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Safiya Subegdjo
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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): Safiya Subegdjo
- Abstract
- Presentation
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.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.04-02 - Early Plasma ctDNA Response Anticipates Clinical Response to First-Line Immunotherapy in Advanced NSCLC (ID 14240)
12:00 - 13:30 | Author(s): Safiya Subegdjo
- Abstract
Background
Shedding of circulating tumor DNA (ctDNA) into plasma can be an independent prognostic indicator in lung cancer, and changes in plasma ctDNA levels correlate with response to targeted therapy. We hypothesized that serial assessment of plasma ctDNA by next generation sequencing (NGS) would enable early detection of response to immunotherapy in NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with advanced NSCLC who received first-line treatment with pembrolizumab alone or in combination with platinum doublet chemotherapy at the Dana-Farber Cancer Institute were enrolled in this study. Plasma collected from patients prior to starting therapy and again at 3 and 3 weeks after starting therapy was analyzed by NGS using enhanced tagged-amplicon sequencing of hotspots and coding regions from 36 genes (InVisionSeq). The trends of the ctDNA allele frequency were correlated with radiographic responses to therapy.
4c3880bb027f159e801041b1021e88e8 Result
Serial plasma samples were collected on 21 patients with the following characteristics: 67% female, median age 62, 90% adenocarcinoma, 10% squamous cell carcinoma. Pembrolizumab was administered as monotherapy to 18 (86%) patients and in combination with platinum/pemetrexed in 3 (14%) patients for a median of 6 cycles. Among the 8 (38%) patients with no detectable ctDNA at baseline, 5 patients who maintained no detectable ctDNA during serial analyses responded to treatment, and 3 patients with emergence of ctDNA within the first 6 weeks of treatment initiation experienced progressive disease. In the 13 (62%) patients with detectable ctDNA at baseline, radiographic responses were preceded by earlier changes in ctDNA allele frequency. Six of 7 patients with >50% decreases in ctDNA allele fraction responded to treatment while 4 of 6 patients with progressive disease had increases in ctDNA within 6 weeks.
8eea62084ca7e541d918e823422bd82e Conclusion
In advanced NSCLC treated with first-line immunotherapy, rapid decreases and clearance of ctDNA correlated with clinical benefit, while increasing or newly detectable ctDNA was a harbinger of progressive disease. These results suggest a potential role for ctDNA as an early pharmacodynamic biomarker of response or resistance to immunotherapies.
6f8b794f3246b0c1e1780bb4d4d5dc53
