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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
OA03.05 - Analysis of Early Survival in Patients with Advanced Non-Squamous NSCLC Treated with Nivolumab vs Docetaxel in CheckMate 057 (Abstract under Embargo until December 5, 7:00 CET) (ID 4392)
11:00 - 12:30 | Author(s): M. Steins
Nivolumab significantly improved OS versus docetaxel in patients with previously treated advanced non-squamous NSCLC (CheckMate 057; NCT01673867). Kaplan−Meier OS curves for nivolumab and docetaxel crossed at ~7 months, suggesting non-proportional hazards between arms.
Post-hoc analyses were conducted to explore relationships between baseline patient/disease characteristics, including PD-L1 expression, and death within the first 3 months of treatment (3motx). Additionally, the association between PD-L1 expression level and magnitude of clinical benefit was explored.
During the first 3motx, risk of death (rDt) was numerically higher with nivolumab versus docetaxel (59 versus 44 deaths among 292 and 290 patients, respectively). Early deaths were most commonly attributed to disease progression (no treatment-related deaths occurred). At 3motx, 80% of nivolumab-treated patients (233/292) and 85% of docetaxel-treated patients (246/290) were alive. After 3motx, the rDt was consistently higher in the docetaxel arm. In univariate analyses, no single baseline factor, including PD-L1 expression, EGFR mutation, ECOG PS, or smoking status, reliably characterized the rDt within the first 3motx with nivolumab. Among patients alive >3 months, the OS HR (95% CI) favored nivolumab in the overall population (0.59 [0.47−0.74]) and PD-L1 non-expressors (PD-L1 expression <1%; 0.66 [0.45−0.97]). In a multivariate analysis, factors associated with higher rDt within the first 3motx on nivolumab versus docetaxel were ECOG PS=1, time since last treatment <3 months, and/or progressive disease as best response to prior treatment combined with lower or no PD-L1 expression. However, the majority of nivolumab-treated patients with these attributes (including PD-L1 non-expressors), did not die within the first 3motx and experienced subsequent benefit. PD-L1 expression was a continuum, ranging from 1 to 100%, with increasing expression associated with enhanced ORR/OS benefit from nivolumab.
In CheckMate 057, the benefit−risk profile of nivolumab versus docetaxel was favorable across the overall patient population. During the first 3motx, a small difference in the number of deaths (n=15) was observed; thereafter the OS rate consistently favored nivolumab (2-year OS was >2-fold higher with nivolumab versus docetaxel). Patients with poorer prognostic factors and/or more aggressive disease combined with lower or no PD-L1 expression appeared to be at higher rDt within the first 3motx on nivolumab versus docetaxel. With the exception of PD-L1 status, these are recognized prognostic factors. While PD-L1 expression may help inform individual treatment decisions, PD-L1 status alone is not considered an appropriate biomarker for nivolumab treatment selection in pre-treated advanced NSCLC, but rather should be considered in the context of other patient/disease characteristics.
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P2.05 - Poster Session with Presenters Present (ID 463)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
P2.05-025 - 9-Year Experience: Prophylactic Cranial Irradiation in Extensive Disease Small-Cell Lung Cancer (ID 4017)
14:30 - 15:45 | Author(s): M. Steins
~In 2007, a EORTC study demonstrated a beneficial impact on overall survival with the use of prophylactic cranial irradiation in extensive disease small cell lung cancer. Nevertheless, there is ongoing debate over the role of PCI as patients in this trial did not undergo imaging of the brain prior to treatment, and a recent Japanese randomized trial showed a detrimental effect of PCI on OS in patients with a negative pre-treatment brain MRI. 87% of our patients received brain imaging prior to PCI.~
We examined the medical records of 137 patients with extensive disease small cell lung cancer who initially responded to chemotherapy and received PCI between 2007 and 2015. The outcomes, including the development of brain metastases and OS following PCI were analyzed. Survival and correlations were calculated using log-rank, univariate, and multivariate Cox proportional hazards-ratio analyses.
Median OS after PCI was 12 months and the median nPFS after PCI was 19 months. There was no significant survival difference in patients who received an MRI prior to PCI compared to patients who received a contrast enhanced computer tomography (CT) (p=0.20). Univariate analysis for overall survival did not show a statistically significant effect for known cofactors. Figure 1 Figure: OS (A) and nPFS (B) in patients with ED SCLC treated with PCI. .
We present the 9-year clinical experience with PCI in ED SCLC patients from one of Europe’s largest Lung Cancer Centres. PCI leads to a nearly doubled median OS compared to the irradiation arm of the EORTC trial with a 2-months prolonged median OS compared to the irradiation arm of the Japanese trial. PCI should remain standard of care for all patients with SCLC who have a response to initial chemotherapy. Contrast enhanced brain MRI instead of CT for staging prior to PCI is recommended if possible.