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Sacha I Rothschild
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Lunch & Poster Display session (ID 58)
- Event: ELCC 2019
- Type: Poster Display session
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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157P - Prognostic impact of the use of antibiotics in patients with advanced non-small cell lung cancer (NSCLC) receiving PD-(L)1 targeting monoclonal antibodies (ID 242)
12:30 - 13:00 | Author(s): Sacha I Rothschild
- Abstract
Background
Anti-PD-(L)1 monoclonal antibodies (mAb) have changed the therapeutic landscape in patients with advanced NSCLC, still 35-40% of these patients derive no benefit from anti-PD-(L)1 mAb. Antibiotics alter gut microbiota diversity and composition, and may affects antitumor immune responses following immune checkpoint inhibitors (ICI) in NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Methods
We retrospectively included 218 patients with advanced NSCLC receiving anti-PD-(L)1 mAb. Overall survival (OS) (primary endpoint), progression free survival (PFS) and radiological response was compared between patients who received antibiotics within 2 months prior to the start of immunotherapy (ATB+) and patients who did not (ATB-). Assuming a rate of antibiotic comedication of 20% of all patients included, the study had a power of 70% to detect a 35% OS improvement in ATB- patients.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Patients are well balanced with the exception of PD-L1 immunohistochemical expression that was more frequent in ATB+ compared to ATB- (30% vs. 19%, P = 0.05). ATB+ compared to ATB- was associated with a significantly shorter OS (median OS, 10.6 vs 29.9 months, HR 2.7, 95% CI 1.7-4.1, P < 0.001) and shorter PFS (median PFS 1.4 vs 5.8 months, HR 2.2, 95% CI 1.5-3.4, P < 0.001). In the adjusted model for OS, the following 4 parameters retained a statistically significant prognostic value : ATB+ vs. ATB- (HR 2.8, 95% CI 1.7-4.5, P < 0.001), ECOG performance score >1 vs. 0-1 (HR 2.3, 95% CI 1.4-3.7, P = 0.001), squamous-cell vs. Non squamous-cell histology (HR 2.1, 95% CI 1.4-3.2, P < 0.001) and no prior radiotherapy vs. prior radiotherapy (HR 1.7, 95% CI 1.2-2.6, P = 0.006). ATB+ compared to ATB- was significantly associated with an increased risk of progressive disease as best radiological response (73% vs 41%, P = 0.002).
fd69c5cf902969e6fb71d043085ddee6 Conclusions
Antibiotic treatment is associated with a reduced clinical benefit from therapy with anti-PD-(L)1 mAb. The negative prognostic value of antibiotics was independent from known prognostic factors. However, further investigation is required on the mechanism behind this observation, with emphasis on the role of the gut microbiota composition in the context of anticancer immune response.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
M. Joerger.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25 -
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161P - Tumor mutational burden assessed by a targeted NGS assay predicts clinical benefit from immune checkpoint inhibitors in non-small cell lung cancer (ID 556)
12:30 - 13:00 | Author(s): Sacha I Rothschild
- Abstract
Background
In non-small cell lung cancer (NSCLC) immune checkpoint inhibitors (ICIs) significantly improve progression-free survival (PFS) and objective response rate. Biomarkers capable of predicting response to ICIs are highly desired. Assessment of tumor mutational burden (TMB) by whole-exome sequencing has been associated with outcome in patients treated with ICIs. Recently, being more suited for clinical applications, targeted sequencing has also proven its ability to reliably assess TMB. Our study is the first to evaluate the predictive power of TMB measured through the Oncomine Tumor Mutational Load (TML - Thermo Fisher Scientific) assay in 64 NSCLC patients treated with ICIs.
a9ded1e5ce5d75814730bb4caaf49419 Methods
TMB was assessed retrospectively in patients with metastatic NSCLC exposed to ICIs. Clinical data (RECIST 1.1) were collected and patients were characterized as either having clinical benefit (CB = complete/partial response (CR/PR) or stable disease (SD)) or having no clinical benefit. TMB was assessed using the TML assay, covering 409 genes. Differences in TMB between responders and non-responders were examined using Mann-Whitney test.
20c51b5f4e9aeb5334c90ff072e6f928 Results
TMB assessed by the TML assay was significantly higher in patients with CB compared to patients with no CB (median TMB = 5.9 versus 8.4 mutations/Mb, Mann-Whitney p = 0.028). TMB predicts CB by receiver operating characteristic (ROC, AUC = 0.66). 67% of patients with high TMB (cutoff = 3rd tertile, TMB = 8.7) were responders (CB), compared to only 24% of patients with low TMB (cutoff = 1st tertile, TMB = 5). TMB-high patients were characterized by a significantly higher progression-free survival (PFS) compared to patients with low mutational load (log rank for trend, p = 0.024). Finally, the highest response rate was observed in PD-L1 positive samples with high tumor mutational load (73%), whereas the PD-L1 negative and TMB-low population consisted of only 11% responders.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
Our results show that the TML panel is an effective tool for patient stratification for ICI treatment. Since we observed the highest response rate in PD-L1 positive patients with a high mutational load, we believe that a combinatorial use of biomarkers will maximize the precision of patient selection.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
University Hospital Basel.
213f68309caaa4ccc14d5f99789640ad Funding
Bristol-Myers Squibb, Thermo Fisher Scientific.
682889d0a1d3b50267a69346a750433d Disclosure
P. Jermann: Bristol-Myers Squibb provides funding in the form of a research grant. Thermo Fisher Scientific provides next-generation sequencing reagents and access to analysis software and technical support. All other authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25
