Virtual Library
Start Your Search
Mark K. Doherty
Author of
-
+
MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
-
+
MA25.11 - Clinical and Molecular Predictors of Outcome in Patients with EGFR mutant NSCLC Brain Metastases treated with RT (ID 14529)
14:40 - 14:45 | Author(s): Mark K. Doherty
- Abstract
- Presentation
Background
Brain metastases(BM) develop in ~45% of patients with EGFR mutant(EGFRm) non-small cell lung cancers(NSCLC). There are limited reports on clinical/molecular factors associated with BM outcomes after radiotherapy in EGFRm NSCLC patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
We identified patients with EGFRm NSCLC who presented with or developed BM and had their lung tumor resected. Clinical, demographic and TP53 status were collected from medical/pathology records. Whole-Exome Sequencing of the primary tumor was performed. Overall survival(OS) and intracranial progression(IP) were defined from start of BM treatment and correlated with clinical/molecular features. IP was defined from the date of BM treatment until any brain failure, either local(previously present BM) or distant(development of new BM). Categorical and continuous covariates were tested by Fisher exact or Mann-Whitney test, respectively. OS by Kaplan-Meier with groups compared by log-rank. For each model the Harrell Concordance Index(CI) was performed.
4c3880bb027f159e801041b1021e88e8 Result
From 41 eligible patients with BM, 9 were excluded due to sequencing quality. Of the 32 remaining patients, 20 (62%) had their BM treated with WBI (15 WBI alone and 5 TKIàWBI), 12 (38%) with TKI±SRS (9 TKI àSRS; 2 TKI alone and 1 SRS alone). Median age at BM was 59.5 years(y). Most of the cohort were female(81%), non-smoker(78%), non-Asian(62%) and 50% presented as stage III or higher at diagnosis. An EGFR exon 19 mutation was present in 72% of patients, 25% had 2 or more EGFRm, 15% with additional driver mutations and 53% with TP53 co-mutation. At a median follow-up of 1.21-y, no clinical/molecular factors(treatment, age, gender, ethnicity, smoking status, stage at presentation, EFGR exon 19 versus 21, number of EGFRm, additional driver mutations, TP53 co-mutation) correlated with survival. There was a trend for longer survival for patients treated with TKI±SRS(median 3.4y) compared to WBRT±TKI(median 1.4y); p=0.08 and for age at BM ≤59.5y(median 2.5y) compared to >59.5y (median 1.4y); p=0.2. Higher risk of IP was observed in younger patients (age as continuous variable) with HR of 0.94(95%CI 0.88-1.0), p=0.04; favoring older patients and remained significant after accounting for treatment modality on multivariate analysis p=0.03. No additional clinical/molecular factors correlated with IP.
8eea62084ca7e541d918e823422bd82e Conclusion
In our study, younger age at BM treatment was associated with higher IP. We also observed a trend for longer OS for younger patients(≤59.5y) and for patients treated with TKI±SRS. Our data suggest that younger patients with EGFR BM should undergo close intracranial follow up and that future studies to define the benefit of brain-directed multimodality treatment are warranted.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
-
+
P1.01-16 - First-Line Pembrolizumab With or Without Chemotherapy in PD-L1 positive NSCLC: A Network Meta-Analysis of Randomized Trials. (ID 12147)
16:45 - 18:00 | Presenting Author(s): Mark K. Doherty
- Abstract
Background
Pembrolizumab has replaced platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC) with tumor PD-L1 expression >/=50%. Among PD-L1 unselected patients, pembrolizumab + chemotherapy is superior to chemotherapy alone. This network meta-analysis compared pembrolizumab alone with pembrolizumab + chemotherapy in patients with >/=50% PD-L1 positive NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
Using the Keynote 024 and 189 (PD-L1 >/=50% subgroup) trials, an indirect network was constructed to compare pembrolizumab and pembrolizumab + chemotherapy through the chemotherapy control arms of each trial. Baseline characteristics and chemotherapy outcomes in both trials were examined for heterogeneity. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs) including immune-related adverse events (irAE) were extracted from trial results. AE results were unavailable for the PD-L1 >/=50% subgroup of KN189, so overall AE results were used. Comparisons were expressed as hazard ratios (HRs) for survival outcomes, and as risk difference (RD) for ORR and toxicity.
