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L. Falchero



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    O15 - NSCLC - Chemotherapy II (ID 109)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O15.03 - Phase III, randomized, multicenter study comparing in elderly patients (≥70 years) with stage IV non small-cell lung cancer (NSCLC) a standard strategy of treatment allocation (carboplatin based bi-therapy or monotherapy with docetaxel) based on performance status (PS) and age with an experimental strategy allocating the same chemotherapies or best supportive care (BSC) according to a comprehensive geriatric assessment (CGA) - Study ESOGIA-GFPC-GECP 08-02. (ID 694)

      10:50 - 11:00  |  Author(s): L. Falchero

      • Abstract
      • Presentation
      • Slides

      Background
      Incidence of advanced NSCLC in the elderly is increasing. The use of a CGA is recommended to detect the patient’s vulnerability but its integration in treatment decision making has never been prospectively evaluated. The main objective of this study was to show that, compared to a standard strategy based on PS and age, the use of a CGA can improve the management of NSCLC in first line.

      Methods
      Randomized, multicentric, prospective phase III study in patients ≥70 y, PS 0-2 with stage IV NSCLC. We compared in arm A a standard algorithm of chemotherapy allocation based on PS and age: carboplatin based doublet in PS≤1 and age ≤75y, mono-therapy in PS =2 or age >75y with in arm B an experimental strategy of treatment allocation based on CGA: carboplatin based doublet for fit patients, mono-therapy for vulnerable patients and BSC for frail patients. Carboplatin (AUC5,d1), was associated to pemetrexed (500 mg/m2,d1) in non-squamous tumors and to gemcitabine (1000 mg/m2, d1-8) in squamous tumors, monotherapy was docetaxel 38 mg/m2 (d1-8). Four cycles of chemotherapy were to be given every three weeks. The main endpoint was time to failure treatment (TTF=duration between the date of randomization and the date the patient was withdrawn from treatment for any reason (progression, toxicity, death), secondary endpoints were Overall Response Rate (ORR), overall survival (OS), toxicity and quality of life (QoL), survival adjusted on QoL .

      Results
      493 patients were randomized from 01/2010 to 01/2013 by 45 centers. Patients characteristics were: male: 74%, median age: 77 (70-91) years, non-squamous histology: 71.8%, PS 0-1: 81.4%, ADL<6:13.9%, IADL<4:27.5%, Charlson’s index ≥2: 23%, score GDS 5≥3:2.5%. The 2 arms were well-balanced for patients characteristics except for ADL<6 (17.4% in arm A vs 10.3% in arm B). Respectively in arms A and B, 34.4% and 47% patients received a carboplatin based doublet, 65.6% and 31.5% received docetaxel and in arm B 21.5% received BSC. There was no significant difference in terms of TTF, respectively for arm A and arm B: median TTF was 99 days (d), 95%CI:[89; 126] vs. 98 d, 95%CI:[81;135], p=0.7149 and in terms of mOS: 196 d in arm A, 95%CI [171;231] vs. 185 d in arm B ,95%CI [148;235], p=0.7784. All grades toxicities were significantly less frequent in arm B than in arm A (93% vs.86.2%, p=0.016), but there was no difference in terms of grade 3-4 toxicities. All the secondary endpoints data will be updated at time of the meeting.

      Conclusion
      this large phase III study failed to show a superiority of a CGA based strategy of treatment allocation in terms of TTF. In experimental arm, 21.5% of frail patients according to Balducci’s criteria were enrolled and received an exclusive BSC management. Carboplatin-based doublets with pemetrexed and gemcitabine according to histology are feasible with a good profile of tolerance in selected elderly patients. This study will help to precise the most relevant geriatric tools and their cut-off in order to improve the management of the elderly with advanced NSCLC.

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    P2.09 - Poster Session 2 - Combined Modality (ID 213)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P2.09-001 - Phase II study of concurrent chemo-radiotherapy (CRT) with weekly cisplatinum plus oral vinorelbine in fit elderly patients with nonresectable locally advanced non-small-cell lung cancer (NSCLC) assessed by Standardized Geriatric Assessment (RACCOSA, GFPC 08-06 study): interim analysis. (ID 233)

      09:30 - 09:30  |  Author(s): L. Falchero

      • Abstract

      Background
      Few studies are dedicated to elderly patients with unresectable stage IIIA/B. We used a Standardized Geriatric Assessment (SGA) to select fit elderly patients and assess if this population can benefit from standard of care, namely concurrent CRT.

