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Omer Fatih Olmez
P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 2
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
P1.14-01 - Are Pretreatment Inflammation-Based Prognostic Scores Useful in Predicting the Outcomes of Patients with ALK-Positive NSCLC? (ID 1439)
09:45 - 18:00 | Presenting Author(s): Omer Fatih Olmez
Approximately 5% of all diagnosed non-small cell lung cancer (NSCLC) patients harbor a genetic rearrangement between the ALK and EML4 genes, representing a specific molecular and clinical subgroup (ALK+ NSCLC). To date, upfront treatment with ALK-tyrosine-kinase inhibitors (ALK-TKIs) has replaced chemotherapy in the first line setting for this subset of patients with excellent results, but reliable prognostic markers are lacking. An increased systemic inflammatory response has been shown to be associated with a poor prognosis, and some of the parameters used to characterize this response can easily be measured in clinical practice in several tumor types, but have not been analyzed extensively in ALK+ lung cancer in the era of crizotinib.Method
We reviewed the medical records of all patients with previously treated advanced ALK-positive NSCLC who received crizotinib between January 2013 and March 2018 outside of a clinical trial. Pre-treatment modified Glasgow prognostic score (mGPS), Prognostic Nutritional Index (PNI) and Systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI and SII on overall survival (OS), progression-free survival (PFS), and overall response rate (ORR).Result
82 patients were treated. Median age was 52.5 years (range; 20–77 years); 42.7% were female. Eighty-four point two percent of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥1; 17.1% had received ≥2 prior systemic therapies. The objective response rate was 77.2% (CR+PR).The optimal cutoff levels were 0.09 for mGPS and PNI, 934.7 for SII by ROC curves analysis. Patients in the SII ≥ 934.7 grous was significantly correlated with worse PFS and OS by univariate analysis (Figure 1).In multivariate analyses, pretreatment prognostic nutritional index (PNI) ≥ 0.09 was independently associated with inferior OS (1 year OS rates, 90.2% vs. 73.7%; HR 2.46, 95% CI 0.88-4.85; p = 0.035). Additionally, we evaluated the effects of these markers on response prediction. The logistic regression analysis of the predictive factors for the response to crizotinib demonstrated that the mGPS and PNI were associated with inferior ORR (OR: 0.1, 95% CI 0.16-1.04; p = 0.009 and OR: 0.16, 95% CI 0.02-0.55; p = 0.035, respectively).
In a cohort of patients with ALK positive NSCLC treated with crizotinib in routine practice,elevated pre-treatment SII was associated with shorter OS and PFS in univariate analysisand PNI was associated with shorter OS in multivariate analyses. Moreover the mGPS and PNI were associated with lower response rates.
P1.14-15 - Lorlatinib in ALK- or ROS1-Positive Non-Small Cell Lung Cancer Patients: Experience from an Early Access Program in Turkey (ID 1971)
09:45 - 18:00 | Author(s): Omer Fatih Olmez
Lorlatinib, a third generation ALK and ROS1 inhibitor, is indicated for the treatment of patients with ALK+ metastatic NSCLC whose disease has progressed on crizotinib and at least one second-generation ALK inhibitor. The aim of this study is to evaluate the efficacy and safety of lorlatinib in an Expanded Access Program (EAP) in Turkey.Method
The EAP was open-label, multicenter, and single-arm. Patients were eligible to receive lorlatinib (100 mg p.o/day) if they had advanced stage ALK- or ROS1-positive NSCLC and had progressed on crizotinib and/or second generation ALK inhibitors such as ceritinib or alectinib. The primary endpoint was PFS with lorlatinib. Secondary endpoints were objective response rate, overall survival, and safety.Result
