Virtual Library
Start Your Search
S. Lan
Author of
-
+
P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.03a-058 - Is There a Place for Pemetrexed Rechallenge in Advanced Lung Adenocarcinoma? (ID 4537)
14:30 - 14:30 | Author(s): S. Lan
- Abstract
Background:
There is a lot of lung cancer patients progressing beyond the third or fourth line of treatment still suitable for further therapy .And some patients choose to receive previous chemotherapy rechallenge,particularly in patients who had previously responded.So the role of chemotherapy rechallenge is worth discussing.Pemetrexed is known to be a potent chemotherapeutic agent with high efficacy and low toxicity in the treatment of advanced lung adenocarcinoma.In clinical practice,it is used to rechallenge by certain patients,according to previous efficacy and tolerance, as long as it was stopped for reasons other than progression. Therefore, the aim of this retrospective study is to evaluate the efficacy and safety of pemetrexed rechallenge strategy in lung adenocarcinoma.
Methods:
We retrospectively identified patients with the following criteria:(i) clinical benefit (stable disease(SD) or partial response(PR)) from previous line of pemetrexed-based chemotherapy (ii) discontinuation for a reason other than progression (iii) rechallenge with pemetrexed after a minimal pemetrexed-based chemotherapy-free interval of 3 months.The main objectives were to evaluate disease control rate (DCR),progression-free survival (PFS), overall survival (OS) and toxicity of pemetrexed rechallenge .
Results:
62 patients were enrolled into this study. Initial pemetrexed-based therapy was used as 1[st] or 2[nd] line of chemotherapy in 46(74.2%), and 16(25.8%)of cases. 43(69.4%) patients achieved SD, 19 (30.6%) achieved PR. Pemetrexed was rechallenged as a 2nd, 3rd,or further line of chemotherapy in 43.5%, 37.1% and 19.4% of cases.4 patients (6.5%) achieved PR ,41 (66.1%) achieved SD and 17 (27.4%) experienced progressive disease.The median PFS was 3.9 months with the pemetrexed rechallenge.The median OS from the beginning of pemetrexed rechallenge was 8.2 months (95% CI: 5.0-11.3months).38(61.3%) patients had chance to receive further therapy after pemetrexed challenge failure.Next,we associated DCR,PFS,OS of pemetrexed rechallenge with the cllicial outcomes of initial pemetrexed treatment. We found that patients who had longer PFS (P=0.036)or achieved PR response(P=0.022) to initial pemetrexed were more likely to get benefit from rechallenge.The patients with longer PFS of initial treatment exhibited longer PFS of rechallenge (P=0.008). However, the interval time between initial and rechallenge treatment did not affect efficacy of pemetrexed rechallenge.25 patients (40%) reported grade 1/2 toxicity, 4 patients (6%) experienced grade3/4 toxicity, mostly neutropenia (65%) and hepatobiliary disorder (24%).
Conclusion:
It is a pragmatic strategy to retreat patients with pemetrexed when this drug has shown previous activity.The rechallenge treatment is generally well tolerated.
-
+
P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02b-031 - T790M: A Favorable Mutation? (ID 5681)
14:30 - 14:30 | Author(s): S. Lan
- Abstract
Background:
Patients with lung adenocarcinoma harboring somatic activating mutations in the epidermal growth factor receptor (EGFR) gene have benefited significantly from EGFR tyrosine kinase inhibitors (TKIs). However, a vast majority would eventually develop resistance to such TKIs, resulting in disease progression. T790M, a secondary mutation in exon 20 of the EGFR gene, has been identified as the major mechanism responsible for acquired EGFR-TKI resistance, accounting for roughly 50% of resistance. However, the association of T790M status and clinical outcome remains elusive. Here, we conducted a retrospective study examining the association between T790M status and prognosis on clinical samples obtained from 43patietns with EGFR-mutant lung adenocarcinoma and later acquired resistance to EGFR-TKIs.
Methods:
We performed capture-based targeted ultra-deep sequencing on either tumor biopsies or blood samples of 43 lung adenocarcinoma patients, who harbored EGFR mutations, and subsequently developed resistance to EGFR TKIs. We used BurningRock Biotech’s panels, consisting of critical exons and introns, covering multiple classes of somatic mutations, including single nucleotide variation (SNVs), rearrangements, copy number variations (CNVs) and insertions and deletions (INDELs) to detect genetic alterations both qualitatively and quantitatively.
Results:
We investigated the mutation spectrum after the development of resistance to EGFR-TKIs. Our analysis revealed 64% (18/28) of patients, harboring exon 19 deletions at baseline, acquired T790M at the time of progression. In contrast, only 33% (5/15) of patients, harboring exon 21 L858R substitutions at baseline, acquired T790M, indicating T790M mutation is more commonly found in patients with exon 19 deletions (p=0.052). Next, we associated T790M status with cumulative EGFR-TKI exposure time, and found patients had longer TKI exposure are more likely to acquire T790M mutation. The median TKI exposure time for patients who eventually acquired T790M was 19.20m ±1.86. In contrast, the median exposure time for patients who never acquired T790M 12.20m±1.20m (P =0.017). Furthermore, we investigated the presence of T790M mutation with progression free survival (PFS). Our data revealed that 68% (15/22) of patients with PFS≥12 months acquired T790M mutation after TKI exposure. In contrast, among patients with PFS< 12 months, only 38% of them acquired T790M mutation (p=0.048).
Conclusion:
Patients who eventually acquired T790M mutation have longer cumulative TKI exposure and are associated with longer PFS before the emergence of drug resistance. In addition, we also discovered that patients harboring exon 19 deletions are more likely to develop T790M mutation. Therefore, T790M status can be used as a potential biomarker for prognosis.