      Methods
      The aim of this multicentric phase II opened-study was to assess CRT in patients older 70 years with locally advanced NSCLC, evaluated as “fit” according to SGA.CRT associated oral vinorelbine (30 mg/m²/week) and IV cisplatinum (30 mg/m²/week) during 6 weeks concurrently with radiotherapy (66 Gy, 33 fractions, 6,5 weeks). Main inclusion criterias were : PS ≤ 1, weight loss < 10%, creatinine clearance ³ 50 ml/mn abreviated, VEMS ³ 40%, PaO2 ³ 60 mm Hg, KCO ³ 60% and patient classified as fit according to SGA. The principal end-point was early treatment tolerance (number of patients with adverse event grade ³ 3 (except nausea and vomiting) or grade 4 for hematologic toxicity and asthenia. Secondary end-points were RECIST response 4 weeks after treatment, quality of life, tolerance, progression-free survival and overall survival. Using a Simon's optimal plan in 2 steps, the total number of patients to be included was 59 with an intermediate analysis after 19 patients. Toxicities and serious adverse events were monitored by an independent peer committee.

      Results
      Interim analysis was done after 23 inclusions in 19 evaluable patients: males 84% , mean age 74.6 (70 to 83) years, 3 patients didn’t end the treatment (1 disease progression, 1 cons-indication for radiotherapy, 1 patient choice). Four patients had adverse event ≥ 3 (except nausea and vomiting) or grade 4 hematologic toxicity and asthenia. Treatment efficacy was: 1 RC, 10 RP, 5 SD, 1 PD. Two patients were not evaluable (1 early death, 1 patient’s refusal to further treatment). The independent peer committee judged that toxicities were acceptable and consistent with what was expected. Study is ongoing with 44 enroled patients currently.

      Conclusion
      The interim analysis of a phase II study of CRT in fit elderly patients with no resecable locally advanced NSCLC assessed by SGA showed an acceptable toxicity. Results will be upgraded for the congress.

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    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.10-013 - Randomized non comparative multicenter phase II study of sequential erlotinib with docetaxel versus docetaxel alone in patients with non small cell lung cancer (NSCLC) after failure of first line chemotherapy (TARSEQ): a GFPC 10.02 study. (ID 972)

      09:30 - 09:30  |  Author(s): L. Falchero

      • Abstract

      Background
      Erlotinib and docetaxel are approved in second line treatment of advanced NSCLC. Concomitant administration of a tyrosine kinase inhibitor (TKi) of EGFR with standard chemotherapy in first line did not improve survival compared to chemotherapy alone. Preliminary studies support a possible efficacy of sequential administration of EGFR TKi and chemotherapy. Objective: This open randomized phase II trial (Tarseq) was designed to assess the efficacy and tolerability of second-line sequential erlotinib plus docetaxel in advanced NSCLC.

      Methods
      Patients were randomized (1/1, stratified by center, disease status: recurrent or refractory (no response observed after 4 cycles of first-line chemotherapy))between sequential erlotinib 150 mg/d (day 2-16) + docetaxel (75 mg /m2 d1- 21) (arm A) versus docetaxel (75mg/m2 d1) alone (arm B) until disease progression or unacceptable toxicity. Primary endpoint was the rate of patients with progression-free survival at 15 weeks (PFS15) ; second endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and tolerability. Main eligibility criteria were advanced NSCLC, EGFR wild type or unknown, performance status 0 to 2, failure of first line cisplatin based chemotherapy; main exclusion criteria were more than 2 lines of treatment, previous anti-EGFR or docetaxel treatment. Statistical analysis was based on a Simon’s optimal two stage design . The primary endpoint is rejected if the number of efficacy is less 33 over 66 pts (25+ 41) at the end of the two stages.

