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R. Hui
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OA 10 - Liquid Biopsy for Genomic Alterations (ID 678)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Adrian G. Sacher, Pasi A Jänne
- Coordinates: 10/18/2017, 11:00 - 12:30, F201 + F202 (Annex Hall)
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OA 10.04 - Discussant - OA 10.01, OA 10.02, OA 10.03 (ID 10806)
11:30 - 11:45 | Presenting Author(s): R. Hui
- Abstract
- Presentation
Abstract not provided
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OA 17 - Immunotherapy II (ID 683)
- Event: WCLC 2017
- Type: Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Yuichiro Ohe, Anne Tsao
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 301 + 302
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OA 17.06 - Updated Analysis of KEYNOTE-024: Pembrolizumab vs Platinum-Based Chemotherapy for Advanced NSCLC With PD-L1 TPS ≥50% (ID 9582)
15:25 - 15:35 | Author(s): R. Hui
- Abstract
- Presentation
Background:
KEYNOTE-024 (ClinicalTrials.gov, NCT02142738) is a multicenter, international, phase 3, randomized, open-label, controlled trial of treatment with the anti‒PD-1 antibody pembrolizumab vs platinum-based chemotherapy as first-line therapy for patients with advanced NSCLC of any histology with PD-L1 tumor proportion score (TPS) ≥50% and without EGFR mutations or ALK translocations. Results from the primary analysis of KEYNOTE-024 demonstrated that after a median follow-up of 11.2 months, pembrolizumab significantly improved PFS (HR=0.50; P<0.001) and OS (HR=0.60; P=0.005) and was associated with a lower rate of treatment-related AEs compared with chemotherapy.
Method:
Patients were randomly assigned to receive either 35 cycles of pembrolizumab 200 mg every 3 weeks or 4–6 cycles of investigator's choice of carboplatin/cisplatin + gemcitabine, carboplatin + paclitaxel, or carboplatin/cisplatin + pemetrexed with optional pemetrexed maintenance (for those with non-squamous histology). Randomization was stratified by ECOG performance status (0 vs 1), histology (squamous vs nonsquamous), and geographic region (East Asia vs non–East Asia). Treatment continued until disease progression per RECIST version 1.1, intolerable toxicity, or withdrawal of consent. Patients in the chemotherapy arm who experienced disease progression could cross over to receive pembrolizumab monotherapy. Response was assessed every 9 weeks by blinded independent central review per RECIST version 1.1. The primary endpoint was PFS; secondary endpoints were OS, ORR, and safety.
Result:
305 patients were enrolled (pembrolizumab, n=154; chemotherapy, n=151). At the time of data cutoff (July 10, 2017) after a median follow-up of 25.2 months, 73 patients (47.4%) in the pembrolizumab arm and 96 patients (63.6%) in the chemotherapy arm had died. The hazard ratio for OS was 0.63 (95% CI, 0.47–0.86; nominal P=0.002). Median (95% CI) OS was 30.0 (18.3–not reached) months in the pembrolizumab arm and 14.2 (9.8–19.0) months in the chemotherapy arm. The Kaplan-Meier estimate of OS at 12 months was 70.3% (95% CI, 62.3%–76.9%) for the pembrolizumab group and 54.8% (95% CI, 46.4%–62.4%) for the chemotherapy group. 82 patients allocated to the chemotherapy arm crossed over to receive pembrolizumab upon meeting eligibility criteria. Treatment-related adverse events were less frequent in the pembrolizumab arm than in the chemotherapy arm (76.6% versus 90.0%, respectively) as were treatment-related grade 3-5 adverse events (31.2% versus 53.3%).
Conclusion:
With more than half of patients having OS events and prolonged follow‒up, first-line pembrolizumab monotherapy remains superior to platinum-based chemotherapy despite the crossover from the control arm to an anti-PD1 inhibitor as subsequent therapy.
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P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.07-018 - A Meta-Analysis of PD-L1 Expression as a Biomarker of PD-1 Blockade in Advanced Non Small Cell Lung Cancer (ID 9225)
09:30 - 09:30 | Author(s): R. Hui
- Abstract
Background:
The recognition of programmed cell death 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) as key therapeutic targets has led to the clinical development of several PD-1 and PD-L1 inhibitors as breakthrough treatments in advanced non small cell lung cancer. Although some patients experience durable tumour response, many do not derive any clinical benefit, therefore highlighting the importance of identifying methods to improve patient selection. PD-L1 expression on tumour cells with or without immune cells is the most reported association with anti-tumour activity of PD-1 blockade. Despite multiple publications, the use of different assays and cutpoints make it difficult to know if PD-L1 is a reliable biomarker for predicting outcomes to anti PD-1/PD-L1 treatment.
