Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

M. Lazaro



Author of

  • +

    P1.13 - Poster Session 1 - SCLC (ID 200)

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

      P1.13-005 - Paclitaxel and Irinotecan in Platinum Refractory or Resistant Small Cell Lung Cancer: a Galician Lung Cancer Group experience. (ID 2340)

      09:30 - 09:30  |  Author(s): M. Lazaro

      • Abstract

      Background
      Patients with Small Cell Lung Cancer (SCLC) whose disease progresses during or shortly after treatment with platinum, have a poor prognosis. Paclitaxel (P) and irinotecan(I) have demonstrated activity both as monotherapy as in combination regimen for this neoplasm. We present preliminary data from our experience in patients with SCLC refractory or resistant to platinum.

      Methods
      We included patients with measurable disease that had progressed during or within six months of first-line chemotherapy based on platinum, with an Eastern Cooperative Oncology Group (ECOG) performance status <2, adequate liver, renal and bone marrow function. They were treated with (P): 75 mg/m2 and (I): 50 mg/m2, both drugs administered on days 1 and 8 of a 21 day cycle. Treatment was maintained until disease progression and/or unacceptable toxicity.

      Results
      We included 24 patients with a mean age of 59.5 years (43-79) and with metastases in two or more locations in 21 of them (87.5%). A median of 4 cycles of treatment was administered and eight patients (33.3%) received six or more cycles. The main reason for discontinuation of chemotherapy was disease progression, observed in 20 patients (83.3%). Partial response was documented in 16 patients (66.6%), stable disease in three (12.5%) and disease progression in five (20.8%). The median survival time was 24,9 weeks and the 1-year survival time was 22%. There have been no treatment-related deaths. The clinical and hematologic toxicities most frequently observed were grade 1 and 2: nausea (n:7; 29,2%), asthenia (n:7; 29,2%), anorexia (n:6; 25%), diarrhea (n:4; 16,6%), anemia (n:16; 66,6%) and neutropenia (n:12; 50%). There was one (4,1%) grade 4 and two (8,3%) grade 3 neutropenia. There were no cases of grade 4 clinical toxicity and there were eight (33,3%) grade 3 : three of diarrhea (12,5%), two hepatic (8,3%) and three of asthenia (12,5%).

      Conclusion
      This (P) and (I) regimen is an effective and well tolerated option for this subgroup of poor prognosis patients with SCLC. We still continue including patients in this protocol, which ensures future communications of the same.

  • +

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

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

      P3.09-016 - A phase II study of cisplatin and oral vinorelbine concomitantly with radiotherapy in locally advanced non-small-cell lung cancer treatment: Eficacy and safety results. (ID 2687)

      09:30 - 09:30  |  Author(s): M. Lazaro

      • Abstract

      Background
      It has been shown an improvement in survival with concurrent chemoradiation versus the sequential administration of both treatment modalities. In patients with unresectable stage III disease, chemotherapy may best be started soon after the diagnosis of unresectable NSCLC has been made. Cisplatin (CDDP) plus oral vinorelbine (OV) as induction and concomitant regimen with radiotherapy (RT) has shown good efficacy outcomes and safety profile (Vokes, Fournel, Krzakowski). The objective of this study was to evaluate the effectiveness and toxicities of the combination of CDDP and OV given at full doses concomitantly with RT in locally advanced (LA) non-small-cell lung cancer (NSCLC).

      Methods
      Between February 2010 and December 2011, 48 chemo-naïve patients (p) with histologically confirmed unresectable stage IIIA/IIIB LA NSCLC were treated. Treatment consisted of 4 cycles (cy) of OV 60 mg/m[2] on days 1 and 8 and CDDP 80 mg/m[2] every 3 weeks plus RT 66 Gy starting on day 1, cy 2. The primary objective is the overall response rate (ORR) using RECIST 1.0. A standard Fleming two stage design was used. The sample size calculated with a type 1 error of 0.05 and type 2 error of 0.01, taking P~0~ 20% and P~1~ 40%. The study was approved by the local Ethical Committees of the participating institutions.

