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O03 - NSCLC - Targeted Therapies I (ID 113)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
O03.03 - Outcomes of NSCLC patients on Phase I Trials: The Importance of Molecular and Patient Selection (ID 3349)
10:30 - 12:00 | Author(s): D.W. Tai
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.
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.
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.
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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