Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

N. Katodritis



Author of

  • +

    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
    • +

      P2.06-049 - TTF1 negative status is a negative predictor of benefit to Erlotinib (E) in metastatic Non Small Cell Lung Cancer (NSCLC) (ID 3382)

      09:30 - 09:30  |  Author(s): N. Katodritis

      • Abstract

      Background
      Erlotinib (E) is currently indicated as first line therapy in patients with EGFR mutations, and as second and third line treatment for patients with advanced metastatic NSCLC. In Cyprus comprehensive EGFR testing started in January 2011. In this study we reviewed all the patients that received E between 2007-2010, without having undergone EGFR mutation testing, looking at predictive factors of response to E. In view of evidence suggesting that EGFR mutations are found in predominantly TTF1 +ve tumours, TTF1 status as well as clinical factors (i.e. adenocarcinoma histology, female sex and non smoking status) were assessed as potential predictive factors of response to E.

      Methods
      100 consecutive patients are included. 3 patients received this as 1[st] line, 49 patients as 2[nd] line and 48 patients as 3rd line and beyond. Previous treatments included gemcitabine platinum doublet as first line, and either pemetrexed or docetaxel as 2[nd] line therapy. Patients had regular Chest x-rays (every 2-3 cycles) and CT scans (every 3-4 cycles) and were assessed clinically on a monthly basis. Survival outcomes for both progression free survival (PFS) and overall survival (OS) were calculated with Kaplan Meier. Subset analyses using smoking status, sex, histology type and TTF1 and finally Cox regression was undertaken.

      Results
      40 female and 60 male were treated with E. Median age is 66 years (range 32-79). 45 patients were WHO performance status (PS) 0-1, 47 PS 2-3. For 8 patients PS was not recorded. Median progression-free survival (PFS) for all patients was 95 days (95% CI 68-118). Median overall survival (OS) from starting E was 144 days (95% CI 103-185). Toxicity was predominantly grade 0-2. Ten (10) patients had a partial response and 34 patients had stable disease. Subset analyses were undertaken based on smoking status, sex, histology type and TTF1. Univariate analysis for PFS using KM plots showed a statistically significant difference for sex, smoking and TTF1. On Cox regression only gender and TTF1 were statistically significant (0.007 and 0.006). There was a striking difference in median OS between patients with TTF1-ve tumours (33 days) and TTF1 +ve tumours (149 days). See table underneath.

      Median PFS (days) 95% CI (days) Log Rank Median OS (days) 95% CI (days) Log Rank
      All patients 95 68-118 ------- 144 103-185 -------
      Female 165 46-284 0.0137 236 45-427 0.1470
      Male 80 40-120 104 60-148
      < 10 Pack Yrs 203 149-257 0.0009 291 193-389 0.0034
      > 10 Pack Yrs 54 15-93 84 53-115
      TTF1 – ve 28 11-45 0.0002 33 28-38 0.0001
      TTF1 +ve 109 34-184 149 35-263

      Conclusion
      TTF1 is a better predictor of benefit to E than histology, sex and smoking status. The very low median PFS and OS for patients with TTF1 –ve tumours would suggest that such patients derive no benefit from E, hence TTF1-ve status acts as a negative predictor of benefit to E.

  • +

    P3.09 - Poster Session 3 - Combined Modality (ID 214)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
    • +

      P3.09-017 - Concurrent Chemoradiotherapy (ConCRT) using Cisplatin-Vinorelbine in Locally Advanced (LA) Non-small Cell Lung Cancer (NSCLC) (ID 3274)

      09:30 - 09:30  |  Author(s): N. Katodritis

      • Abstract

      Background
      ConCRT is considered to be the standard of care in LA NSCLC. We adopted ConCRT as our standard of care for appropriately selected patients since 2005. This is an analysis of a register of all patients consecutively assigned ConCRT since 2005 (in an intent to treat analysis).

      Methods
      From Feb 2005 to Feb 2013 we assigned ConCRT for 56 consecutive patients with LA NSCLC, who were deemed unresectable; this included T4/N3/ “bulky” N2 disease or locally recurrent disease after initial surgery. Patients had ECOG performance status (PS) 0-2 and were treated with Cisplatin 75mg/m2 d1 and Vinorelbine 30mg/m2 d1-8, 3-weekly during the induction chemotherapy phase (i.e. full doses for the first 1-2 cycles) whilst with the addition of radical RT delivered concurrently with subsequent chemotherapy cycles, Vinorelbine was reduced to 12.5mg/m2 d1-8. After ensuring acceptable toxicity with the first 11 patients treated, subsequent patients received Vinorelbine at 15mg/m2 d1-8 during ConCRT and the number of treatment cycles was escalated to a maximum of 6. Patients received definitive CRT (59.4-64.8 Gy) unless surgery was planned, in which case restaging evaluation for potentially resectable patients was performed at 45-50.4 Gy. PET staging was only available in a minority of these patients, since 2011.

      Results
      56 patients: 51 men and 5 women. Median age was 63 (43-81); PS 0-1 n=47, PS 2 n=9. Radiological stage IIIB n=34 (61%), IIIA n=16 (29%), IIB n=6 (11%). Histology, squamous n=31, adenocarcinoma n=13, unspecified/other NSCLC n=12. Treatment delivered: median 4 cycles of chemotherapy (range 1-6) delivered. 50 patients (89%) completed ConCRT. Radiological response rates: Objective responses n=34 (29 partial, 5 complete) yielding a response rate of 61%; stable disease (SD) n=7; progressive disease (PD) n=7; of the remaining 8 non-evaluable patients, 6 patients did not complete ConCRT, either due to toxicity/death or disease progression. 7/50 patients who received ConCRT underwent surgery (5 lobectomies, 2 pneumonectomies). 6 of these 7 patients had a complete pathologic response (pCR) and 1 a near pCR. Kaplan Meier survival figures: median progression-free survival (PFS) 12.2 months (95% C.I. 8.8-15.6) and median overall survival (OS) 17.2 months (95% C.I. 11.8-22.6). There were 2 toxic deaths from neutropenic sepsis. The incidence of grade 3-4 oesophagitis or pneumonitis was < 10% and manageable. Detailed toxicity data will be presented in the full publication.

      Conclusion
      This regimen has produced encouraging results in a patient cohort with predominantly IIIB disease and with a significant minority of poor PS=2 patients, with close to 90% being able to complete the treatment. The 17.2 month median OS achieved in this cohort is similar to that reported previously from larger randomized phase III studies of ConCRT. Finally 11% of patients had pathological pCR, whist it appears that about 35% patients treated with this regime can achieve long-term survival.