4c3880bb027f159e801041b1021e88e8 Result
507 patients were included: 154 on pembrolizumab, 357 on chemotherapy and 410 on combination. Baseline characteristics of patients in both trials were similar in age, sex, performance status and smoking history. Both trials also had similar chemotherapy outcomes (PFS 6 vs 5 mos) suggesting similar patient prognosis. Network meta-analysis showed no difference between pembrolizumab + chemotherapy and pembrolizumab alone in OS (HR 0.70, 95%CI 0.38-1.30, p=0.26) or PFS (HR 0.72, 95%CI 0.45-1.16, p=0.18), but combination therapy was associated with higher ORR (+21.5%, 95%CI 4.83-38.2%, p=0.011). Overall and grade 3-5 AE rates were higher with combination treatment compared with pembrolizumab alone, but irAE appeared less common with combination treatment (table).
8eea62084ca7e541d918e823422bd82e Conclusion
Among patients with >/=50% PD-L1 positive NSCLC, pembrolizumab + chemotherapy did not improve OS or PFS compared with pembrolizumab alone, but was associated with higher ORR. Lower rates of irAE with combination therapy are interesting and warrant further study.
6f8b794f3246b0c1e1780bb4d4d5dc53Adverse events for Pembrolizumab + Chemotherapy vs Pembrolizumab Alone
All Grade Adverse Events
Grade 3-5 Adverse Events
Risk Difference (%)
95% CI
p-value
Risk Difference (%)
95% CI
p-value
Any
17.4
8.8, 26.0
<0.001
18.2
4.8, 31.5
0.008
Led to Discontinuation
9.4
1.3, 17.6
0.023
5.7
-1.2, 12.7
0.11
Led to Death
2.1
-2.7, 6.9
0.40
2.1
-2.7, 6.9
0.40
Nausea
37.2
24.7, 49.7
<0.001
2.0
-1.8, 5.8
0.31
Anemia
38.4
26.4, 50.5
<0.001
18.3
9.2, 27.4
<0.001
Fatigue
20.9
8.9, 32.9
<0.001
5.2
0.6, 9.8
0.025
Decreased appetite
14.9
3.5, 26.2
0.01
3.7
0.7, 6.7
0.017
Diarrhea
8.6
-2.0, 19.2
0.11
-0.4
-5.1, 4.4
0.89
Neutropenia
24.9
14.9, 34.9
<0.001
17.3
9.4, 25.1
<0.001
Vomiting
18.3
8.4, 28.3
<0.001
0.8
-2.7, 4.2
0.67
Pyrexia
-0.4
-9.1, 8.3
0.93
NA
Constipation
10.6
0.7, 20.5
0.036
NA
Thrombocytopenia
15
7.1, 23.0
<0.001
6.3
0.6, 12.0
0.029
All Grade Immune-Related Adverse Events
Grade 3-5 Immune-Related Adverse Events
Any
-13.7
-23.7, -3.74
0.007
-4.6
-11.2, 1.6
0.15
Hypothyroidism
-3.6
-9.4, 2.3
0.23
NA
Hyperthyroidism
-5.5
-11, 0.1
0.051
NA
Pneumonitis
-3.2
-8.1, 1.7
0.20
-1.2
-5, 2.5
0.54
Infusion reaction
-1.7
-6.0, 2.5
0.43
NA
Severe skin reaction
-4.4
-8.4, -4.3
0.03
-0.4
-7.8, -0.1
0.047
Colitis
0.3
-2.3, 2.9
0.84
-0.6
-2.5, 1.4
0.58
Myositis
-1.7
-3.9, 0.5
0.14
NA
Hypophysitis
0.1
-1.4, 1.6
0.91
NA
Nephritis
1.1
-0.7, 2.9
0.24
0.8
-0.9, 2.6
0.35
-
+
P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.01-79 - Neurological Death is Common in Patients With EGFR Mutant Non-Small Cell Lung Cancer (ID 11167)
16:45 - 18:00 | Author(s): Mark K. Doherty
- Abstract
Background
Patients with EGFR mutant non-small cell lung cancer (EGFRmNSCLC) have a high incidence of brain metastases (BM). We sought to determine the rate of neurologic death in EGFRmNSCLC patients diagnosed with brain metastases.
a9ded1e5ce5d75814730bb4caaf49419 Method
A single-institution prospectively managed database identified 204 patients with EGFRmNSCLC treated for brain metastases between 2000 and 2016. We estimated actuarial survival rates using the Kaplan-Meier method. The incidence of neurologic death (ND) was determined using a competing risks analysis. ND was correlated to clinical and treatment variables using Fisher’s exact test. Survival was calculated from the date of BM diagnosis. We defined neurologic death as death due to brain metastases or leptomeningeal disease.
