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Alejandro Rodríguez Festa
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EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.14-11 - Real-Life Data of Osimertinib in Pretreated Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR T790M Mutation (Now Available) (ID 697)
08:00 - 18:00 | Author(s): Alejandro Rodríguez Festa
- Abstract
Background
Several clinical trials have demonstrated the efficacy and safety of osimertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) harbouring EGFR T790M resistance mutation. However, clinical real-world data on patient characteristics and efficacy of the drug is limited.
Method
We reviewed the medical records of T790M mutation-positive lung cancer patients treated with osimertinib between May 2016 and February 2019 in our institution. We calculated progression-free survival (PFS) and overall survival (OS) from osimertinib initiation.
Result
The study included 22 patients with a mean age of 59.6 years. 59% (13/22) were female and 100% had adenocarcinoma histology. We had an unusual high frequency of tobacco use in our series as 40.9% (9/22) of our patients were smokers (3/22) o former-smokers (6/22), with a mean of 35 pack-year (sd, 28.5). 45.5% (10/22) had exon 21 L858R mutations, whereas 54.5% (12/22) harboured exon 19 deletions (19del). One patient simultaneously had an exón 19 deletion and exon 20 S768I mutation. Osimertinib was used in second, third and fourth line in 50% (11/22), 27% (6/22) and 23% (5/22) of patients, respectively.
All patients had liquid biopsy blood samples obtained prior to the start of the treatment, and T790M mutation could be detected in 86.4% (19/22), with a mean mutant-allele fraction of 4,11% (standard deviation 8.65, min 0, max 37.7). T790M was detected only in tissue in 2 patients and exclusively in cerebrospinal fluid in 1 of them.
At the time of starting osimertinib, patients had a median of 3 metastatic sites (min 1, max 6), being the most frequent locations the lung (73%), the bone (64%), the pleura (59%), the central nervous system (23%) and the peritoneum (14%).
Median follow-up duration was 10 months (IQR, 4.7-22.67). To the date, 63% (14/22) have experienced progression of the disease. Median PFS in our series was 8.9 (95% CI, 4.9-17.9 ) months, whereas median OS since osimertinib initiation was 18.2 (95% CI, 8.8-NE) months.
Regarding to toxicity, 12 patients referred adverse events, 82.6% of which were mild (G1), being the most frequent toxicities neutropenia (9%), diarrhoea (9%), hypertransaminasemia (9%) and asthenia (9%). Only 1 G3 event was recorded (asymptomatic hyperamilasemia).
Conclusion
The efficacy of osimertinib in real-world practice was similar the observed in clinical trials, with a favourable adverse effect profile. Liquid biopsy is an effective non-invasive method to assess the presence of the T790M resistance mutation prior to the start of osimertinib.
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-16 - Agreement Between Different Methodologies for Non-Invasive p.T790M and EGFR Sensitizing Mutation Testing (ID 1965)
10:15 - 18:15 | Author(s): Alejandro Rodríguez Festa
- Abstract
Background
Tyrosine kinase inhibitors (TKIs) are the current standard of care for patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, most patients progressed within 1 to 2 years. The EGFR p.T790M mutation is the most common resistance mechanism to first and second generation EGFR TKIs. The identification of p.T790M mutation is of considerable clinical relevance as osimertinib has demonstrated clinical efficacy in this setting. Guidelines recommend testing for the p.T790M mutation in blood at relapse to TKIs, and re-biopsy only in case of a negative result. Several blood based methodologies for detection of EGFR mutations have been developed in the recent years. However, the number of comparison studies between platforms is very limited.
Method
This is a multicenter, cross-sectional study (ClinicalTrials.gov Identifier: NCT03363139) performed by the Spanish Lung Cancer Group. Samples from 75 consecutive EGFR mutant NSCLC patients were collected at disease progression to first line TKI treatment. The presence of EGFR mutations in the cfDNA was evaluated in 39 samples by 7 methodologies, namely: Cobas® EGFR Mutation Test v2 (Roche Diagnostics), Therascreen EGFR Plasma RGQ PCR Kit (Qiagen), QuantStudio® 3D Digital PCR System (Thermofisher), a 5′-nuclease real-time PCR (TaqMan®) assay in presence of PNA, OncoBEAM EGFR (Sysmex Inostics), NGS with two different gene panels: Oncomine® (Thermofisher) and Lung Cancer Panel (Qiagen). The agreement between methodologies was assessed using the kappa coefficient (K) and its corresponding 95% confidence intervals (95% CI). For quantitative variables the concordance correlation coefficient (ccc) was used.
Result
Complete results are available for 39 patients. Overall, the agreement between all methodologies for the detection of p.T790M mutation as well as the original EGFR sensitizing mutation was good (K=0.669; 95CI: 0.504-0.835 and K=0.750 95CI: 0.599-0.899 respectively). Remarkably, the agreement between FDA-approved methodologies for p.T790M detection was almost perfect (K=0.926; 95CI: 0.712-1) and good for the EGFR sensitizing mutations (K=0.657; 95CI: 0.417-0.902). Similarly, the agreement between NGS-based methodologies for the detection of p.T790M and the EGFR activating mutations was very high (K=0.843; 95CI: 0.567-1 and K=0.872 95CI: 0.595-1 respectively). Moreover, concordance between both technologies for p.T790M and EGFR sensitizing mutation mutant allele frequency was excellent (ccc=0.956; 95CI: 0.906-1 and ccc=0.980 95CI: 0.950-1 respectively). The proportion of samples that were positive for p.T790M detection varied from 28% (PCR based technologies) to 37% depending on the methodology.
Conclusion
NGS and PCR-based methodologies show a good to excellent agreement for the detection of EGFR mutations, including the p.T790M. Our results support the use of liquid biopsies for non-invasive testing of clinically relevant mutations (Data from the whole cohort will be presented at the meeting).
