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M.A. Gubens
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OA03 - Immunotherapy Checkpoint Inhibitors in Advanced NSCLC (ID 367)
- Event: WCLC 2016
- Type: Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
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OA03.07 - KEYNOTE-010: Durable Clinical Benefit in Patients with Previously Treated, PD-L1-Expressing NSCLC Who Completed Pembrolizumab (ID 6769)
12:05 - 12:15 | Author(s): M.A. Gubens
- Abstract
- Presentation
Background:
Checkpoint inhibitors such as the anti–PD-1 monoclonal antibody pembrolizumab have demonstrated antitumor activity and a manageable safety profile in several advanced malignancies. Although checkpoint inhibitors are rapidly becoming a standard-of-care therapy in multiple tumor types, the optimal treatment duration has not been established. We assessed outcomes in patients who completed the maximum 24 months of pembrolizumab in the phase 3 KEYNOTE-010 study (NCT01905657), in which pembrolizumab provided superior OS over docetaxel in patients with previously treated, PD-L1–expressing advanced NSCLC.
Methods:
1034 patients with advanced NSCLC that progressed after ≥2 cycles of platinum-based chemotherapy (and an appropriate therapy for targetable EGFR and ALK aberrations if present) and had a PD-L1 tumor proportion score ≥1% were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg Q3W or to docetaxel 75 mg/m[2] until disease progression, intolerable toxicity, or physician or patient decision; the maximum duration of pembrolizumab was 24 months of uninterrupted treatment or 35 cycles, whichever was later. Response was assessed per RECIST v1.1 by independent central review every 9 weeks. After completion of 24 months/35 cycles, patients continued to undergo imaging every 9 weeks; patients with subsequent disease progression were eligible for a second treatment course if they did not receive other anticancer therapy after stopping pembrolizumab.
Results:
In the overall population, median OS was longer (10.5 months for pembrolizumab Q2W, 13.4 months for pembrolizumab Q3W, and 8.6 months for docetaxel) and 24-month OS rates were higher (30.1%, 37.5%, and 14.5%, respectively) with pembrolizumab compared with docetaxel. Of the 691 patients allocated to pembrolizumab, 47 patients received 35 cycles of pembrolizumab and were included in this analysis. As of the September 30, 2016 data cutoff date, all patients had completed all 35 cycles of treatment, but one withdrew from the study treatment after completing 35 cycles. Best overall response (ORR) among these 47 patients was complete response (CR) in 3 (6%) patients and partial response (PR) in 39 (83%) patients, for an ORR of 89%; 5 (11%) patients experienced stable disease (SD). Two of these patients experienced disease progression since stopping pembrolizumab and two of these patients resumed pembrolizumab therapy. As of the cutoff date, none of the 47 patients had died.
Conclusion:
With long-term follow-up, the OS benefit has been maintained and pembrolizumab continues to demonstrate superiority over docetaxel. Pembrolizumab provides durable clinical benefit with few patients progressing after completing two years of therapy.
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OA19 - Translational Research in Early Stage NSCLC (ID 402)
- Event: WCLC 2016
- Type: Oral Session
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:G. Heller, G. Goss
- Coordinates: 12/07/2016, 11:00 - 12:30, Schubert 3
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OA19.06 - Adjuvant Chemotherapy Decisions Based on Molecular Risk Status Improves Outcomes in Early Stage, Non-Small Cell Lung Cancer (ID 5321)
11:55 - 12:05 | Author(s): M.A. Gubens
- Abstract
- Presentation
Background:
A clinically certified, 14-gene quantitative PCR expression assay has been found to assess mortality risk more accurately than clinicopathologic criteria in early-stage, non-squamous, non-small cell lung cancer (NSCLC). Clinically validated molecular stratification may provide a more informative approach to identify early stage NSCLC patients who are most likely to benefit from chemotherapy than current National Comprehensive Cancer Network (NCCN) high-risk clinicopathologic features.
Methods:
Prospective molecular risk-stratification by the 14-gene quantitative PCR expression assay was performed on 91 consecutive patients with stage I-IIA non-squamous NSCLC after complete surgical resection at a single institution. Information from molecular risk profiling was used in conjunction with pathologic stage and NCCN criteria to make adjuvant chemotherapy recommendations. Fisher’s exact test was used to compare recurrence rates, and Kaplan-Meier analysis and log-rank tests were used to evaluate differences in disease free survival.
Results:
Median age was 69 years, 57% were female and median follow up was 23±2 months. Among all patients, 33 (36%) met NCCN high-risk criteria for adjuvant chemotherapy and 27 (30%) were molecular high risk. Recommendations for adjuvant chemotherapy were discordant in 18 (55%) of NCCN high-risk patients and in 12 (44%) who were molecular high-risk. Twelve (44%) of molecular high-risk patients agreed to receive adjuvant chemotherapy. Whereas recurrence was observed in 33% of molecular high-risk patients who did not receive adjuvant chemotherapy, none of the molecular high-risk patients who underwent chemotherapy recurred (log-rank p=0.001).
Conclusion:
This prospective single-institution study demonstrates the clinical utility of molecular testing of early-stage NSCLC to supplement pathologic stage and NCCN guidelines in making adjuvant chemotherapy recommendations. Molecular risk scores better differentiated prospective recurrence rates than did NCCN risk criteria. This study provides preliminary evidence that molecular testing followed by adjuvant chemotherapy in molecularly high-risk patients may prevent a significant number of recurrences and improve outcomes.
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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-066 - Incorporation of a Molecular Prognostic Classifier Improves Conventional Non-Small Cell Lung Cancer TNM Staging (ID 5831)
14:30 - 14:30 | Author(s): M.A. Gubens
- Abstract
Background:
Tumor size, nodal spread, and distant metastases form the basis of current non-small cell lung cancer staging. Despite undergoing a major revision in 2009, the poor outcomes of early-stage lung cancer patients relative to other solid tumors such as breast and colorectal cancer suggests that further improvement to our ability to stage non-small cell lung cancers is needed. In this study, we demonstrate the benefit of integrating a clinically validated molecular prognostic signature into conventional TNM staging.
Methods:
A new staging system integrating a 14-gene molecular prognostic classifier with TNM descriptors was developed using 332 patients with stage I-IIIB non-squamous, non-small cell lung cancer resected at the University of California, San Francisco. This staging system was subsequently validated on a separate multi-institutional international cohort of 1379 patients with stage I-IIIB disease. Reclassification measures were used to assess for improvements in calibration and discrimination beyond conventional TNM staging.
Results:
In the validation cohort, 78.2% of patients were reclassified using the new staging system. 73% of these patients were reclassified more accurately. The new staging system demonstrated improved measures of model fit including the modified Nagelkerke’s R[2] statistic as well as the c-index. In addition, incorporation of the molecular classifier resulted in a Net Reclassification Improvement of 16.6% (95%CI 7.9-25.2%) and a relative Integrated Discrimination Improvement of 27.9% (95%CI 6.4-49.4%). Kaplan-Meier analysis of overall survival after surgical resection demonstrated superior survival curve separation with the addition of the molecular classifier. Figure 1. Kaplan-Meier analysis of overall survival from time of surgical resection (A: TNM staging, B: TNMB staging). Figure 1
Conclusion:
Incorporation of a molecular classifier of tumor biology offers substantial improvements to conventional TNM staging and encourages application of molecular prognostic classifiers into the refinement of TNM staging systems for other solid tumors.
