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Luis Enrique Chara
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MA10 - Considerations in Immunotherapy / Real World (ID 911)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 105
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MA10.01 - Antibiotic Use and PD-1 Inhibitors: Shorter Survival in Lung Cancer, Especially When Given Intravenously. Type of Infection Also Matters (ID 13542)
10:30 - 10:35 | Author(s): Luis Enrique Chara
- Abstract
- Presentation
Background
Some studies found that cancer patients treated with PD-1 immune checkpoint inhibitors (ICI) who receive antibiotics (ATB) had worse efficacy outcomes because ATB can dysregulate gut microbiota. AvaiIable data in NSCLC are contradictory. In addition it’s unknow whether route of administration, type of the ATB and reason for its use, can affect survival outcomes.
a9ded1e5ce5d75814730bb4caaf49419 Method
This is a multicenter retrospective study. We included consecutive patients with advanced non-small-cell lung cancer (NSCLC) treated with nivolumab or pembrolizumab in second line or beyond between March 2015 and April 2018, from 7 hospitals in Spain. The aim of the study was to evaluate if patients taking ATB 2 months before or within the first month after starting ICI had worse OS, and if OS was affected by the route of administration, type of ATB, and the reason for its use.
4c3880bb027f159e801041b1021e88e8 Result
168 patients were evaluated. Median age was 65 years (39-85). 134(79,8%) were male and 121 (72%) had PS>=1. Predominant histologies were adenocarcinoma (50%) and squamous-cell carcinoma (42,9%). 92,3% received nivolumab and 7,7% pembrolizumab. The median number of prior lines was 1 (1-5), median number of cycles 11 (1-68). Median follow: 6,3m. Most were current or former smokers (94,6%). Only 2,9% had driver mutations. PD-L1 was available in 25% (<1%: 36,6%; 1-49%: 39%; >=50%: 24,4%). Response rate (RR) was 30,4%. 47,9% received ATB, 30% of them intravenously and 70% orally. Median PFS and OS were 5,6 months (m) (95%CI, 3,9-7,3) and 11,4 m (95%CI, 9,4-13,5). Patients who received ATB had shorter OS (8,1m (95%CI, 3,6-12,5) vs 11,9m (95%CI 9,1-14,7); p=0,026) and PFS (5m (95%CI,3,1-6,9) vs 7,3m (95%CI,2-12);p=0,028). Those patients receiving ATB intravenously had shorter OS than orally (2,9m (95%CI, 1,6-4,1) vs 14,2m (95%CI, 7,9-20,6); p=0,0001) and shorter PFS (2,2m (95%CI,0,6-3,7) vs 5,9m (95%CI,3,9-8); p=0,001). Patients treated for a lower respiratory tract infection (LRTI) and urinary infection had significantly shorter OS (6m (95%CI2,2-9,7) vs 26m (95%CI, 7,9-44); p=0,006).
8eea62084ca7e541d918e823422bd82e Conclusion
Our results suggest that use of antibiotics (mainly intravenously) has a negative impact on survival outcomes in patients with pretreated advanced NSCLC receiving ICI. To our knowledge, this is the biggest retrospective study evaluating the impact of ATB on the efficacy of ICI in NSCLC patients and the first one evaluating route of administration of ATB. We also found worse outcomes when ATB were administered for low respiratory or urinary tract infection.
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-69 - Validation of the Lung Immune Prognostic Index (LIPI): Useful to Identify Resistance to PD-1 Checkpoint Inhibitors in Pretreated Lung Cancer (ID 14122)
16:45 - 18:00 | Author(s): Luis Enrique Chara
- Abstract
Background
Derived neutrophils/(leukocytes-neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitors´ (ICI) outcomes. A lung immune prognostic index (LIPI) that showed association with ICI outcomes was developed by Mezquita L et al. based on these 2 systemic inflammation indicators (dNLR <3 and LDH > upper limit of normal (ULN)), characterizing 3 prognostic groups: good, 0 factors; intermediate, 1 factor; poor, 2 factors.
a9ded1e5ce5d75814730bb4caaf49419 Method
This is a multicenter retrospective study with the aim to validate prognostic value of LIPI score in pretreated advanced-stage non-small-cell lung cancer (NSCLC) treated with ICI. We included consecutive patients treated with nivolumab or pembrolizumab between March 2015 and April 2018 from 7 medical centers in Spain. Investigators at each institution retrospectively reviewed patients´medical records. Pretreatment LIPI score was calculated for all subjects and the primary endpoint was correlation with OS.
4c3880bb027f159e801041b1021e88e8 Result
A total of 168 patients were included. Median age 65 years (39-85). 134(79,8%) were male and 121 (72%) were PS≦1. Predominant histologies were adenocarcinoma (50%), and squamous-cell carcinoma (42,9%). 92,3% were treated with nivolumab and 7,7% with pembrolizumab. Median number of prior lines was 1 (1-5). Median number of cycles: 11 (1-68). Most were current or former smokers (94,6%). Only 2,3% had EGFR mutations, and 0,6% ALK rearrangement. PD-L1 immunohistochemistry was only available in 25% of patients (<1%: 36,6%; 1-49%: 39%; >=50%: 24,4%). After calculating LIPI score, 56,4% were LIPI 0 (good prognosis), 38,5% LIPI 1 (intermediate prognosis), and 5,1% LIPI 2 (poor prognosis). Response rate (RR) was 30,4% and disease control rate (DCR) 52%. The median PFS and OS were 5,6 months (m) (3,9-7,3) and 11,4 m (9,4-13,5). Median OS for good, intermediate, and poor was 14m (95% CI, 11,2-16,7), 6,3m (95% CI, 0,6-12) and 1,8m (95% CI, 0-4,3), respectively (p=0,0001). LIPI showed correlation with OS in patients with known PD-L1 status and also in those with no information about it. PFS was also correlated (p=0,004) with LIPI score. A LIPI score of 2 was independently associated with poorer OS (HR 4,9; 95% CI, 2,18-11,1).
8eea62084ca7e541d918e823422bd82e Conclusion
Our results support the prognostic value of pretreatment LIPI score. dNLR >3 and LDH greater than ULN was correlated with worse outcomes for ICI, regardless of the knowledge of PD-L1 status. This is a useful tool, based on clinical criteria, that can help us in daily practice to identify which patients benefit from ICI.
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