      Results
      Patient’s characteristics were: Median age 61 years (range 34-72); ≥ 65y 42%; males 89.6%; PS0 42% / PS1 58%; smokers 52%; adenocarcinoma 30% / squamous 64%; stage IIIA 46% / IIIB 54%. Median of days between initial diagnosis and study start was 28 days. 75% p completed the treatment as per protocol. Relative dose intensities of OV and CDDP were 97%/98%, respectively. 14.7% of cy were delayed, 11.8% due to toxicity. Dose of day 8 OV was canceled or delayed in 8.2% of cy. Hematological toxicities (% p): grade (g) 3/4 neutropenia 33.3%; g3 anemia 12.5%; g3/4 thrombocytopenia 16.6%; febrile neutropenia concomitant during CT-RT 14.6%. Non-hematological toxicities (% p): g3 esophagitis 12.5%; g3 dyspnea 4.2%, g3 vomiting 4.2%, g3-4 infection 4.2%. 2 treatment-related deaths were reported, both during cycle 1. 42 p (87.5%) received RT, 7.1% under 60 Gy, 23.8% with RT delays or interruptions due to adverse events. 44 p were evaluable for response. ORR 77.3% [CI 95%, 62.2-88.5], DCR 88.6% [CR 2 p (4.5%), PR 32 p (72.7%), SD 5 p (11.4%)]. Median follow-up was 19 months (m) (range 0.47-39.4). Median progression free survival (PFS), 12 m [CI 95%, 7.3-16.6]; 1-year PFS, 48.3% [CI 95%, 33.6-63], 2-year PFS, 30% [CI 95%, 15.8-44.2]. Median time to progression (TTP), 13.3 m [CI 95%, 9.7-16.9]; 1-year TTP, 51.7% [CI 95%, 36.9-66.6], 2-year TTP, 33.3% [18.5-48.1]. Median overall survival was not reached; 1-year and 2-year survival rates were, 72.3% [CI 95%, 59.6-85.1] and 49.4% [CI 95%, 33.8-64.9], respectively.

      Conclusion
      This prospective phase II trial shows that the schedule of cisplatin plus oral vinorelbine concomitant with radiotherapy from 2[nd] cycle obtains a good efficacy with an acceptable safety profile. Clinical trial information: EudraCT Number: 2009-010436-17

  • +

    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
    • +

      P3.11-017 - Observational post-authorization prospective study to characterize the incidence of EGFR positive mutation (M+) in advanced or metastatic non-small cell lung cancer (aNSCLC) patients (P) and their clinical management in Galicia (NCT01717105): A Galician Lung Cancer Group study (GGCP 048-10) (ID 1695)

      09:30 - 09:30  |  Author(s): M. Lazaro

      • Abstract

      Background
      The presence of mutations in the gene encoding the Epidermal Growth Factor Receptor (EGFR) predicts that P with aNSCLC may respond better to Tyrosine Kinase Inhibitors (TKIs). Recently, the Spanish REASON study has reported that the rate of EGFR mutations is 11.6% in Spain; however the mutation rate and the clinical management of aNSCLC carrying EGFR mutations in Galicia are still unknown.

      Methods
      All newly diagnosed aNSCLC P in 9 Galician centers were prospectively included for a 13-month period. P with M+ disease were followed for at least 9 months (m) in order to characterize their clinical management. Mutation testing was performed on available tumor and plasma samples, through a central laboratory using the EGFR RGQ PCR Kit™ (Qiagen). Pre-planned exploratory objectives included comparison of EGFR mutation status between matched baseline tumor and plasma samples.

