR mutations remains controversial.
References:
1. Rocha-Lima, C et al, Cancer 2002
2. Langer, C et al, ASCO 2002
3. Schild, S et al, JCO 2002
4. Auperin et al, JCO 2010
5. Atagi et al, Lancet Oncology, 2012
6. Yamamoto et al, JCO 2010
7. Santana-Davila, R et al, JCO 2015
8. Bradley, J et al, Lancet Oncology 2015
9. Antonia, S et al, NEJM 2018
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MA01 - Oligometastatic Disease (ID 114)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Now Available
- Moderators:Anne Marie Clasina Dingemans, Matthias Guckenberger
- Coordinates: 9/08/2019, 10:30 - 12:00, Copenhagen (1980)
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MA01.08 - Discussant - MA01.05, MA01.06, MA01.07 (Now Available) (ID 3716)
10:30 - 12:00 | Presenting Author(s): Corey Jay Langer
- Abstract
- Presentation
Abstract not provided
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MA05 - Update on Clinical Trials and Treatments (ID 123)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Mesothelioma
- Presentations: 1
- Now Available
- Moderators:Seiki Hasegawa, Enrico Ruffini, Angel Artal
- Coordinates: 9/08/2019, 13:30 - 15:00, Melbourne (1991)
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MA05.10 - Pembrolizumab in the Treatment of Patients with Malignant Pleural Mesothelioma Following Progression After Initial Chemotherapy (Now Available) (ID 2788)
13:30 - 15:00 | Author(s): Corey Jay Langer
- Abstract
- Presentation
Background
Checkpoint inhibitor (CPI) therapies have demonstrated clinical benefit in patients (pts) with malignant pleural mesothelioma (MPM) and are now included in the NCCN guidelines as an acceptable treatment option. Herein, we report our initial experience treating pts with MPM in the palliative second line or greater setting.
Method
Between January 2016 and November 2018, 74 pts with biopsy proven MPM were treated with pembrolizumab every three weeks until confirmed disease progression or unacceptable toxicity. Progression-free survival (PFS) and OS were defined as the time from first pembrolizumab dose to recurrence and death, respectively, or to last contact. Response rates (RR) were measured by a dedicated thoracic radiologist using modified RECIST 1.1 criteria. Adverse events were routinely recorded/scored at each follow up visit. according to CTCAE 4.0 with level of attribution to pembrolizumab.
Result
Demographics of the 74 pt cohort are shown in table 1. Twently-nine (39%) of pts experienceda total of 39 grade 1-2 adverse events, possibly or definitely related to therapy (Table 2). There was one grade 4pneumonitis that resulted in new requirement for oxygen, which resolved with steroids; and one patient experienced leukoencephalopathy that resulted in death. The overall response rate (including only partial responses by modified RECIST 1.1) for the entire cohort was 26%. Median progression free survival and overall survival for the entire cohort were 2.8 months and 7.9 months, respectively.
Table 2: Adverse Events
CTCAE 4.0 Grade
AE Description
1-2
3-4
5
hypothroid
5
arthralgias
8
colitis
3
diarrhea
2
lip lesion
1
pneumonitis
2
1
SICCA syndrome
1
thrombocytopenia
1
dermatitis
1
hypopigmentation
1
nephritis
1
fatigue
1
abdominal pain
1
uveitis
1
transaminitis
1
elvated alk phos
1
leukoencephalopathy
1
pruritis
3
hypercalcemia
3
rash
2
Table 1: Demographics
Age in Years
median (range)
Min
73
(52-92)
Gender
Patients (N=74)
Female
29
39%
Male
55
74%
Histology
Epithelial
58
78%
Sarcomatoid
6
8%
Biphasic
10
14%
# of chemotherapy courses
0
3
4%
1
42
57%
2
22
30%
3-4
7
9%
# of radiotherapy courses
0
42
57%
1
30
41%
2-3
6
8%
Surgical Resection
Have EPD
24
32%
Did not have EPD
50
68%
PDL1
Negative
21
28%
Positive
12
16%
Not Determined
42
57%
Conclusion
Pembrolizumab in the Tx of MPM was reasonably well tolerated in this large, single institution experience. RR, PFS and OS appear remarkably similar to recent published data from a registry study of off-label use of pembrolizumab in pts with MPM in Switzerland and Australia (include reference). Ongoing studies include analysis of PDL-1 and other potential immunotherapy response biomarkers.
