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): D.L. Macias
    • 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.