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Jose Manuel Trigo
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MA04 - Health Policy and the Real World (ID 217)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 16:45 - 17:45, Scientific Program Auditorium
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MA04.07 - Comparative Clinical Outcomes for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutations and Common EGFR Mutations (ID 3390)
16:45 - 17:45 | Author(s): Jose Manuel Trigo
- Abstract
- Presentation
Introduction
Approximately 85–90% of the mutations seen in EGFR-mutant non-small cell lung cancers (NSCLCs) are common mutations (cEGFR), Exon 19 deletions and Exon 21 L858R. Up to 10% of EGFR-mutant NSCLC harbors Exon 20 insertion mutations (Exon20ins). We conducted a retrospective cohort study using real-world data to compare clinical outcomes between patients harboring Exon20ins and cEGFR.
Methods
This retrospective cohort study included patients from the Flatiron Health database (1 January 2011 through 31 May 2020) who had advanced NSCLC. The objectives of the study were to assess the prognostic value of Exon20ins compared with cEGFR (start date of first-line therapy as the index date) and the effect of tyrosine kinase inhibitor (TKI) treatment between the groups (start date of first TKI line as the index date). Analysis was stratified by line of TKI use. Endpoints included real-world overall survival (rwOS), progression-free survival (rwPFS), and time to next therapy (rwTTNT) and were analyzed using multivariable Cox proportional hazards model and summarized by Kaplan-Meier method.
Results
Among 62,464 patients with advanced NSCLC, 181 with Exon20ins and 2833 with cEGFR met eligibility criteria. Population demographics between the groups were comparable with minor exceptions. With median 34-month follow-up, Exon20ins was associated with a 75% increased risk of death (adjusted hazard ratio [adjHR] of 1.75 [95%CI, 1.45–2.13]; p˂0.0001); median rwOS was 16.23 (95%CI, 11.04–19.38) for Exon20ins and 25.49 months (95%CI, 24.48–27.04) for cEGFR (Table). The estimated 5-year survival rate for Exon20ins is 8% compared with 19% for cEGFR.
The predictive value of TKI treatment, stratified by line, was assessed in 76 Exon20ins and 2749 cEGFR patients who were treated with TKIs. With median 20.6-month follow-up, there was a 170% increase in risk of progression or death associated with Exon20ins (adjHR of 2.7 [95% CI, 2.06–3.55]; p˂0.0001); median rwPFS was 2.86 months (95%CI, 2.14–3.91) compared with 10.45 months (95%CI: 10.05–10.94) for cEGFR. Furthermore, there was a 170% increased risk of death (adjHR of 2.70 [95% CI, 2.04–3.57]; p˂0.0001) associated with Exon20ins; median rwOS was 7.46 months (95%CI, 5.45–13.34) for Exon20ins and 25.49 months (95%CI, 24.28–26.81) for cEGFR (Table).
Conclusion
Patients with Exon20ins have a worse prognosis compared with patients with cEGFR. Furthermore, EGFR TKI treatment was substantially less effective for patients with Exon20ins, as the risk of disease progression and mortality was higher compared with patients with cEGFR. These findings highlight the need for new treatment options for Exon20ins.
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OA04 - New Data from Rare EGFR Alterations (ID 223)
- Event: WCLC 2020
- Type: Oral
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 11:45 - 12:45, Scientific Program Auditorium
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OA04.04 - Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer (ID 3031)
11:45 - 12:45 | Author(s): Jose Manuel Trigo
- Abstract
- Presentation
Introduction
Despite sharing similar tumor biology to other epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) tumors, no targeted therapies have been approved for NSCLC harboring EGFR Exon 20 insertion mutations (Exon20ins). The standard of care remains platinum-based chemotherapy for the front-line, with no clear subsequent options available. Amivantamab (JNJ-61186372) is a novel, fully human EGFR-MET bispecific antibody with immune cell-directing activity that targets activating and resistance EGFR mutations, as well as MET mutations and amplifications, and has received FDA Breakthrough Therapy Designation for the treatment of patients with EGFR Exon20ins NSCLC after platinum-based chemotherapy. Here we present updated results on the Exon20ins cohort from the CHRYSALIS study (NCT02609776).
Methods
The dose escalation phase enrolled patients with advanced NSCLC to determine the recommended phase 2 dose (RP2D) of 1050 mg (1400 mg for ≥80 kg) amivantamab. The dose expansion phase assessed the safety and efficacy of amivantamab in patients with EGFR- and MET-mutant NSCLC treated at the RP2D. Disease response was assessed by the investigator per RECIST v1.1 and is presented for those patients with Exon20ins NSCLC who had progressed on prior platinum-based chemotherapy, were treated at the RP2D, and had at least 3 post-baseline disease assessments (18 weeks) or discontinued, progressed, or died prior to the 3rd assessment (the Post-Platinum Cohort). The data cutoff date was 8 Jun 2020.