      Results
      147 patients were randomized by 33 centers: median age: 60 ± 8 years, PS 0/1/2 (44/83/20 pts) ; male: 78%, EGFR status: wild type 66%, unknown: 34%; recurrent patients: 65% (arms A/B :66%/65%), nonsquamous: 86% (arms A/B : 84%/90%), smoking status: smokers 35%, formers 57,5%, never 7,5%. Baseline characteristics were balanced between 2 arms. In ITT, the primary objective was not meet with 18/66 pts without progression at 15 weeks in arm A, 17 /66 pts in arm B. In arm A and B, median PFS was 2,2 (CI95% 1,6-2,8) and 2,5 (CI 95% 1,7-2,8) months and median OS was 6,6 (CI 95% 4,3-10,3) and 8,4 (CI 95% 4,5-11,3) months respectively. Toxicity was acceptable in both arms with 60.2 % and 54% of G3/4 toxicity in arms A and B, respectively.

      Conclusion
      The sequential combination of erlotinib with docetaxel did not demonstrate any benefit in second-line treatment of EGFR wild type or unknown advanced NSCLC, despite acceptable toxicity. The Pharmacological hypothesis of synergism between erlotinib given sequentially and standard chemotherapy is not confirmed in the present study. Clinical trial information: NCT01350817 / Supported by an academic grant from Roche, Chugai, Sanofi Aventis,with the help of clinical research direction ( Limoges University Hospital)

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    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P2.24-039 - Renal failure is the first cause of double maintenance (bevacizumab + pemetrexed) discontinuation for toxicity in real world setting (ID 2491)

      09:30 - 09:30  |  Author(s): L. Falchero

      • Abstract

      Background
      Maintenance treatment, with either bevacizumab or pemetrexed, has been shown to increase PFS and overall survival. Two trials have compared double maintenance (DM) therapy (pemetrexed + bevacizumab), to single drug maintenance (bevacizumab in AVAPERL and POINTBREAK studies). Conflicting results were found. Before definitive conclusions can be driven from these studies and other ongoing study (ECOG 5508), the purpose of our retrospective study was to determine in real world setting the frequency of double maintenance discontinuation for adverse event, and to describe the main toxicities occurring during double maintenance.

      Methods
      All patients who received at least one cycle of pemetrexed and bevacizumab as maintenance treatment were identified from the Oncology Pharmacy database of participating centers since year 2011. All the charts were analyzed retrospectively to obtain clinical data. Lab results were noted for haemoglobin, creatinine and liver enzymes before starting and after receiving multiple doses of pemetrexed and bevacizumab.

      Results
      Included were 87 patients treated with two to six cycles of induction chemotherapy (median 4), combining platinum with pemetrexed and bevacizumab, followed by at least one cycle of bevacizumab and pemetrexed as maintenance treatment. All patients received supplementation of vitamin B12 and folic acid during chemotherapy. Baselines characteristics (%): male 54: stage IV 96,5; adenocarcinoma 96,5; median age 58 yr. 57,8% of patients had objective response after induction chemotherapy, and 42,2% had stable disease after induction chemotherapy. At cut off date: treatment was still ongoing for 17 patients (19,8%); 40,6% of patients stopped DM for progressive disease; 33,3% of patients stopped DM for toxicity (out of these 33% of patients, 42% went on single maintenance with Pemetrexed and 58% with Bevacizumab); 11,6% of patients stopped DM for patient/physician decision, and 14,4% for other reasons. The most common toxicity responsible for DM discontinuation was renal failure (52%).

      Reason for discontinuation (%) POINTBREAK AVAPERL This study
      Progressive disease 61,0 54,7 40,6
      Adverse event 13,7 21,6 33,3
      Others reasons 19,8 23,5 25,8

      Conclusion
      This retrospective study suggests that in real world setting, double maintenance is frequently discontinued for adverse event (33,3% of patients). The most frequent adverse event was renal failure (half of the cases). Further analyses are ongoing in order to identify any predictive factors for renal failure occurrence and will be presented at meeting. These results suggest that particular caution should be taken in order to preserve renal function whenever double maintenance (pemetrexed + bevacizumab) is considered in a patient with stable or responding tumour after induction chemotherapy consisting in platinum, pemetrexed and bevacizumab.