      Results
      From February 2011 to March 2012, 198P were included in the study. Median age was 65.5 years (range 34-85). 76.3%P were men, 21.7% were never-smokers, 45.5% ex-smokers, and 32.8% current smokers. PS 0-1: 67.1%. 78.3% had non-squamous histology (68.7% adenocarcinoma, 8.1% large-cell carcinoma, 1% adenosquamous carcinoma, and 0.5% non-specified) and 21.7% p had squamous-cell carcinoma. Sample type provided included: 57.6% tissue, 42.4% cytology. Median turnaround time (TAT) was 8 days. Mutation rate in evaluable samples: 13.6% in tumor, tissue or cytology (25P) (11P had exon 19 deletion, 8P L858R mutation, 2P exon 20 insertions and 1P L861Q mutation); 5.9% in plasma. Tumor and plasma EGFR mutation status concordance rate was 90.8%.Plasma test sensitivity was 40%. Mutation rate did not vary by sample type (13.9% tissue, 13.2% cytology). A higher mutation rate was found in never smokers (42.5%), females (38.6%) and adenocarcinoma (19.8%). 23 out of 25 M+ P received first line treatment and 2P only best supportive care. 21P were treated with TKI (Gefitinib), 1P with chemotherapy (CT) (Cisplatin/docetaxel/bevacizumab) and 1P with CT+TKI (Carboplatin+Gefitinib). 20P were evaluated for response. 3P were lost for follow up. At data cut off (31/12/2012), with a median follow up of 9.8m, 14P had partial response (70%), 2 stable disease (10%) and 4P progressive disease (20%). Median progression free survival was 9.7m. 8 out of 20P (40%) received 2[nd] line treatment (7 CT and 1 TKI). 12 out of 25P had died, 3P were lost for follow up and 10P were still alive.

      Conclusion
      Mutation analysis is feasible in clinical practice for aNSCLC patients in Galicia and allows the customization of treatment based on molecular criteria. Despite of the relatively small number of patients in this study, EGFR testing in plasma has a low sensitivity and therefore should not substitute tissue testing although it could be an alternative for those patients without tissue samples.

    • +

      P3.11-019 - Gefitinib efficacy in EGFR mutated Non Small Cell Lung Cancer (NSCLC) patients based on type of mutation: a study from the Galician Lung Cancer Group. (ID 1710)

      09:30 - 09:30  |  Author(s): M. Lazaro

      • Abstract

      Background
      Screening for Epidermal Growth Factor Receptor (EGFR) mutation is a key molecular test for management of lung cancer. Patients who respond well to an EGFR inhibitor harbor certain mutations in the EGFR exons 18, 19 or 21. An additional mutation in EGFR exon 20 is known to be responsible for acquired resistance to this therapy.

      Methods
      We conducted an analysis of Galician advanced lung cancer patients who were tested positive for EGFR kinase domain mutations determination and were treated with gefitinib. Frequency and type of EGFR mutations and the clinical response in our area were explored. The aim is to analyse the pattern of response, toxicity, progression free survival and overall survival based on the type of EGFR mutation.

      Results
      Forty-six patients with EGFR mutations were collected, 36 women and 10 men. The median age was 67 years (43-86). Majority of the patients in the study had PS 0-1 (93%) and adenocarcinoma (96%) in the pathological study. The most frequent sites of metastasis were lymph nodes (59%), bones (33%), lung (33%) and pleura (33%). The median duration of treatment was 6 months. Progression disease was the most frequent reason of discontinuation of gefitinib; in 9 patients was discontinued because of toxicity. Ten patients were switched to cytotoxic chemotherapy and 10 patients continued with erlotinib. Twenty patients were detected to be positive for mutation in exon 19, 4 patients in exon 20 and 20 patients in exon 21. The L858R point mutation in exon 21 was observed in 14 patients and the L833F point mutation in the same exon was observed in 1 patient. Thirty-five patients were included in the response analysis. The response ratio to gefitinib was 57%. Depending on the type of mutation, the response in exon 19 mutation patients was 64%, in exon 20 patients was 0% and in exon 21 patients was 60%. Rash or acne was the most frequent toxicity (48%), only 2% was grade 3-4. Diarrhea and dysnea were the main toxicities grade 3-4 (9% both), without statistical differences based on type of mutation (p=0.78) . Progression free survival (PFS) of patients with EGFR mutations was 6 months. Patients with mutation in exon 19 had 9 months compared to 6.4 months for patients with exon 21 mutation, presenting a statistically significance difference (p=0.002). Overall survival (OS) was 17 months for EGFR mutations patients (19 months for exon 19 mutation patients and 14 months for exon 21 mutation patients; p=0.119)

      Conclusion
      Pacients in our area with exon 19 EGFR kinase domain mutations treated with gefitinib have higher PFS compare to exon 21 EGFR kinase domain mutations. Exon 20 mutation in our patients is responsible for resistance to gefitinib.