Method:
We performed a systematic search of MEDLINE, EMBASE, PubMed and conference proceedings up to 20 June 2017 and identified all clinical trials of anti PD-1 or PD-L1 monotherapy in advanced non-small cell lung cancer. We retrieved data regarding outcomes of 1 year overall survival (1yr OS), 1 year progression free survival (1yr PFS) and overall response rate (ORR), including 95% confidence intervals, in subgroups of varying PD-L1 tumour expression with cutpoints of 1%, 5%, 10%, 25%, 50% and 90%. Results were pooled and analysed based on different cutpoints. As PD-L1 expression is a continuum, we also tested for a correlation between outcomes and increasing cut-points of PD-L1 expression.
Result:
Of sixteen included studies with a total of 4,452 patients who received PD-1/PD-L1 inhibitor monotherapy, eight trials (n=821) reported on PD-1 blockade as first-line (1L) therapy and thirteen trials (n= 3,631) reported on treatment as second-line or beyond (>2L). Using 1% cutpoint, PD-L1 positivity was associated with higher ORR in 1L and >2L and 1yr PFS in >2L. Using a high cutpoint of 50%, PD-L1 positivity was associated with higher ORR in 1L and >2L, and higher PFS in 1L. Comparison of increasing cutpoints of PD-L1 expression and outcomes showed a positive correlation with 1yr PFS in 1L, a modest correlation with 1yr PFS in >2L and ORR in 1L and >2L, and little correlation with 1yr OS in 1L and >2L. Sensitivity analysis revealed no difference when excluding studies using the SP142 assay with weaker tumour staining.
Conclusion:
Within the limitations of current data, there is a positive correlation between increasing cutpoints of PD-L1 expression and ORR and 1yr PFS, but little correlation with 1yr OS in treatment naive and pretreated patients.
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PL 02 - Presidential Symposium including Top 3 Abstracts and James Cox Lectureship Award Presentation (ID 585)
- Event: WCLC 2017
- Type: Plenary Session
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:Hisao Asamura, Keunchil Park
- Coordinates: 10/17/2017, 08:15 - 09:45, Plenary Hall (Exhibit Hall D)
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PL 02.02 - Patient-Reported Outcomes with Durvalumab after Chemoradiation in Locally Advanced, Unresectable NSCLC: Data from PACIFIC (ID 10762)
08:20 - 08:30 | Presenting Author(s): R. Hui
- Abstract
- Presentation
Background:
Durvalumab, an engineered human IgG1 anti-PD-L1 mAb, demonstrated an improvement in PFS vs placebo and favorable benefit/risk profile in the Phase 3 PACIFIC study in locally advanced, unresectable NSCLC. Here we summarize patient-reported outcomes from PACIFIC.
Method:
In the randomized, double-blind, Phase 3 PACIFIC study (NCT02125461), patients who had previously received ≥2 cycles of platinum-based concurrent chemotherapy with definitive dose radiation without disease progression were randomized (2:1) to durvalumab 10 mg/kg i.v. q2w or placebo for up to 12 months. Secondary endpoints included evaluation of symptoms, function and global health status/QoL using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 v3 questionnaire and its lung cancer module, QLQ-LC13. Patients completed the questionnaires at baseline, Week 4, Week 8, q8w until Week 48, then q12w until disease progression. Changes from baseline for key symptoms were analyzed using a mixed model for repeated measures (MMRM). Time to deterioration (TTD) and odds of improvement were analyzed. Deterioration or improvement was defined as a change in score from baseline ≥10. Hazard ratios (HR) were calculated using a stratified log-rank test and odds ratios (OR) using logistic regression.
Result:
Compliance with completing the questionnaires was high in both durvalumab (n=476) and placebo (n=237) groups (>80% up to Week 48). There were no differences between groups at baseline in symptoms, function or global health status/QoL. MMRM analysis showed no statistically significant differences between treatment groups in adjusted mean changes from baseline (average over 12 months) in the prespecified symptoms of dyspnea, cough, chest pain, fatigue and appetite loss, and for global health status/QoL and physical functioning. Clinically relevant improvements from baseline were observed throughout the study in both durvalumab and placebo groups for dysphagia (mean [SD] change at Week 48, −14.2 [26.1] and −14.8 [25.3], respectively) and alopecia (−22.1 [33.0] and −21.4 [29.5]). There were no differences in median TTD between groups except ‘other pain’ (9.2 months with durvalumab vs 5.6 months with placebo [HR 0.72; 95%CI 0.58, 0.89]). The only difference in improvement rates between groups was for appetite loss (26.1% improvement rate with durvalumab vs 24.9% with placebo [OR 1.72; 95%CI 1.04, 2.85]). Other symptoms, function and health-related QoL remained stable throughout with no between-group differences in TTD or improvement rates.
Conclusion:
Durvalumab treatment did not worsen symptoms, function or health-related QoL. Clinically relevant improvement in alopecia and dysphagia with durvalumab and placebo was likely due to resolution of toxicities related to prior chemoradiation.
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