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W. Ong



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    O03 - NSCLC - Targeted Therapies I (ID 113)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O03.03 - Outcomes of NSCLC patients on Phase I Trials: The Importance of Molecular and Patient Selection (ID 3349)

      10:50 - 11:00  |  Author(s): W. Ong

      • Abstract
      • Presentation
      • Slides

      Background
      With recent successes of targeted therapeutics, there has been increased enthusiasm to enroll patients with NSCLC into phase I trials. Most phase I prognostic indices have been derived from patient populations where NSCLC is underrepresented.

      Methods
      Retrospective review of NSCLC patients enrolled between 2005-2012 at National Cancer Centre Singapore was performed, collating data on demographics, molecular profiles, trial characteristics and clinical outcomes (using RECIST criteria) to identify prognostic factors to improve patient selection.

      Results
      167 patients were treated on 20 phase I trials. Median (range) age 60.7 years (22.7–84.7), 58% male, adenocarcinoma/squamous/NOS/others (75.4%/9.6%/12.6%/2.4%). 13% were at high risk of nutritional deficiency (BMI<18.5), and ECOG 0(21%)/1(77%)/2(2.4%). Median (range) prior chemotherapy was 2 (0-6) and 99% received at least one treatment line. Class of agents include anti-angiogenics (50.3%), signal transduction pathway inhibitors (STPi) 46%. Only 4.2% received cytotoxics alone. 86.2% were on combination regimens, of which two-thirds on combinations of chemotherapy and small molecule. Between 2008-2012, proportion of patient tumors with molecular alterations identified increased from 5.5% to 62.5%, facilitating enrolment into trials designed for a specific genotype (or “matched” trials). 35% and 7.8% of patients participated on trials targeting EGFR and ALK alterations respectively. With a median follow up of 8.7 months, progression free survival was 3.9m (95%CI:3.4–5.8), overall survival (OS) 10.4m (95%CI:8.0–11.7). Among evaluable patients, 24.8% (95%CI:18.2–32.5) had complete/partial response; clinical benefit rate (CBR) 75.8% (95%CI:68.2–82.4). 90-day mortality (90DM) was 15%. Patients participating in “matched” trials had a lower risk of death (HR 0.55 [95%CI:0.38-0.78] p<0.001) compared to those on unselected or “unmatched” trials (median OS 11.9 v 7.6). On univariate analysis, low BMI<18.5, ECOG>0, ≥3 metastatic sites, presence of bone metastasis, low albumin (<35), low Hb (<12), ≥ 3 prior lines of chemotherapy and non-participation in a "matched" trial were significant negative prognostic factors for OS. On multivariate analysis, ECOG, number of metastatic sites, albumin and trial type (targeting EGFR/ALK/others), emerged as independent variables. These factors were used to construct a prognostic nomogram to predict OS at 3, 6 and 12m. Of 12 published prognostic indices, 8 models were validated in our patient cohort, with the highest c-index being 0.66. Pairwise comparison against these 8 (7 tumor agnostic; 1 NSCLC) prognostic indices, found the nomogram to be superior in predicting OS, with a c-index of 0.74.

      Conclusion
      This is the largest analysis of phase I NSCLC patients using individual patient data. Outcome of NSCLC patients in phase I trials is promising with CBR 76% and median OS 10.8m. Our nomogram – comprising of ECOG, albumin, number of metastatic sites, participation in a “matched” trial – is uniquely derived from NSCLC patients and was a better predictor of OS compared to 8 published phase I prognostic scores.

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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-040 - Lung cancer outcomes in an era of more options - Survival analysis from an Asian cancer center (ID 2193)

      09:30 - 09:30  |  Author(s): W. Ong

      • Abstract

      Background
      Lung cancer therapy has changed in the last decade with the advent of EGFR tyrosine kinase inhibitors (TKI) and newer chemotherapeutics such as pemetrexed. Most of these benefits have been limited to lung adenocarcinoma and not other histological subtypes. In addition, this has translated to improved progression free survival benefits but no apparent overall survival benefits in some of the phase III studies conducted. We hypothesized that the benefits seen in these phase III clinical trials would translate to improved overall survival in the wider population of patients (pts) treated in a cancer center.

      Methods
      We conducted a survival analysis of all primary stage 3B/4 lung cancer diagnoses available from a cancer center database between 1 Jan 2000 and 31 Dec 2012. The diagnoses were identified based on ICD-9 162 and ICD-10 C34. Recurrent lung cancers were excluded. Histological classification for analysis was based on the IASLC system. Molecular data from adenocarcinoma (AC) was available with routine testing from 2010. Treatment given in the form of pemetrexed and EGFR TKI was also tracked from the pharmacy system from 2001. Vital status was checked against the National Registry of Births and Deaths as at 31 March 2013. The primary endpoint was overall survival (OS) which was defined from the time of diagnosis till death from any cause or last follow-up and estimated using Kaplan-Meier method. Log-rank test was used to compare survivals. Jointpoint regression models were used for trend analyses.

      Results
      A total of 5320 cases of stage 3B/4 primary lung cancer diagnoses were identified. The cases were predominantly male (65%) and Chinese (81%). The median age at diagnosis and gender distribution among the diagnoses in each year remained stable over time. Non-small cell lung cancer (NSCLC) made up 92% of all diagnoses. NSCLC subtypes were adenocarcinoma (52%), squamous (13%), large cell (2%), and Others (25%). EGFR mutation rate among 708 tested cases was 55%, and ALK translocation rate among 108 tested cases was 9%. The jointpoint regression model identified 2005 as a significant turning point in improvement in median OS. Hence comparing 2001-2005 and 2006-2010, the median OS for the entire cohort improved from 8.0 mths (95% CI, 7.1-8.7) to 9.5 mths (95% CI, 8.9–10.2), p = 0.001. This median OS survival benefit was contributed by OS benefits in AC 10.3 mths (95% CI, 9.3-11.8) vs 13.3 mths (95% CI, 12.1 -14.5). The turning point for improvement for median OS survival coincided with increased usage of EGFR TKI and pemetrexed from 2006 and 2008 respectively.

      Conclusion
      There is median OS benefit in lung cancer treatment outcomes tracked over a decade. This observed benefit is in tandem with the increased use of drugs that have clinical benefit in adenocarcinoma. Unmet needs remain for both small cell lung cancer and other NSCLC subtypes.