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Barbara Melosky
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MA 02 - Emerging Targets (ID 656)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:Ravi Salgia, Shun Lu
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 511 + 512
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MA 02.08 - Discussant - MA 02.05, MA 02.06, MA 02.07 (ID 10780)
11:45 - 12:00 | Presenting Author(s): Barbara Melosky
- Abstract
- Presentation
Abstract not provided
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-032 - A Randomized Phase Ii Trial of Selumetinib + Platinum-pemetrexed (Pem-c) in Kras Wildtype (Wt)/Unknown NSCLC: CCTG Ind219 (ID 9083)
09:00 - 09:00 | Presenting Author(s): Barbara Melosky
- Abstract
Background:
Selumetinib (SEL), an oral inhibitor of MEK 1 and 2, could be particularly effective in tumours with an activated Ras/Raf/MEK/ERK pathway, but has not been fully studied in KRAS WT nor in the first-line setting. The scheduling of SEL with chemotherapy might impact efficacy and/or toxicity.
Method:
IND219 is an open-label three-arm study of PEM-C±SEL. Arm A: PEM-C+SEL days 2-19; Arm B: PEM-C+SEL days 1-21; Arm C: PEM-C alone. Primary objective was response rate (ORR); secondary objectives were tolerability and progression-free survival (PFS). Pts were stratified by KRAS WT versus unknown and cisplatin versus carboplatin. Before the planned interim analysis (60 pts), pts were allocated 1:1:1 to arm A, B or C, with a plan to continue either Arm A or B plus Arm C a 3:1 ratio to ensure that the final analysis includes Arm A or B and Arm C in a 2:1 ratio. The trial would stop if neither Arm A or B had > 4 responses; if both did, the arm would be selected based on response and toxicity data. Correlative studies included genomic testing.
Result:
Arm A/B/C enrolled 20/21/21 pts. PEM-C exposure was lower with SEL (median cycles 5 versus 6 for Arm C). Seven pts on Arm A (35%; 95% CI 15-59% median duration 3.8m), 13 on Arm B (62%; 95% CI 38-82%; median duration 6.3m), and 5 on Arm C (24%; 95% CI 8-47%; median duration 11.6m) had PR, meeting the criteria to continue. PFS was 7.5m (95% CI 4.0 to 9.0 m) for Arm A, 6.7m (95% CI 4.1 to 8.2 m) on Arm B, and 4.0m on Arm C (95% CI 1.4 to 6.8 m). HR for PFS of Arm A over Arm C was 0.76 (95% CI 0.38 to 1.51, 2-sided p=0.42); HR for PFS of Arm B over Arm C was 0.75 (95% CI 0.37 to 1.54, p=0.43). After adjusting for age, performance status, gender and KRAS, PFS comparisons remained NS. Toxicity was most commonly grade 1-2, but more frequent with SEL especially mucositis, diarrhea, anorexia, dehydration, edema and rash. A high rate of venous thromboembolism (VTE) was seen in all arms, highest in Arm A (Arm A 45 % versus 14 % [p=0.11])
Conclusion:
SEL+PEM-C is associated with higher, but less durable ORR. In this small study, PFS is numerically prolonged adding SEL to PEM-C with expected additive toxicity. Further exploration of these intriguing results is ongoing.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-015 - Differential Outcomes between First and Second Generation TKIs in Patients with Activating EGFR Mutations in NSCLC (ID 8667)
09:30 - 09:30 | Author(s): Barbara Melosky
- Abstract
Background:
Both first and second generation EGFR tyrosine kinase inhibitors (TKIs) have efficacy in NSCLC with activating EGFR mutations (EGFRM+). Previous studies showed a differential benefit of second generation TKIs based on mutational subtypes but failed to show a difference in overall survival (OS). We aimed to characterize the patterns of use and outcomes of first and second generation TKIs and describe any differences with mutation subtype in the real world setting.
Method:
A retrospective review of all advanced EGFRM+ NSCLC patients treated with TKIs between the years 2010-2015 at the British Columbia Cancer Agency was performed. All time to event analyses were performed from date of diagnosis of metastatic disease. Multivariate regressions were performed to examine for associations of OS, treatment and mutation subtypes.
Result:
500 patients were eligible for analysis: 283 patients had an exon 19 deletion (del19), 185 had an exon 21 L858R mutation and 32 were not specified or have mutational variants such as G719var. Patient characteristics in the del19 vs. L858R group were similar: 69%/66% were female, 66%/71% were never smokers, 90%/89% were adenocarcinoma, 20%/20% had CNS metastases at diagnosis, 85%/84% had de novo metastatic disease and 41%/37% received ≥2 lines of therapy (all p>0.05). The del19 cohort had less Asians (46% vs 58%, p=0.02) and were younger (median age 63 vs. 69, p=0.02) compared to L858R group. In the del19/L858R cohorts, 81%/19% and 84%/16% received a first and second generation TKI respectively. 43% of patients receiving a second generation TKI required a dose reduction to manage the toxicity and one patient discontinued the medication. OS in the entire cohort was 26 months, with the del19 group surviving longer compared to the L858R cohort (27 vs. 22 months, p<0.01). In multivariate analysis, factors associated with improved OS were del19 (HR0.7, p<0.01 95%CI0.6-0.9), treatment with a second generation TKI (HR0.6, p=0.01 95%CI0.5-0.9) and absence of CNS metastases (HR0.7, p<0.01 95%CI0.5-0.9). First line treatment with a second generation TKI was associated with better OS compared to a first generation TKI (HR0.6, p=0.04 95%CI0.3-1.0). This was statistically significant only in the del19 subgroup (HR0.4, p=0.04 95%CI0.2-1.0).
Conclusion:
Use of a second generation TKI in EGFRM+ advanced NSCLC is associated with improved OS in multivariate analyses controlling for other prognostic factors. This was significant in the entire group and in the del19 cohort, supporting the use of mutational subtype to guide therapy decisions.