Between February 2017 and December 2018, a total of 91 patients were admitted to the EAP at 27 oncology centers in Turkey. Eleven patients died before receiving the drug. Four patients were excluded from the EAP because of lost of the follow-up. Of the 76 patients who received drug, 13 were excluded from the analysis due to inability to access patient information. Six of these 13 patients were on lorlatinib treatment at the time of data collection. The median age of patients was 53.5 (17-84) years. Of 63 evaluable patients, 55 (87.3%) had ALK+ NSCLC and 8 (12.7%) had ROS1+ NSCLC. All patients had adenocarcinoma histology, and 54% (n=34) had brain metastasis before lorlatinib treatment. Twenty-one patients received lorlatinib as third-line treatment (mostly after chemotherapy and crizotinib). Median follow-up was 9.1 months. Five patients died before the first evaluation of response. In patients who received at least 1 dose of lorlatinib, median PFS was 12.6 months, and 1-year PFS rate was 53%. In ALK+ patients, median PFS was 14.7 months and 1-year PFS rate was 55%. In ROS1+ patients, median PFS was 9.1 months and 1-year PFS rate was 47%. In patients who received only crizotinib prior to lorlatinib, median PFS was 14.8 months and 1-year PFS rate was 59%. In patients who received ≥2 ALK inhibitors prior to lorlatinib, median PFS was 5.1 months and 1-year PFS rate was 27%. One-year OS rate was 65%. In response-evaluable patients (n=55), the ORR and DCR were 68.6% and 87.0% all patients. However, ORR and DCR were 69.6% and 87.0% for ALK+ and 62.5% and 87.5% for ROS1+ patients. Of response-evaluable 55 patients, the frequency of brain metastasis before lorlatinib was 54.5% (n=30). In only 7 patients (12.7%), brain metastasis developed under lorlatinib treatment. CNS control rate with lorlatinib was 87.3%. Dose reduction occurred in 9 patients (14.3%). Reasons for discontinuation of treatment were disease progression (n=17, 26.8%), adverse events (n=2, 3.2%), death (n=13, 20.6%), and unknown reasons (n=13, 20.6%).Conclusion
In this EAP, lorlatinib showed systemic activity in patients with advanced ALK+ or ROS1+ NSCLC, regardless of CNS metastases and previous TKI treatment.
P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
P2.01-64 - Systemic Inflammatory Markers as a Predictors of Response to Crizotinib in Patients with ALK-Positive Non-Small-Cell Lung Cancer (ID 1131)
10:15 - 18:15 | Author(s): Omer Fatih Olmez
The significance of the presence of a systemic inflammatory response (SIR) in predicting survival has been demonstrated in patients with cancer. Moreover, neutrophil-to-lymphocyte ratio (NLR),lymphocyteratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) have been also investegated in patients with both early and advanced non-small-cell lung cancer (NSCLC). However, determination of SIR predicting outcomes of patients who are likely to response to crizotinib in ALK-positive NSCLC patients has not been clearly demonstrated. The aim of this study was to investigate the prognostic and predictive value of NLR, LMR and PLR in patients with ALK-positive NSCLC treated with crizotinib.Method
Eighty-two patients with ALK-positive NSCLC who were treated with crizotinib were retrospectively analyzed. The cutoff values for NLR, LMR and PLR were defined by the receiver operating characteristic (ROC) curve analysis.Univariate and multivariate analyses were used to evaluate the prognostic significance of NLR, LMR and PLR. Logistic regression analysis was also performed to determine predictive indicators of response to crizotinib.Result
Among 82 patients, 35 (42.7%) were male and 47 (57.3%) were female, with a median age of 52.5 years (range; 20–77 years). Crizotinib treatment was administered as a first-line in 26.8% of patients, second-line in 56.1%, third-line in 12.2% and forth-line and later in 4.9%. The objective response rate was 77.2% (CR+PR) and stable disease was obtained in 7.6% of patients. According to the ROC curve, the recommended cutoff values of NLR, LMR and PLR were 3.14, 2.31 and 185,5 respectively. The median follow-up time was 19.3 months. ECOG performance status (PS) (p=0.014) and response to crizotinib (p=0.001) for progression-free survival (PFS) and ECOG PS (p<0.001), response to crizotinib (p<0.001), NLR (p=0.029) and LMR (p=0.028) for overall survival (OS) were found to be prognostic factors by univariate analysis. On the other hand, multivariate analysis showed that only ECOG PS and response to crizotinib were independent prognostic indicators for both PFS and OS.A logistic regression analysis indicated that NLR and LMR was found to bean independent factor for predicting response to crizotinib (p=0.007, OR:0.10 and p=0.044, OR: 0.20, respectively).Conclusion
Our findings showed that NLR and LMR are readily feasible and simple and also inexpensive biomarkers predicting response of crizotinib for patients with ALK-positive advanced NSCLC.