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MA25 - Precision Medicine in Advanced NSCLC (ID 352)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 2
- Now Available
- Moderators:Sebastian Defranchi, Karen Kelly
- Coordinates: 9/10/2019, 14:30 - 16:00, Dublin (1997)
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MA25.01 - Pembrolizumab Plus Chemotherapy for Advanced NSCLC Without Tumor PD-L1 Expression: Pooled Analysis of KN021G, KN189 and KN407 (Now Available) (ID 1399)
14:30 - 16:00 | Author(s): Corey Jay Langer
- Abstract
- Presentation
Background
Randomized studies have demonstrated that pembrolizumab plus chemotherapy improves OS, PFS, and ORR compared with chemotherapy alone in patients with advanced NSCLC regardless of tumor PD-L1 expression level. We present a post hoc pooled analysis of pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced NSCLC and no PD-L1 expression (ie, TPS <1%), representing an area of unmet need.
Method
Patients enrolled in KEYNOTE-021 cohort G (nonsquamous; NCT02039674), KEYNOTE-189 (nonsquamous; NCT02578680), and KEYNOTE-407 (squamous; NCT02775435) were included. Patients with nonsquamous NSCLC were randomized to pemetrexed-platinum with or without pembrolizumab; those with squamous NSCLC were randomized to carboplatin-paclitaxel/nab-paclitaxel with or without pembrolizumab. OS, PFS, and ORR were evaluated for the pooled intent-to-treat population. Response was assessed per RECIST v1.1 by blinded independent central review. Across studies, PD-L1 expression was assessed centrally using PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA). Analyses were descriptive.
Result
Of 1298 patients enrolled across the 3 trials, 428 (33%) had PD-L1 TPS <1% (pembrolizumab plus chemotherapy, n=243; chemotherapy alone, n=185) and were included in this analysis. 52% had nonsquamous histology, 63% had ECOG PS of 1. Median (range) follow-up at data cutoff was 10.2 (0.1‒34.9) months. OS, PFS, and ORR were improved with pembrolizumab plus chemotherapy versus chemotherapy alone (Table). Grade ≥3 AEs (all-cause) occurred in 68% of patients receiving pembrolizumab plus chemotherapy versus 72% receiving chemotherapy alone. Immune-mediated AEs and infusion reactions occurred in 26% who received pembrolizumab plus chemotherapy versus 12% who received chemotherapy alone.
ConclusionPembrolizumab + Chemotherapy
n=243
Chemotherapy
Alonen=185
Median (95% CI) OS, mo
19.0 (15.2–24.0)
11.0 (9.2–13.5)
Hazard ratio (95% CI)
0.56 (0.43–0.73)
Median (95% CI) PFS, mo
6.5 (6.2–8.5)
5.4 (4.7–6.2)
Hazard ratio (95% CI)
0.67 (0.54–0.84)
ORR, % (95% CI)
46.9% (40.5%–53.4%)
28.6% (22.3%–35.7%)
Difference (95% CI)
18.3% (9.0%–27.1%)
Our results highlight the clinically meaningful efficacy benefit and acceptable safety profile of pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced NSCLC and no PD-L1 expression. Benefit was consistent with that observed in the overall study populations, suggesting pembrolizumab plus chemotherapy should be considered standard-of-care first-line therapy for all patients with NSCLC, irrespective of PD-L1 expression.
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MA25.04 - Blood-Based Tumor Mutation Burden as a Predictive Biomarker for Outcomes After Pembrolizumab Based First Line Therapy in Metastatic NSCLC (Now Available) (ID 2717)
14:30 - 16:00 | Author(s): Corey Jay Langer
- Abstract
- Presentation
Background
PD-1 blockade with pembrolizumab (P) as monotherapy in patients with PD-L1 TPS > 50% or in combination with platinum based chemotherapy (PC) is the current standard front-line therapy for metastatic non-small cell lung cancer (mNSCLC). We explored the correlation of blood (b) based tumor mutational burden (TMB) using circulating tumor DNA (ctDNA) with outcomes after front line P and PC therapy.
Method
Patients with newly diagnosed metastatic NSCLC starting standard of care front line P-based therapy were enrolled. Plasma was prospectively collected at baseline prior to initiation of P or PC therapy for mNSCLC. A 2.145 megabase (Mb) next-generation sequencing panel was used to assess bTMB. A bTMB cutoff of ≥16 mut/Mb was selected based on previously published data (Gandara et al, Nature 2018). Response was assessed using RECIST 1.1. Durable clinical benefit (DCB) was defined as complete response/ partial response/ stable disease that lasted > 6 months. Correlations were made for patient demographics, tumor characteristics, DCB, progression free survival (PFS), and overall survival (OS) using logistic regression and Cox proportional hazards models. Significance was determined at the 0.05 level.
