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Grainne Mary O'Kane



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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-42 - Real-World Evaluation of Tolerability in Older Adult Patients (≥75 Years Old) with EGFR-mutated NSCLC (ID 13289)

      16:45 - 18:00  |  Author(s): Grainne Mary O'Kane

      • Abstract
      • Slides

      Background

      NSCLC patients carrying EGFR mutations are diagnosed across a wide age distribution. Although EGFR tyrosine kinase inhibitors (TKIs) are generally well tolerated, there remains a paucity of real-world data on toxicity and health utility scores (HUS) in older patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A longitudinal observational study evaluated health-related quality of life (HRQoL) using HUS through the EQ-5D questionnaire, and common EGFR-TKI toxicities using PRO-CTCAE in NSCLC outpatients carrying EGFR mutations. Patients were classified into two groups: older (>75 years) and younger (<75 years). Patient characteristics and outcomes were extracted from chart review; patients were classified as having stable or progressive disease according to imaging findings. HUS and PRO-CTCAE results were compared descriptively.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 240 patients and 774 encounters, 52 patients (22%; comprising 157 encounters) were aged ≥ 75 years. Gender and race were similarly distributed in both age groups: 63% of older patients and 70% of younger (<75 years) were female; 56% of older patients and 53% of younger patients were Asian. Use of gefitinib in older patients was much higher than other drugs: among 147 patients who received gefitinib, 27% (40 patients) were older, compared to 15% (5/33) for osimertinib and 15% (3/20) for erlotinib. Of patients receiving afatinib (n=11) and chemotherapy (n=32), none were ≥ 75 years. The following table describes HUS and PRO-CTCAE results by treatment and age group for stable patients.

      Older Adults (75 years)

      Younger Adults (<75 years)

      N

      HUS, mean (SD)

      PRO-CTCAE*, median [IQR]

      N

      HUS, mean (SD)

      PRO-CTCAE*, median [IQR]

      Stable on gefitinib

      34

      0.83 (0.20)

      4.5 [0,16]

      77

      0.80 (0.15)

      4 [0,15]

      Stable on osimertinib

      5

      0.80 (0.23)

      13.5 [0,17]

      22

      0.87 (0.12)

      0 [0,13.5]

      Stable on erlotinib

      3

      0.82 (0.08)

      0 [0,9]

      11

      0.80 (0.14)

      0 [0,16]

      *Higher PRO-CTCAE indicates more severe toxicities/symptoms.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In a real-world evaluation, patients 75 years or older comprised almost a quarter of all patients with EGFR-mutant advanced NSCLC. Afatinib and chemotherapy were not used at all in this population. Gefitinib was used most commonly, with similar toxicities and health utilities between older and younger patients. Osimertinib and erlotinib were used too infrequently in this study for conclusive age comparisons.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.13-11 - PRO-CTCAE Toxicities in Advanced NSCLC Patients with EGFR Mutations: A Real World Assessment (ID 12998)

      16:45 - 18:00  |  Author(s): Grainne Mary O'Kane

      • Abstract
      • Slides

      Background

      The Patient Reported Outcomes of the CTCAE (PRO-CTCAE) tool has not been evaluated in a real-world study of EGFR-mutation positive patients treated with TKIs/chemotherapies. We evaluated its role in capturing clinically-significant toxicities.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A longitudinal observational study evaluated common EGFR-TKI toxicities using PRO-CTCAE, measured on a five-point scale (1=no symptoms to 5=very severe symptoms) in outpatients with EGFR-mutated (EGFRm) advanced NSCLC.

      4c3880bb027f159e801041b1021e88e8 Result

      Toxicity information was collected for 709 follow-up visits (encounters) from 232 patients. Median age was 64 (range:29-96), 161 (69%) were female and 124 (53%) were Asian. 85 (37%) already had brain metastases at first encounter. 485 encounters were observed from patients stable on treatment, and 187 from patients progressing or with documented progression on their current treatment. 24 patients were treated with osimertinib (97 encounters, 97% in second/subsequent-line), 136 with gefitinib (324 encounters, 95% in first line therapy), 42 were receiving other EGFR-TKIs (118 encounters, 53% in second/subsequent-line), and 29 with chemotherapy (73 encounters, 96% second/subsequent-line). The table below summarizes the treatment-related PRO-CTCAE toxicities self-graded as moderate-to-very-severe by EGFRm patients.

