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B. Hughes
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MA 19 - Mesothelioma: Bench to Bedside (ID 680)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:Dean A Fennell, Hedy Lee Kindler
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 315
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MA 19.03 - Nintedanib + Pemetrexed/Cisplatin in Malignant Pleural Mesothelioma (MPM): Phase II Biomarker Data from the LUME‑Meso Study (ID 8111)
11:10 - 11:15 | Author(s): B. Hughes
- Abstract
- Presentation
Background:
Nintedanib is a triple angiokinase inhibitor. LUME-Meso (NCT01907100) is a randomised, Phase II/III study of ≤6 cycles of nintedanib+pemetrexed/cisplatin versus placebo+pemetrexed/cisplatin, followed by nintedanib or placebo maintenance, in chemo-naïve patients with MPM. In Phase II results, nintedanib+pemetrexed/cisplatin improved progression-free survival (PFS) versus control (hazard ratio [HR]=0.54; p=0.010), with a trend for prolonged overall survival (OS; HR=0.77; p=0.319). Benefit was most pronounced in patients with epithelioid tumours. Since no pharmacodynamic/predictive biomarkers are validated for anti-angiogenic therapies, exploratory analyses were conducted to investigate potential associations of plasma-derived angiogenic factors and genomic markers with treatment outcome in the LUME-Meso Phase II epithelioid population.
Method:
Blood samples were collected at baseline and, for patients receiving maintenance, at monotherapy Cycle 3 (C3mono) and end of monotherapy (EoTmono). Analyses focused on 58 angiogenic factors (Human AngiogenesisMAP[®] panel, Myriad RBM) and single-nucleotide polymorphisms (SNPs) in genes implicated in mesothelioma and/or associated with response to anti-angiogenic therapies in other tumour types (VEGFR1, VEGFR3 and mesothelin). Associations of biomarkers with treatment effect were evaluated by Cox regression and tested for interaction with false discovery rate (FDR) adjustment. Adjusted mean changes in angiogenic factor levels were compared between arms by ANCOVA. Analyses were exploratory, limited by small sample size, and considered hypothesis generating.
Result:
Of 77 patients with epithelioid tumours, angiogenic factor and genomic data were available for 71 and 67 patients, respectively. PFS/OS benefit of nintedanib appeared potentially more pronounced in patients with baseline plasma endoglin level below the median. There were possible weak associations between major homozygous genotypes for two VEGFR3 SNPs (rs307821 G/G and rs307826 A/A), and OS benefit and between VEGFR1 SNP rs9582036 A/A genotype and PFS benefit. Biomarker treatment associations were limited by small subgroup size, especially for low-frequency SNPs, and interaction tests were not significant after FDR adjustment. Regarding pharmacodynamic effects, adjusted mean change in interleukin-8 levels with nintedanib was greater from baseline to C3mono and lower from C3mono until EoTmono, compared with placebo. Nintedanib showed lower adjusted mean changes versus placebo for VEGFR2 from baseline to C3mono, and for VEGFR2 and VEGFR3 from baseline to EoTmono.
Conclusion:
These analyses represent the first biomarker results for nintedanib-treated MPM. While there seemed to be signals for greater PFS and OS improvement in patients with low plasma endoglin and major homozygous VEGFR1/3 genotypes, no biomarkers showed clear significant association with treatment benefit. These findings warrant further evaluation in the Phase III study.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-032 - Outcomes of Nivolumab in Metastatic NSCLC Patients via the Access Program Across Multiple Tertiary Oncology Centres. (ID 9298)
09:30 - 09:30 | Author(s): B. Hughes
- Abstract
Background:
Immune checkpoint inhibitors are the standard of care for non-small cell lung cancer (NSCLC) patients following first line therapy. There is limited information available on the outcomes of patients receiving these therapies for NSCLC outside of a clinical trial.