Result
66 pts with mNSCLC were enrolled, median age 67 years (range 47-89), current or ex-smokers (n=61, 92%). Thirty-one patients (47%) received P (all PD-L1>50%); 35 received platinum-pemetrexed based PC. At the time of data cut off, median OS for P was 14.8 months, and not reached for PC. bTMB was evaluable for 52 patients (n=26 P, 26 PC), median bTMB was 16.8 mutations per Mb (mut/Mb, range 1.9-52.5). There was no correlation between bTMB and tumor PD-L1 (p=0.28). Median bTMB for patients achieving DCB was higher than for those with no clinical benefit, 21.3 mut/Mb vs. 12.4 mut/Mb, p=0.004. For patients with bTMB ≥ 16 mut/Mb, median PFS was 13.8 vs. 4.7 months for patients with bTMB <16 mut/Mb (HR 0.27 [0.13-0.55]). Median OS was not reached for bTMB ≥ 16 mut/Mb (HR 0.47 [0.20-1.1]). Loss of function mutations in STK11, KEAP1, or PTEN, or ERBB2 exon 20 insertion were enriched in patients with no clinical benefit. Combined score using bTMB ≥ 16 mut/Mb and mutations in STK11, KEAP1, or PTEN, or ERBB2 exon 20 insertions resulted in improved prediction for DCB; PFS HR of 0.18 [0.08-0.41] and OS HR of 0.27 [0.10-0.73].
Conclusion
Our early results suggest that bTMB using plasma ctDNA may predict therapeutic outcomes after first line P-based therapy in mNSCLC. Loss of function mutations in STK11/KEAP/PTEN and ERBB2 exon 20 insertion mutations appear to be negative predictors of benefit. As the sample size is limited and findings are reported on a pooled group of P and PC patients, the role of bTMB and response to P and PC based therapy separately should be validated in a larger prospective study.
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OA04 - Immuno Combinations and the Role of TMB (ID 126)
- Event: WCLC 2019
- Type: Oral Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:Solange Peters, Martin Reck
- Coordinates: 9/08/2019, 15:15 - 16:45, Copenhagen (1980)
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OA04.05 - KEYNOTE-021: TMB and Outcomes for Carboplatin and Pemetrexed With or Without Pembrolizumab for Nonsquamous NSCLC (Now Available) (ID 2630)
15:15 - 16:45 | Presenting Author(s): Corey Jay Langer
- Abstract
- Presentation
Background
KEYNOTE-021 cohort C was the first study to show antitumor activity for pembrolizumab plus platinum-based chemotherapy in previously untreated advanced nonsquamous NSCLC; the combination significantly improved efficacy vs platinum-based chemotherapy alone in cohort G. We explored the relationship between TMB and outcomes in KEYNOTE-021 cohorts C and G.
Method
All patients in cohort C received pembrolizumab plus carboplatin and pemetrexed. Patients in cohort G were randomized 1:1 to pembrolizumab plus carboplatin and pemetrexed or carboplatin and pemetrexed alone. TMB was determined by whole-exome sequencing of tumor and matched normal DNA. Association of TMB (continuous, log10 transformed) with outcomes for pembrolizumab plus chemotherapy and chemotherapy alone were assessed using logistic regression for ORR and Cox proportional hazards models for PFS and OS adjusted for ECOG PS; statistical significance was determined at the 0.05 level without multiplicity adjustment. The correlation of TMB (continuous, log10 transformed) with PD-L1 TPS (square root scale) was assessed in the combined population. The clinical utility of TMB for ORR using a prespecified TMB cutpoint of 175 Mut/exome (~13 Mut/Mb by FoundationOne CDx) was assessed for pembrolizumab + chemotherapy.
Result
TMB data were evaluable for 70 patients: 12/24 (50.0%) in cohort C, 32/60 (53.3%) in the cohort G pembrolizumab plus chemotherapy arm, and 26/63 (41.3%) in the cohort G chemotherapy only arm; median age was 65 years (IQR, 57-70) and 61% were female. Baseline characteristics were generally similar in the TMB-evaluable and total populations. TMB as a continuous variable was not significantly associated with ORR, PFS, or OS for pembrolizumab plus chemotherapy (one-sided P = 0.180, 0.187 and 0.081, respectively) or chemotherapy alone (one-sided P = 0.861, 0.795 and 0.763, respectively). There was no significant correlation between TMB and TPS (r=0.12, P=0.34). ORR (95% CI) in patients treated with pembrolizumab plus chemotherapy was 60.8% (38.5-80.3) in the 23 patients with TMB <175 and 71.4% (47.8-88.7) in the 21 patients with TMB ≥175.
