Virtual Library
Start Your Search
Hao Sun
Author of
-
+
JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Track:
- Presentations: 1
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
-
+
JCSE01.23 - Specific TP53 Mutation Subtypes as Biomarker for Response to PD-1/L1 Blockade Immunotherapy in NSCLC (ID 3437)
07:00 - 11:15 | Presenting Author(s): Hao Sun
- Abstract
Abstract
Background
Although TP53 co-mutation with KRAS have been proved to have predictive value for response to PD-1/L1 blockades, not all TP53 mutations are equal in this context. TP53 subtypes as independent factors to predict the response to PD-1/L1 blockade have not yet reported.
Methods
We performed an integrated analysis on the multiple-dimensional data types including genomic and clinical data from cohorts of NSCLC public (240 from MSK database) and local databases (224 patient with PD-L1 IHC score, 1986 NSCLC with TMB data). Durable clinical benefit (DCB) was defined as partial response/stable disease that lasted more than 6 months.
Results
The presence of mutant TP53 was associated with longer median progression free survival (mPFS) in NSCLC taking PD-1/L1 blockade therapy compared with TP53 wild-type group in the MSK-cohort (4.3 vs2.6 months, P=0.0027, HR=0.6409, 95%CI, 0.49 to 0.88). TP53 frameshift seemed to predict longer mPFS (6.6 months, P=0.0159, HR= 0.41, 95%CI, 0.26 to 0.65) than TP53 wild-type, TP53 missense (mPFS=4.27 months, P=0.17) and TP53 nonsense status (mPFS=2.7 months, P=0.002).NSCLC with TP53 frameshift mutation had a 52.9% rate of DCB, which was higher than TP53 missense (34.4%) and nonsense (21.1%) group. Besides, in the MSK cohort, five of six patients with TP53 truncated mutation in proline-rich (PR) domain (residues 58--101) achieved DCB, and one patient achieved 5.5 months of PFS and did not progress. Fractions of PD-L1 low-positive (1% - 49%) and PD-L1 high-positive (≥50%) tumors between each TP53 mutation subtype and wild-type groups are analyzed based on local data. The TP53 mutation rate was significantly higher in NSCLC with PD-L1 score >50% (P=0.004). But NSCLC with TP53 frameshift showed lower fractions of PD-L1 high-positive (12.5%, 2/16) compared with TP53 missense group (27.5%, 33/120) and TP53 nonsense group (25.8%, 8/31). PD-L1 low-positive rate is also lower in TP53 frameshift group (25.0%, 4/16) than TP53 missense (30.8%, 37/120) and nonsense group (29.0%, 9/31). Among 1986 NSCLC patients with TMB data, each TP53 mutation subtype is associated with significantly higher TMB than TP53 wildtype, especially among NSCLC with TP53 truncated mutation in PR domain (median TMB= 9 mut/Mbs). But no significant difference was found between TP53 mutation subtypes in TMB.
Conclusion
Our study demonstrated heterogeneity among TP53 mutations in predicting the response to PD-1/L1 blockade therapy. TP53 frameshift mutation may contribute to better PD-1/L1 blockade therapy response beyond PD-1/L1 IHC status. And the truncated TP53 mutation in PR domain may contribute to DCB.
-
+
P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.14-31 - Lack of Association Between BIM Deletion Polymorphism and Clinical Efficacy of EGFR-TKIs in NSCLC Based on NGS (Now Available) (ID 2154)
09:45 - 18:00 | Author(s): Hao Sun
- Abstract
Background
BIM deletion polymorphisms are most common in Asian population, with an incidence of 12-16% in lung cancer patients with EGFR mutations. Previous studies showed BIM deletion polymorphisms could predict poor treatment response to EGFR-TKIs, owing to loss function in mediating apoptosis of tumor cells. Recently, available data on BIM is inconsistent on its predictive role and we don’t know if NGS could bring us something new.
Method
Data were pooled from clinical trial CTONG0901 and local database in our hospital (GLCI). 194 and 117 EGFR mutant patients with IIIB-IV NSCLC are enrolled for survival analysis in the two cohorts, respectively. BIM status of all these patients were confirmed by NGS. 28 patients have baseline NGS results with 168 genes panel.
Result
The incidence of BIM deletion polymorphism in patients with EGFR mutation was 11.3% (22/194) and 17.6% (26/148) in CTONG0901 and GLCI, respectively. In CTONG0901, median PFS of patients treated with erlotinib or gefitinib between BIM deletion polymorphism and BIM wild type is 10.47m versus 11.17m (P=0.59). Median OS is 20.5m versus 20.47m (P=0.82). In GLCI, median PFS between BIM deletion polymorphism and BIM wild type is 10.13m versus 12.87m (P=0.33). Median OS is 58.5m versus 54.97m (P=0.82). No survival differences on PFS and OS present in the two cohorts. 28 patients with baseline NGS were analyzed from two cohorts. Three patients with MET amplification, ALK rearrangement and PD-L1 expression (20%+++) are lower than median PFS (8.63m). Two patients with MET amplification are around median PFS.
Conclusion
In our study, BIM deletion polymorphism has no relationship with the efficacy of EGFR-TKIs in CTONG0901. The result is confirmed in our local database. Outcomes of NGS showed that combined molecular variations, such as MET amplification, ALK rearrangement and PD-L1 expression seems more important to the prediction of EGFR-TKIs on NSCLC patients.