4c3880bb027f159e801041b1021e88e8 Result
Fifty-six percent of patients had BM at the time of initial diagnosis. The initial BM treatment was up front stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), or tyrosine-kinase inhibitor (TKI) alone in 22, 60, and 18 percent of patients, respectively. Two-year rates of OS in these subgroups were 64%, 38%, and 50%, respectively (p=0.016). The 5-year rate of neurologic death was 38%. Thirty-four percent died of non-neurologic causes, 8% died of unknown causes, and the remaining patients were alive at last follow-up. Median survival (MS) was 19 months; MS in patients who died of non-neurologic causes and neurologic causes was 23, and 15 months, respectively. Of age, staging, BM at diagnosis, history of TKI therapy, initial treatment of BM, staging at diagnosis, and leptomeningeal disease at diagnosis (LMD), only LMD was significantly associated with ND (p=0.047).
8eea62084ca7e541d918e823422bd82e Conclusion
Neurologic death due to EGFRmNSCLC BM was more common in our cohort than has been previously reported, highlighting the need for dedicated studies focused on the best management of BM in this population.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
-
+
P3.16-07 - The Impact of Clinical and Molecular Profile of Resected EGFR-Mutant Non-Small Cell Lung Cancer on the Risk of Developing Brain Metastases (ID 13339)
12:00 - 13:30 | Author(s): Mark K. Doherty
- Abstract
Background
Brain metastases are common in non-small cell lung cancers (NSCLC) with activating EGFR mutations (EGFRm), occurring in 44%-63% of patients. To date, there are no known clinical or molecular factors to predict the risk of brain metastases in these patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
In this retrospective single-institution study, we identified 106 patients with EGFRm NSCLC who underwent surgery for primary lung tumor. Clinical and demographic data was collected from electronic records. Whole Exome Sequencing (WES) of the primary tumor was performed utilizing the Agilent SureSelect Exome v6+COSMIC baits followed by sequencing on the Illumina HiSeq2500 platform. Development of brain metastases was correlated with clinical/pathologic features, EGFR mutation type, co-mutation of EGFR and other frequently mutated genes; and non-synonymous tumor mutation burden (TMB). Statistical analysis used Fisher exact test for categorical variables, Mann-Whitney test for continuous variables of association with the risk of developing brain metastases, and Gray’s test for the probability of brain metastases over time.
4c3880bb027f159e801041b1021e88e8 Result
Of 106 patients who underwent surgical resection of primary EGFRm NSCLC, WES was successful for 73: 51 (70%) females, 52 (71%) never smokers, 38 (52%) stage I, 14 (19%) stage II and 21 (28%) stage III; 42 (57%) EGFR exon 19 mutation, 30 (41%) exon 21, 1(1%) Exon 20 insertion mutation.
Twenty-five patients (34%) developed brain metastases. Patients with brain metastases were younger (median age 61 vs. 65 years, p=0.021), had more advanced stages (p=0.012), with a trend towards higher rates in females (p=0.066). One patient with brain metastases had de-novo EGFR T790M mutation in the primary tumor. No difference was seen regarding smoking history, EGFR mutation type, TP53 co-mutation, and median TMB. The 5-year probability of brain metastases increased with increasing stage (14% stage I; 43% stage II, [HR=3.00], 44% stage III, [HR=3.13], p=0.03), and a trend towards higher probability among females (33% vs. 19%; HR=0.39 for males, p=0.074), and younger patients (37% <65 years vs. 15% >65, HR=0.37 in older patients, p=0.042). There was no difference in probability of brain metastases based on smoking history, ethnicity, EGFR type (33% exon 19 vs. 22% exon 21, p=0.28), TP53 co-mutation (31% vs. 27% without TP53, p=0.59), or TMB (24% TMB≤2.87 vs. 32% TMB>2.87non-synonymous mutations/Mb, p>0.99).
8eea62084ca7e541d918e823422bd82e Conclusion
While our findings suggest that younger age, advanced stage, and female sex may be associated with the development of BM in EGFRm NSCLC, we could identify no molecular predictor of BM based on EGFR subtype, TP53 co-mutation or TMB.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
PC08 - The Great Oligometastatic Debates (ID 847)
- Event: WCLC 2018
- Type: Pro-Con Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 105
-
+
PC08.07 - Debate #3: Brain Metastases with a Driver Mutation Should Be Treated with Systemic Therapy First (PRO) (ID 11637)
14:30 - 14:40 | Presenting Author(s): Mark K. Doherty
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