Conclusion
In this exploratory analysis, TMB was not significantly associated with efficacy of pembrolizumab plus carboplatin and pemetrexed or carboplatin and pemetrexed alone as first-line therapy for metastatic nonsquamous NSCLC. TMB was not significantly correlated with PD-L1 expression. Among pembrolizumab plus chemotherapy-treated patients, ORR was high in both the TMB low and high subgroups. Sample size is a limitation of this study; exploration in larger datasets is required to understand any differential efficacy of pembrolizumab plus chemotherapy vs chemotherapy alone based on TMB status.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-63 - Impact of Prior Radiation Pneumonitis on Incidence of Immunotherapy Related Pneumonitis (ID 662)
09:45 - 18:00 | Author(s): Corey Jay Langer
- Abstract
Background
Patients with a history of radiation pneumonitis (RP) requiring steroids have generally been excluded from immuno-oncology (IO) trials of PD-1/PDL-1 monoclonal antibodies for safety concerns. The risk of IO-associated pneumonitis (IOP) in this group of patients (pts) is therefore unknown. We evaluated the frequency of IOP in pts who had prior RP.
Method
We evaluated all pts with non-small cell lung carcinoma (NSCLC) treated at our institution between 2011 and 2018 who were diagnosed with RP and at a later point received IO. Demographics, tumor characteristics, steroid use and outcomes were extracted from the electronic medical record. Median overall survival (mOS), median progression free survival (mPFS), and median time to treatment failure (mTTF) from the start of IO were estimated from Kaplan-Meier curves.
Result
We identified 29 pts: median age at diagnosis 63 yrs, 51.7% male, none had received prior targeted therapies. IO treatments were: atezolizumab (2), durvalumab (2), nivolumab (12), and pembrolizumab (13). Median time from RP diagnosis to start of IO was 14.2mo (2.2-75 mo). 23 pts (79%) had experienced prior grade ≥ 2 RP requiring steroids. Only 2 of the 29 pts (6.9%) developed IOP. Both pts had required steroids for prior RP and both received durvalumab; one pt was on prednisone ≥ 10mg at the start of IO. Both required steroid treatment of IOP, are still on IO and have not progressed (censored at 8.3mo and 9.9mo). OS and PFS after IO are similar (Table 1) whether or not pts required treatment for RP or were on prednisone ≥ 10 mg (or steroid equivalent) at the start of IO.
Table 1: IO outcomes based on RP history and steroid use at start of IO
RP Grade ≥ 2
n=23 (95% CI)
RP Grade < 2
n=6 (95% CI)
Prednisone ≥ 10mg
n=7 (95% CI)
Prednisone < 10mg
n=22 (95% CI)
All patients
n = 29 (95% CI)
mPFS (mo)
5.44 (2.1-12.6)
12.95 (0.95-)
6.16 (2-)
5.44 (2.1-)
6.16 (2.4-)
mOS (mo)
6.6 (3.93-13.8)
NR
14.3 (5.3-)
8 (3.4-16.8)
8 (5.3-15)
mTTFa (mo)
2.3 (1.9-4.8)
2.3 (1.9-)
4.4 (2-)
2.3 (1.9-10.9)
2.75a (2-7)
an=28: 1 pt lost to follow up after start of IO
Conclusion
In our cohort, the incidence of IOP after RP is low and similar to the rate of pneumonitis reported with pembrolizumab in pts with prior exposure to thoracic radiation.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-02 - Effect of Chemotherapy, Chemoimmunotherapy, and Immunotherapy on Parameters of T Cell Exhaustion in Metastatic Non-Small Cell Lung Cancer (ID 1880)
10:15 - 18:15 | Author(s): Corey Jay Langer
- Abstract
Background
The pharmacodynamic immune response to anti-PD-1 immunotherapy can be tracked in the peripheral blood of cancer patients and is associated with response to therapy. However, it is unclear how chemotherapy and chemoimmunotherapy affect T cell activity. Given the established role of these treatments in Non-Small Cell Lung Cancer (NSCLC), we sought to compare the impact of chemotherapy, chemoimmunotherapy, and immunotherapy on T cell immunity.
