Author of

• 11745

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  P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11793

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    P2.11-048 - Nutritional status, body surface and sarcopenia are associated to dose reduction and severe gastrointestinal toxicity related to afatinib in patients with advanced NSCLC (ID 3482)

    09:30 - 09:30  |  Author(s): E.O. Macedo
    • Abstract

    Background
    Afatinib, an irreversible tyrosine kinase inhibitor of ErbB-family, has shown clinical benefits and prolonged progression free survival in EGFR mutated patients. Adverse effects related to afatinib such as diarrhea, stomatitis and rash can negatively impact on QoL and survival by interrupting treatment. Dose of TKI´s of EGFR are fixed regardless of weight or body surface (BS), which could affect the severity of treatment related toxicity.

    Methods
    We prospectively studied patients with advanced Non-small cell lung cancer (NSCLC ) treated with afatinib in order to determine if malnutrition and clinical factors are associated to higher incidence of severe toxicity. This study was approved by Ethics and Investigation Committees Prior treatment with afatinib (40mg), 84 patients was assessed. Nutritional status was assessed by Subjective Global Assessment (SGA) and muscle volume was determined by CT scan analysis using L3 as anatomic landmark (-29 +150 HU). Toxicity was obtained during 2 cycles by CTCAE 4.0, severe toxicity is defined as grades 3 and 4.

    Results
    Mean age was 59.3±14.8 years, 70.2% were women, 94% had adenocarcinoma, 91.7% had a good performance status (ECOG 0-1). Median weight and BS were 59.8±13.4 kg and 1.6±0.21 m[2]). Afatinib was indicated as 2[nd], 3[rd] and 4[th] line of treatment in 54.8%, 38.1%, and 7.12% of patients, respectively. Sixty percent of patients had some grade of malnutrition (SGA B+C). Severe diarrhea, mucositis and overall GI toxicity were present in 38.9%, 28.8% and 57.5% respectively. Fifty percent of patients required dose reduction, only 6 patients presented severe diarrhea and mucositis simultaneously with no statistical association (p=0.929). Factors associated to severe diarrhea, mucositis, overall gastrointestinal toxicity and dose reduction are shown in Table 1. Table 1 Related factors to Afatinib toxicity.

    	Diarrhea G3/4 (%)	Mucositis G3/4 (%)	All GI toxicity G3/4 (%)	Dose reduction %
    Female Male p	44.4 22.2 p=0.094	33.3 15.8 p=0.146	64.8 36.8 p=0.034	59.3 36.8 p=0.092
    ECOG 0-1 >1 P	36.9 57.1 p=0.419	24.2 71.4 p=0.018	53.1 100 p=0.017	53.0 57.1 p=0.836
    BMI ≤18.5 >18.5 P	47.1 31.6 p=0.179	38.5 17.6 p=0.05	55.9 59 p=0.79	50 56.4 p=0.584
    Body surface ≤1.7m[2 ] >1.7m[2 ] p	40.7 33.3 p=0.572	0 38.9 p=0.001	36.8 64.8 p=0.0034	36.8 59.3 p=0.092
    Malnutrition SGA A SGA B+C p	36.3 29 p=0.136	16.1 38.1 p=0.04	38.7 71.4 p=0.005	32.3 69 p=0.002
    Hemoglobin(mg/dl) <12mg/dl >12mg/dl p	68.8 30.4 p=0.005	28.1 31.2 p=0.804	50.9 81.2 p=0.03	47.4 75 p=0.05

    GI: Gastrointestinal. SGA : Subjective Global Assessment. ECOG: Eastern Cooperative Oncology Group Performance Scale.

    Conclusion
    The performance status, malnutrition and body surface are independent factors related to severe gastrointestinal toxicity to Afatinib. The only independent factor associated with dose reduction was malnutrition. This study suggests that for the initial dose selection of TKI´s of the EGFR these factors should be considered in order to reduce the risk of severe toxicity.

• 12592

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  P3.10 - Poster Session 3 - Chemotherapy (ID 210)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12647

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    P3.10-055 - Long progressive free survival to paclitaxel and cisplatin in first line is associated with better response and progression free survival to docetaxel in second line in advanced non-small cell lung cancer (ID 3458)

    09:30 - 09:30  |  Author(s): E.O. Macedo
    • Abstract

    Background
    Lung cancer is the leading cause of cancer death worldwide. Approximately 85% are of the non–small-cell lung cancers (NSCLC) histology and the majority have locally advanced or metastatic stage IV disease at diagnosis (85%). Cisplatin-based combination chemotherapy (CT) is the standard treatment in first line. Cisplatin plus paclitaxel (PT) it´s one of the most used combinations. Docetaxel (D) is approved for FDA in second line in NSCLC based in 3 phase III trials. Patients with breast cancer treated with paclitaxel (T) can respond to D. However, there is little information on lung cancer. We evaluate factors associated with response to D in patients previously treated with PT.

    Methods
    We analized consecutive patients treated in the thoracic tumors clinic of the Instituto Nacional de Cancerologia in Mexico between January 2007-december 2012 with NSCLC IV stage that previously were treated with PT and that at progression received D as second line (75mg/m2 each 3 weeks). We define as period free of Paclitaxel (PFT) the interval between the last cycle of PT and the progression of the disease, progression free survival (PFS) as interval since first cycle of CT and progression disease, and overall survival (OS) as the period from the diagnosis and death from any cause. The rate response (RR) was evaluated with RECIST criteria.

    Results
    Fifty-five patients were eligible for entry onto the study. Median age was 57.6 years (±15.1), female 54.5%, ECOG 0-1 (89.1%), cigarettes-smoking 45.5%, never smokers 54.5%; adenocarcinoma histology 74.5% and epidermoid 25.5%. The PFS to first-line was 6.7 months (IC 95% 5.8-7.6) and PFS to D was 4.3 months (IC 95% 2.8-5.9 months). The median period between last cycle of CT and progression disease was 2.99 months (IC 95% 2.1-3.9 months). The RR to D was 21.8% in all population. In patients with PFT >3 months compared with PFS <3months, the RR and PFS were 29% vs 14.3% (p 0.186) and 2.7 vs 6.7 months (p 0.021), respectively. We not found differences for type of response to first line CT neither histology subtype. The patients with partial response to D had were PFS prolonged in relation to patients with stable disease (5.3 versus 2.6 months, p 0.069).

    Conclusion
    Prior used of T not excluded for used D. Our results demonstrate that the PFT is the best predictive factor for response to D. Patients with PFT >3 months and response to D have better prognostic in relation with PFT <3months and with stable disease to D. This results must be validated in others prospective studies and Phase III trials that compared docetaxel with others therapies.