Method:
We retrospectively collected data from patients who received Nivolumab for advanced NSCLC on the Bristol-Myers Squibb (BMS) Access Program across four tertiary oncology institutions in Brisbane, Australia, to analyse their outcomes in a real-world setting, and compare these outcomes to those in Phase III randomised clinical trials.
Result:
85 patients were enrolled to this Ethics Committee approved audit - 32 females (37.6%); 53 males (62.4%); 54, PS 0-1 (63.5%); 30, PS 2-3 (35.3%); median age 67 yrs (range 42-84). 84 patients were evaluable for progression. 20% (17/84) of patients had a radiological partial response (PR) during the course of their treatment, and an additional 22.4% (19/84) patients had stable disease (SD) as their best response. In PS 0-1, 24% (13/54) had a PR, compared with only 10% (3/30) in PS 2-3 patients. The overall median progression-free survival (PFS) was 1.8 months, being 2.7 months in PS 0-1 versus 1.2 months in PS 2-3 patients. Median overall survival (OS) was 5.9 months; 6.5 months in PS 0-1 versus 2.3 months in PS 2-3 patients. Median OS for adenocarcinoma was 6.2 months, versus 4.7 months for squamous cell carcinoma. At 12 months after initiation of nivolumab 34% of patients were alive; 44% PS 0-1 versus 16% PS 2-3 patients. Grade 3 or 4 treatment related adverse events were observed in 10% of patients. Analysis of the prognostic relevance of routine haematological and biochemical parameters is ongoing.
Conclusion:
Nivolumab has clinically significant long term benefits in the treatment of relapsed NSCLC with 12 month survival rates in keeping with clinical trials in PS 0-1 patients. The development of predictive biomarkers remains central to identifying those patients, particularly with poor performance, most likely to benefit from immune checkpoint inhibitors.
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P2.07-033 - Anti-PD1-Induced Rotator Cuff Injury: A Case Series (ID 9339)
09:30 - 09:30 | Author(s): B. Hughes
- Abstract
Background:
Immunotherapy is now part of the standard of care for the treatment of metastatic non-small cell lung cancer (NSCLC). Immune checkpoint blockers, including anti-PD1 and anti-PDL1 therapies are generally well tolerated, but pose a risk of immune-related toxicities. With 40-50% of patients surviving at 12 months post second-line nivolumab treatment, survivorship concerns such as quality of life need to start being considered in these patients. Immune-related musculoskeletal symptoms are often overlooked, but can result in significant morbidity for a patient.
Method:
We present a case series of four patients who developed significant anti-PD1-induced rotator cuff injury during treatment for either metastatic NSCLC or metastatic mesothelioma.
Result:
Three patients were given nivolumab for advanced NSCLC, and one patient was given pembrolizumab for metastatic epithelioid mesothelioma. The severity of rotator cuff injuries ranged from tendonitis and bursitis, to a full thickness rotator cuff tear. One patient had bilateral rotator cuff injuries. The symptoms began 6-12 weeks after commencing immune checkpoint anti-PD1 therapy and resulted in significant morbidity for the patients in terms of daily activities. All injuries were managed conservatively with a combination of steroid injections, anti-inflammatories and physiotherapy. Pembrolizumab was ceased in the mesothelioma patient after 6 cycles, and the musculoskeletal symptoms rapidly resolved. Two of the NSCLC patients ceased nivolumab due to progressive disease, at 5 months and 9 months respectively. The third NSCLC patient continues on nivolumab, with stable disease at 17 months. In the NSCLC patients who had continued on nivolumab despite musculoskeletal symptoms, the rotator cuff injuries settled over time with conservative management.
Conclusion:
Immune-related musculoskeletal symptoms are inadequately reported in clinical trials, but can result in significant morbidity for patients, and therefore may impact on their compliance with immune checkpoint blockade therapy. Increased vigilance and prompt management of this condition within the context of multi-disciplinary care may assist with symptom-control.