Method
We prospectively collected blood samples in pts beginning chemotherapy, chemoimmunotherapy, or immunotherapy for metastatic NSCLC at baseline and with each cycle. Peripheral blood mononuclear cells were stained for immune markers and analyzed using 26 parameter flow cytometry. Immune response was characterized by increased expression of Ki67 on PD-1 expressing CD8 T cells. Statistical analysis was performed using paired t-test or Wilcoxon matched pairs analysis based on normality of data. All patients had CT scans with full RECIST 1.1 and tumor volume measurements.
Result
We analyzed 28 pts (63% female, median age = 65.5). 9 pts received chemotherapy, 12 pts immunotherapy, and 7 pts chemoimmunotherapy. Both immunotherapy (p = 0.001) and chemoimmunotherapy (p=0.016) resulted in an immune response that peaked at 3 weeks compared to baseline (Figure). No immune response was identified with chemotherapy (p=0.734). Immune response was detected in exhausted T cells (PD1+CD39+ CD8) for both immunotherapy (p =0.007) and chemoimmunotherapy (p =0.031). In addition, chemoimmunotherapy induced activation of CD27+CCR7+ memory CD8 T cells (p=0.0313), not seen with immunotherapy (p= 0.871).
Conclusion
Chemoimmunotherapy and immunotherapy, but not chemotherapy, induced a significant immune response in the peripheral blood, peaking at 3 weeks. While immunotherapy and chemoimmunotherapy both targeted an exhausted population, chemoimmunotherapy induced an immune response in exhausted and memory T cells. We have collected more samples, and at time of the WCLC will present these data, as well as correlation with RECIST responses.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-26 - Outcomes in Patients with Compound Epidermal Growth Factor Receptor (EGFR) Mutations After Treatment with Tyrosine Kinase Inhibitors (TKIs) (ID 1090)
10:15 - 18:15 | Author(s): Corey Jay Langer
- Abstract
Background
TKIs targeting EGFR have changed the therapeutic paradigm for patients (pts) with non-small cell lung cancer (NSCLC) harboring classic sensitizing mutations in EGFR (L858R and Exon 19del). Less is known about the efficacy of TKIs when a sensitizing mutation is co-existent with another, not resistance-associated EGFR mutation (compound EGFR mutations). We report the outcomes of pts with de novo compound EGFR mutations treated with TKIs.
Method
We identified pts with compound EGFR mutated NSCLC (plasma or tissue detection) treated at a single center. All disease-associated EGFR mutations were included with the exception of T790M and C797S. Time to treatment failure (TTF) was calculated from the start of TKI therapy until treatment discontinuation for any reason (i.e. disease progression, toxicity, pt choice or death). Overall survival (OS) was calculated from the start of TKI until death. Median OS (mOS) and TTF (mTTF) were estimated from Kaplan-Meier curves.
Result
24 pts with compound EGFR mutations were identified (median age 60, 67% female, 29% never smokers) between 2011 and 2018 (Table 1). Of the 16 (67%) who received a TKI, the most common mutation was G719X (n=9). Exon 19 deletions (del) were present in 2 patients (1 with G719X). L858R was found in 5 patients. Of the 8 pts who did not receive a TKI, 4 had early stage NSCLC that never progressed, 2 had local recurrence treated with surgery/radiation and 2 had metastatic recurrence. Among those treated with a TKI, the mTTF was 13.6 months (mo) and mOS was 32.7 mo. There was no difference in mTTF between erlotinib (n=10) and afatinib (n=6) (13.6 vs. 8.8 mo, log rank p=0.67). Median follow up was 33 mo. In 7 pts who had both baseline tissue and plasma testing, plasma detected all non-classic mutations.
Conclusion
The mOS and mTTF in this cohort of pts with compound EGFR mutations compare favorably to the historical progression free survival and mOS for pts with classic sensitizing mutations in EGFR treated with erlotinib or afatinib.
Table 1: Compound EGFR mutations (n=24)
Exon 3
Exon 18
Exon 19
Exon 20
R108K
E709X
del
S768I
V769M
R776H
Exon 18
G719X
5
1
8
1
1
Exon 19
del
1
Exon 21
L858R
3
2
L861Q
1
1
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PR02 - Press Conference (ID 387)
- Event: WCLC 2019
- Type: Press Conference
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 10:30, CC7.1 A&B
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PR02.06 - KEYNOTE-021: TMB and Outcomes for Carboplatin and Pemetrexed With or Without Pembrolizumab for Nonsquamous NSCLC (ID 3610)
09:45 - 10:30 | Presenting Author(s): Corey Jay Langer
- Abstract
Abstract not provided
