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Elizabeth Jimenez Alguilar



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    MA04 - Novel Approaches with IO (ID 900)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
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      MA04.05 - Outcomes in NSCLC Patients Treated with First-Line Pembrolizumab and a PD-L1 TPS of 50-74% vs 75-100% or 50-89% vs 90-100% (ID 14358)

      14:00 - 14:05  |  Author(s): Elizabeth Jimenez Alguilar

      • Abstract
      • Presentation
      • Slides

      Background

      Among patients with NSCLC and a PD-L1 tumor proportion score (TPS) ≥50%, the response rate to the PD-1 inhibitor pembrolizumab is ~45%. Whether certain subsets of patients with a PD-L1 TPS ≥50% are more likely to benefit from treatment with a PD-1 inhibitor is currently unknown. We compared outcomes among NSCLC patients treated with first-line pembrolizumab and different PD-L1 TPS groupings: 50-74% vs 75-100% or 50-89% vs 90-100%.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively analyzed patients who received commercial pembrolizumab as first-line treatment for NSCLC with a PD-L1 TPS of ≥50% from the Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, and Massachusetts General Hospital. Clinicopathologic characteristics and clinical outcomes were compared among patients with a PD-L1 TPS of 50-74% vs 75-100% or 50-89% vs 90-100%. Event-time distributions were estimated using Kaplan-Meier and compared with the log-rank test.

      4c3880bb027f159e801041b1021e88e8 Result

      172 patients were identified for inclusion in this study. In the entire cohort, the overall response rate (ORR) to pembrolizumab was 33.9%, median progression-free survival (mPFS) was 4.8 months, and median overall survival (mOS) was 20.6 months. Compared to patients with TPS 50-74% (N=68, 39.5%), patients with TPS 75-100% (N=104, 60.5%) had a significantly higher ORR (45.2% vs 20.6%, P=0.001), a significantly longer mPFS (5.3 vs 2.5 mo, HR=0.61 [95% CI: 0.41-0.90], P=0.008), and a trend towards improved mOS (33.6 vs 20.6 mo, HR=0.60 [95% CI: 0.34-1.04], P=0.056). Compared to patients with TPS 50-89% (N=99, 57.6%), patients with TPS 90-100% (N=73, 42.4%) had a significantly higher ORR (50.7% vs 24.2%, P<0.001), a significantly longer mPFS (6.4 vs 2.8 mo, HR=0.52 [95% CI: 0.36-0.76], P<0.001), and a significantly longer mOS (33.6 vs 18.0 mo, HR=0.46 [95% CI: 0.27-0.79], P=0.008). There were no significant differences in smoking history, histology, sex, and age between patients in each TPS cutoff group.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Among NSCLCs with a PD-L1 TPS ≥50% treated with first-line pembrolizumab, higher PD-L1 TPS levels above 75% and 90% are associated with improved clinical outcomes compared to NSCLCs with lower PD-L1 levels.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MA19 - Genomic Markers of IO Response (ID 922)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 201 BD
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      MA19.01 - Efficacy and Genomic Correlates of Response to Anti-PD1/PD-L1 Blockade in Non-Small Cell Lung Cancers Harboring Targetable Oncogenes (ID 12921)

      15:15 - 15:20  |  Author(s): Elizabeth Jimenez Alguilar

      • Abstract
      • Presentation
      • Slides

      Background

      Immune-checkpoint inhibitors (ICIs) are associated with improved outcomes in a subset of patients with advanced non-small cell lung cancer (NSCLC). NSCLCs with targetable oncogenes are thought to be less responsive to ICI therapy, possibly due to association with never smoking status and reduced tumor mutational burden (TMB), but this has not been comprehensively characterized. We evaluated the responsiveness of NSCLCs with targetable oncogenes to ICIs, and if mutation type or TMB influence response.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Clinicopathologic, radiographic response, and sequencing data for patients with advanced NSCLC treated with ICI therapy was acquired from two separate cohorts (DFCI Oncopanel, n=296; MSKCC MSK-IMPACT, n=202). Durable clinical benefit (DCB) was defined as responsive/stable disease > 6 months. Samples with activating mutations in EGFR, ALK, ROS, BRAF, MET, and RET were identified. TMB was calculated as the sum of nonsynonymous mutations divided by the coding region captured in each panel. Objective response rates (ORR), DCB, and TMB were compared in targetable oncogene positive (TOP) vs oncogene negative (TON) patients. TMB was considered within each cohort to avoid confounding for differences in NGS panel technique.

      4c3880bb027f159e801041b1021e88e8 Result

      Targetable oncogenes were identified in 16% (82/498) of patients; 44(9%) EGFR, 15(3%) MET exon 14 splice site mutated, 8(2%) BRAF V600E, 6(1%) ROS1 rearranged, 5(1%) ALK rearranged, and 4(1%) RET re-arranged. Response to ICIs was similar in TOP vs TON patients, with ORR of 18% and 20%, and median PFS of 2.7 vs 2.8 months in TOP vs TON patients respectively. Among TOP patients, response rates differed by mutation type; ORR rate was 11%(5/44) in EGFR mutated, 40%(6/15) in MET mutated, 25%(2/8) in BRAF mutated, 33%(2/6) in ROS1 rearranged, and 0% in RET and ALK rearranged cancers (0/4, 0/5 respectively). Compared to WT, TMB was lower in TOP tumors (OncoPanel median 9vs11, p=0.0064; IMPACT median 4vs8, p=2.25e-06). TMB did not correlate with objective response or DCB in TOP tumors when considered collectively or by mutation type (OncoPanel median TMB 10vs8 in DCB vs NDB, p=0.52; IMPACT median TMB 3vs5 in DCB vs NDB, p=0.31)(Mann-Whitney U for all).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Despite lower TMB in oncogene positive NSCLC, these patients still derive clinical benefit from ICIs. ICI responsiveness is likely mutation specific, and is most pronounced in MET and BRAF mutated cancers. Among targetable oncogene positive NSCLC, TMB did not distinguish benefit. Taken together, low TMB in the presence of oncogenic driver mutations should not preclude ICI therapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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