Results
In the Post-Platinum Cohort (n=81), median age was 62 (42 – 84), 59% were women, 49% were Asian, median prior lines of therapy was 2 (1 – 7), and 53% were never-smokers. At a median follow-up of 6.5 months (1.1 – 29.3), investigator-assessed overall response rate (ORR) was 36% (29/81; 95% CI, 25 – 47), with all responders achieving partial response (PR). The clinical benefit rate (≥PR or stable disease ≥11 weeks) was 73% (59/81; 95% CI, 62 – 82). Responses were durable at a median of 6.8 months (95% CI, 5.0 – not reached) with ongoing responses in 18/29 (longest at 16+ months). Median progression-free survival was 8.3 months (95% CI, 5.5 – 12.7) and median overall survival was 22.8 months (95% CI, 14.0 – not reached).
Among all phase 1 patients, across a variety of EGFR genomic alterations and lines of therapy, treated with amivantamab monotherapy at the RP2D (n=258), the most common adverse events (AEs) were rash (78%), infusion related reaction (IRR; 65%), and paronychia (40%). Additional EGFR-related AEs were stomatitis (19%), pruritus (19%), and diarrhea (11%). Grade ≥3 AEs were reported in 39% of patients; 14% were considered treatment-related, with rash (3%) and IRR (2%) being most frequent. No treatment-related deaths were reported. The incidence of treatment-related AEs leading to dose reduction and discontinuation was 10% and 3%, respectively.
Conclusion
Amivantamab treatment led to promising efficacy with durable responses in patients with EGFR Exon20ins NSCLC post-platinum doublet and continues to demonstrate a manageable safety profile in over 250 patients treated at the RP2D. A phase 3 study, PAPILLON, evaluating amivantamab in combination with chemotherapy in the front-line setting is in planning stages.
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P52 - Staging - Prognosis and Staging (ID 186)
- Event: WCLC 2020
- Type: Posters
- Track: Staging
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P52.05 - Lung Cancer Symptoms at Diagnosis: Data from the Thoracic Tumors Registry (TTR Study). (ID 3023)
00:00 - 00:00 | Author(s): Jose Manuel Trigo
- Abstract
Introduction
Lung cancer is the most common cancer worldwide and is the leading cause of cancer death in Western countries. Despite its high incidence and mortality there are few studies that describe its symptoms at diagnosis and their relationship with tumor stage and tobacco use. The objective of this study is to describe the frequency of the most common symptoms of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) at diagnosis and their connection with stage of disease and smoking habit.
Methods
This was a case series study that analysed cases collected from the Thoracic Tumour Registry (TTR) sponsored by the Spanish Lung Cancer Group (SLCG) from August 2016 to June 2019.
Results
9,876 patients were included. 74% male, the median age was 65 years (57-72), 12% were never smokers. The most frequent histologic type was adenocarcinoma (52%) followed by squamous cell carcinoma (24%) and small cell lung cancer (12.5%). 46.6% of the patients was stage IV at diagnosis. The most common symptoms were cough (33.9%) and dyspnoea (26.7%). No symptom was present in 59% of patients diagnosed stage I NSCLC and in 27.7% of patients stage IV NSCLC. The number of symptoms was similar across the respective smoking categories in NSCLC and differences between the symptoms analysed did not exceed 7% in any case
TABLE:
Table. 1 Symptom description by tobacco consumption: NSCLC
Symptoms at diagnosis+
Never smokers**
Ex-smokers**
Current smokers**
p-trend
Cough
387 (34.1)
1,310 (31.7)
1,099 (34.5)
0.163
Pain
318 (28.0)
990 (24.0)
1,008 (31.6)
<0.001
Dyspnoea
330 (29.1)
1,014 (24.5)
823 (25.8)
0.365
Haemoptysis
70 (6.2)
511 (12.4)
389 (12.2)
<0.001
Weight loss
223 (19.7)
678 (16.4)
842 (26.4)
<0.001
Anorexia
66 (5.8)
185 (4.5)
226 (7.1)
0.001
Asthenia
114 (10.1)
315 (7.6)
331 (10.4)
0.024
Superior vena cava syndrome
3 (0.3)
6 (0.1)
15 (0.5)
0.039
Aphonia or voice alterations
331 (2.7)
100 (2.4)
104 (3.3)
0.085
Number of symptoms++
0
1
2
3
4 or more
341 (30.1)
252 (31.0)
236 (20.8)
127 (11.2)
78 (6.9)
1,531 (37.0)
1,121 (27.1)
812 (19.6)
427 (10.3)
242 (5.8)
879 (27.6)
887 (27.8)
694 (21.8)
454 (14.2)
272 (8.4)
<0.001
0.263
0.113
<0.001
<0.001
**Never smoker: participant smoked less than 100 cigarettes in lifetime. Ex-smoker: stopped smoking more than 1 year before diagnosis. Current smoker: declared smoking during the year before diagnosis. 89 participants had unknown tobacco consumption.
+Percentages calculated as a total of the sample.
++Totals calculated for each smoking category.
Conclusion
In conclusion, this study provides valuable information on the frequency and type of lung cancer symptoms at diagnosis and their relationship with stage and tobacco use. The most relevant findings are that 28% of stage IV lung cancers do not present any symptoms at diagnosis, and that there are no relevant differences in symptom presentation by reference to smoking status. This information confirms the lack of specificity of lung cancer symptoms and the fact that the absence of the most frequent symptoms (i.e., cough, pain, dyspnoea) should in no case lead to a decision to rule out the presence of this disease.