      Proportion of patients reporting highest grade of toxicity as grade 3-5, by PRO-CTCAE

      Gefitinib

      Osimertinib

      Other EGFR TKI

      Chemotherapy

      Diarrhea

      17%

      18%

      24%

      8%

      Constipation

      12%

      4%

      12%

      16%

      Decreased appetite

      10%

      7%

      14%

      26%

      Nausea

      6%

      3%

      4%

      24%

      Vomiting

      1%

      2%

      3%

      16%

      Fatigue

      18%

      12%

      23%

      42%

      Numbness and Tingling

      6%

      7%

      10%

      16%

      Skin Rash

      23%

      12%

      20%

      9%

      Visual Disorders

      (includes dry eye)

      4%

      0%

      3%

      4%

      Total PRO-CTCAE Score, MEDIAN [IQR]

      4 [0,16]

      0 [0,15]

      6 [0,17]

      10 [0,21]

      8eea62084ca7e541d918e823422bd82e Conclusion

      Osimertinib therapy had the most favorable self-reported toxicity profiles of all the therapies in EGFRm patients, followed by gefitinib. Chemotherapy generated the greatest toxicities. The use of PRO-CTCAE was well-accepted by patients in a clinical setting. This confirms trial data supporting favorable toxicities with osimertinib compared to other therapies for EGFRm NSCLC patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.13-15 - Detection of EGFR Mutations in cfDNA and Development of Resistance (ID 12634)

      16:45 - 18:00  |  Presenting Author(s): Grainne Mary O'Kane

      • Abstract

      Background

      Peripheral blood sampling for T790M in patients (pts) failing initial EGFR-TKIs is now standard practice. The value of longitudinal sampling in pts is unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A study of cell free (cf) DNA analysis in pts with EGFR mutated(m) non-small cell lung cancer (NSCLC) is ongoing at the Princess Margaret Cancer Centre. The ThermoFisher OncomineTM lung assay detecting single nucleotide variants and indels to a limit of 0.05-0.1% variant allele frequency (VAF) was used. Patient clinical details and outcomes were collected prospectively.

      4c3880bb027f159e801041b1021e88e8 Result

      From Oct 2016-Feb 2017, 73 pts with EGFRm NSCLC enrolled and first blood samples were analysed. Most (92%) had mutations in del19 or L858R, including 1 pt with del19/S768I. Uncommon EGFRm were present in 6 (G718X, L861Q, exon20ins). Detectable levels of cfDNA were found in 50 pts (68%). Of 64 pts either starting an EGFR-TKI (n=11,17%), receiving a TKI without progression (PD) (23, 36%) or with PD on a TKI (30, 47%), the presence of the primary EGFRm (n=39, 61%) strongly associated with pre- 1st TKI or PD, p=0.03. Of 53 pts receiving a TKI, the presence of T790M in 31 (58%) associated with PD (p=0.04). Where pts had no radiologic PD evident, the median progression free survival (PFS), taken from blood draw, was 2.1 months (mths) versus 10 mths (HR 2.22, 95% CI: 0.89-5.54 p=0.08) when the primary EGFRm was detected. If T790M was present in cfDNA, the median PFS was 3.0 months versus 9.7 mths, (HR 4.59, 95% CI: 1.43-14.73 p=0.005). In univariable regression analyses the %VAF of the primary EGFRm correlated with PFS (HR 1.15, 95%CI: 1.02-1.29, p=0.02) with a trend in the %VAF of T790M (HR 1.16 95% CI:0.99-1.37, p=0.08). T790M was detected in 3 of 4 pts with T790M -ve tissue, and other co-occurring EGFRm were found in 10 pts including K745R in a pt receiving first-line osimertinib. TP53 (n=10), KRAS (1), PI3KCA(1) and ALK(2)gene mutations were also detected. Interestingly, in 1 pt receiving chemotherapy with T790M+ disease, both the primary EGFRm and T790M were detected in blood at the time of PD.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In addition to the emergence of resistance mutations, the presence of the primary EGFRm in pts receiving EGFR-TKIs may associate with a shorter PFS and therefore may be useful in longitudinal analyses of cfDNA to direct therapy.

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