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Tarje O Halvorsen
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-09 - Randomized Trial Comparing Maintenance Pemetrexed with Observation Followed by Pemetrexed at Progression in Advanced NSCLC (Now Available) (ID 1304)
09:45 - 18:00 | Author(s): Tarje O Halvorsen
- Abstract
Background
Previous placebo-controlled studies show that maintenance treatment with pemetrexed prolongs progression free survival (PFS) and overall survival (OS) in advanced non-squamous non-small-cell lung cancer (NSCLC) patients who do not progress on induction platinum-doublet chemotherapy. There were, however, a few limitations of these studies: Few on the control arms received pemetrexed at progression, few patients >70 years were enrolled, and patients with performance status 2 (PS2) were ineligible.
Method
In this open phase III trial, patients with stage IIIB/IV non-squamous NSCLC ineligible for curative treatment who had PS 0-2, and non-progression after four courses of carboplatin (AUC=5) day 1 + vinorelbine (25 mg/m2 IV day 1 and 25 mg/m2 IV or 60 mg/m2 PO day 8) were randomized to receive immediate pemetrexed maintenance therapy or observation followed by pemetrexed at progression. There was no upper age limit. The primary endpoint was OS, secondary endpoints were PFS and toxicity. To demonstrate an improvement in median OS from 6 to 8 months (from the time of randomization) with an α=0.05 and β=0.20, 198 patients were required on each arm. Accounting for a drop-out of maximum 10%, we aimed to randomize 436 patients.
Result
105 patients were randomized between May 2014 and September 2017 at 19 hospitals in Norway (maintenance: n= 54, observation: n=51). Inclusion was stopped prematurely due to poor recruitment after immunotherapy became available. Median age was 67 years (range 46-83), 34% were >70 years, 14% had PS 2, 93% stage IV, and 54% were women. 75% of the patients received pemetrexed at progression. The median number of pemetrexed courses were 4 (maintenance: 3, observation: 4; p=0.265). Patients in the maintenance-arm had a significantly longer PFS (median 3.1 vs. 1.9 months; p=0.02), and a 2 months longer median OS (12.0 vs. 10.0 months; p=0.10). In a Cox regression analysis adjusting for baseline patient and disease characteristics (gender, stage of disease, PS), there was a trend towards a statistically significant difference in OS (HR 0.67 95% CI 0.436-1.030; p=0.068). There were no significant differences in toxicity between those who received maintenance therapy and those who received pemetrexed at progression.
Conclusion
Maintenance pemetrexed therapy prolongs PFS and with a trend towards improved OS in non-squamous NSCLC compared with observation followed by pemetrexed at progression in a cohort including more elderly patients than previous studies of maintenance pemetrexed therapy and when allowing PS2 patients.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-03 - Prognostic Value of Mutated KRAS in Circulating Tumor DNA Prior to Therapy in Patients with Lung Adenocarcinoma (ID 1901)
10:15 - 18:15 | Author(s): Tarje O Halvorsen
- Abstract
Background
Studies show an association between total tumor load and the amount of circulating cell-free tumor DNA (ctDNA) in blood, and that detectable ctDNA is a negative prognostic factor. KRAS mutations (mutKRAS) are the most common oncogenic drivers in lung adenocarcinomas (lungAC) and are found in 25-30 % of the patients. We hypothesized that the concentration of mutKRAS in plasma ctDNA is associated with outcomes in patients with lungAC harboring KRAS mutations, and aimed to investigate whether there was an association with disease stage, progression free (PFS) and overall survival (OS).
Method
Blood samples collected prior to first treatment from 61 lungAC-patients with known mutKRAS in tumor DNA were analyzed. Digital droplet PCR was used for detection and quantification of mutKRAS in the plasma samples. The false positive rate for each mutKRAS assay was determined using cfDNA from healthy donors. A sample was defined as "positive" if the mutKRAS level was above the false positive rate. Mann-Whitney U test was used to compare PFS and OS between those with not-detectable and those with detectable mutKRAS ctDNA. Log-rank and Cox proportional hazard methods were used for survival analyses. One-way ANOVA was used to compare the concentration of mutKRAS between disease stages.
Result
Median age was 68 years (range 47-83), all patients were former/current smokers, 39.3% were men; 39.3% had stage I, 18.0% stage II, 24.6% stage III and 18.0% stage IV; 55.7% had performance status (PS) 0, 39.3% PS 1, and 4.9% PS 2; 70.5% underwent surgery, 4.9% curative radiochemotherapy and 24.6% palliative treatment. Overall, 26.2% had detectable mutKRAS in ctDNA with a median of 119.68 (range:16.66-1208) copies/ml plasma.The proportion of patients with mutKRAS in plasma ctDNA increased with higher disease stage (stage I: 0%, II: 18%, III: 47%, and IV: 64 %; p=0.006). Patients with plasma mutKRAS had significantly shorter PFS ( 11.9 vs. 23.5 months; p=0.012) and OS ( 15.8 vs. 23.5 months; p=.0.010) than those without. The mutKRAS ctDNA concentration was significantly associated with both shorter PFS (HR 1.009, 95% CI 1.004-1.013; p<0.001) and OS (HR 1.007, 95% CI 1.003-1.011; p=0.001).The associations remained statistically significant in the multivariate analyses adjusting for baseline characteristics (gender, age, disease-stage, PS, treatment) for both PFS (HR 1.009, 95% CI 1.003-1.014; p=0.002) and OS (HR 1.008, 95% CI 1.002-1.015; p=0.008).
Conclusion
The concentration of plasma mutKRAS increased with higher disease stage. Patients with detectable plasma mutKRAS had worse PFS and OS than patients without. The concentration of mutated KRAS was independently associated with worse PFS and OS.
