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valeria Cetoretta
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-15 - Association Between Opioids and Outcome of 1st Line Immunotherapy in Advanced NSCLC Patients: A Retrospective Evaluation (Now Available) (ID 2428)
10:15 - 18:15 | Author(s): valeria Cetoretta
- Abstract
Background
Opioids represent the pharmacological backbone of cancer-related pain treatment. However, preclinical studies suggest that opioids can cause immunosuppression. Recently, immune checkpoint inhibitors (ICIs) have become available for treatment of patients with advanced NSCLC. With this study we aimed at retrospectively evaluate the impact of chronic opioid treatment on the outcome of advanced NSCLC (aNSCLC) patients treated with first-line ICIs.
Method
We retrospectively reviewed the records of aNSCLC patients treated with anti-programmed-death-1 (PD-1) or its ligand (PD-L1) single-agent ICIs in 2 Italian institutions. We included all patients with enough follow-up to have at least one radiological evaluation during ICIs treatment. Patients with rapid clinical progression were included in the analysis. We analyzed response rate (RR), progression-free survival (PFS), and overall survival (OS). Response was evaluated using RECIST v1.1 criteria.
Result
75 patients were found, 64 included in the analysis. Mean age at diagnosis was 66.5 years (range 37-84), 65% were male. Histological type were: 76.5% adenocarcinoma, 14% squamous, 9.5% others, most with high PD-L1 expression (90.5% with ≥50% TPS). 58 patients (90.6%) were stage IV at ICIs start, with mean number of metastatic sites 1.8. Most patients were current/former smokers (87.5%); ECOG performance status (PS) at ICI start was: 0 in 34 pts (53.1%), 1 in 25 (39%), 2 in 5 (7.9%). 20 patients were receiving opioids at ICIs start (31.3%), with a mean daily dose equal to 59 mg of oral controlled-release morphine. With a median follow-up of 10.9 months, the median number of ICIs cycles was 7.5 (range 1-26). RR, mPFS and mOS in the whole series were 40.6%, 9.4 months and 17.1 months, respectively. Compared to the others, patients receiving opioids had numerically lower RR (30% vs 45.5%, p=0.24), a shorter PFS (median 12.7 vs 1.7 months, Hazard Ratio [HR] 4.16, 95%CI 2.15-8.05, p<0.001) and OS (median not reached vs 3.2 months, HR 4.68, 95%CI 2.09-10.52, p<0.001). At the multivariate analysis, opioid use continued to be significantly associated with worst PFS (HR 3.19, 95%CI 1.45-7.01, p=0.004) and OS (HR 4.16, 95%CI 1.61-10.76, p=0.003), even when accounting for PS, disease stage and number of metastatic sites.
Conclusion
Our results suggest a possible detrimental effect of opioids in aNSCLC patients treated with first line single-agent ICIs, even when correcting for other prognostic factors. However, due to the short follow-up, the small number of patients, and the lack of a control group, our results should be considered exploratory.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-17 - Correlation Between Clinic-Pathological Data and T790M Detection in EGFR Mutated NSCLC Patients Progressing on 1st/2nd Generation TKIs (Now Available) (ID 2442)
10:15 - 18:15 | Author(s): valeria Cetoretta
- Abstract
Background
Despite osimertinib is moving to the first-line for advanced NSCLC harboring EGFR activating mutations, some patients still receive a frontline first- or second-generation EGFR-TKI. In this setting, factors predicting the emergence of T790M resistance mutation at progression (PD) are lacking. The aim of this retrospective study was to investigate the correlations between clinic-pathological features and T790M positivity (T790M+) in a single-center cohort of EGFR mutated stage IV or recurrent NSCLC patients, who underwent liquid (LB) or tissue biopsy (TB) at PD when treated with first- or second-generation EGFR-TKIs.
Method
Data from 122 patients (80 female, 42 male) treated between 2012 and 2019 were considered for the analysis. EGFR mutations were detected with real time-polymerase chain reaction (RT-PCR) on LB and pyrosequencing or next generation sequencing on TB. PD was determined by RECIST 1.1 criteria. Univariate analysis by Fisher exact test was performed to assess any association.
Result
At diagnosis, 117 patients carried common EGFR mutations (84 exon 19 deletions; 33 exon 21 mutations), 5 had rare mutations (3 exon 18 mutations; 2 exon 20 mutations other than T790M) . At PD, 29 patients (24%) underwent only LB, 29 only TB (24%), 64 both (52%). The overall T790M+ rate was 67% (82/122). T790M+ was significantly higher among patients with exon 19 deletion than in those with exon 21 mutation (77% vs 51%, p=0.008). T790M+ was significantly more frequent in patients with exclusively intrathoracic PD as compared to extrathoracic PD (81% vs 56%, p=0.007). Patients with pleural involvement (PI), considered as pleural effusion or/and pleural disease, as site of PD (n=45) had a significantly higher frequency of T790M+ than those with stable or absent PI (n=77) (82% vs 58%, p=0.009), irrespectively of the pattern of PD. No correlation with other sites of PD was found.
Conclusion
Exon 19 deletion, intrathoracic PD and PI as site of PD are significantly associated with higher frequency of T790M+ in patients progressing to first-or second-generationEGFR-TKIs. These results, if confirmed by an independent validation cohort, may allow the development of a T790M+ predictive score accounting for type of mutation and sites of progression.
