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L.C. Villaruz
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-007 - LCMC2: Expanded Profiling of Lung Adenocarcinomas Identifies ROS1 and RET Rearrangements and TP53 Mutations as a Negative Prognostic Factor (ID 8338)
09:30 - 09:30 | Author(s): L.C. Villaruz
- Abstract
Background:
The Lung Cancers Mutation Consortium (LCMC) is a multi-institutional effort where 16 sites identify oncogenic drivers and pool data to assess the impact of targeted therapies in patients with lung adenocarcinomas. We now report the results of the second patient cohort (LCMC2) with an expanded multiplex molecular panel to include RET and ROS1 and tumor suppressors.
Method:
904 patients with centrally confirmed stage IV lung adenocarcinomas who were candidates for therapy had at least one of 14 oncogenic drivers assessed in a CLIA-compliant laboratory using genotyping, FISH, massively parallel sequencing (NGS), and immunohistochemistry (IHC) analyses.
Result:
Among 423 patients tested for all 14 targets, we found a driver in 65%. Mutated KRAS was found in 31%, sensitizing EGFR in 14%, MET amplification in 5%, ALK rearrangements in 4%, BRAF V600E in 3%, and HER2 in 3%. Rearrangements in RET and ROS1 were each found in 2% (CI 1 to 3%). Using IHC, PTEN loss was found in 8% (CI 6 to 11%) and MET expression in 58% (CI 55 to 61%). Use of targeted therapies in patients with EGFR, HER2, or BRAF mutations, ALK, ROS1, or RET rearrangements, and MET amplification was associated with a gain in overall survival of 1.5 years relative to those with the same drivers not receiving targeted therapy and a gain of 1 year relative to those without an actionable driver. Current and former cigarette smokers derived a survival benefit from targeted therapies similar to never smokers (p=0.975). Among 154 patients who had all drivers assessed and NGS testing in addition, any TP53 mutation was associated with poorer survival among those with EGFR, ALK, or ROS1 (p=0.014). STK11 was detected in 11%, all in patients with KRAS mutations.
Conclusion:
Using an expanded testing panel, LCMC2 demonstrates the survival benefit of matching targeted treatments to oncogenic drivers in patients with lung adenocarcinomas, identifies additional prognostic factors, and supports the performance of multiplex molecular testing on specimens from all individuals with lung adenocarcinomas irrespective of clinical characteristics. We detected either MET amplifications or HER2 mutations in 7%, together more than the 4% with ALK. A targeted drug is available in the United States for 35% of patients with lung adenocarcinomas. The routine use of massively parallel sequencing (NGS) detects both targetable drivers and tumor suppressor genes that have significance for therapy selection and prognosis. Supported by Free to Breathe
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P3.03-031b - Results of a Phase II Study of Stereotactic Radiosurgery Followed by Erlotinib for Patients with EGFR Mutation and Progression in 5 or Fewer Sites (ID 10207)
09:30 - 09:30 | Author(s): L.C. Villaruz
- Abstract
Background:
For patients with metastatic EGFR mutated NSCLC, 1[st] line treatment with EGFR TKIs such as erlotinib result in a median PFS of about 10 months. In patients with a limited number of progressing lesions, local ablation therapy (LAT) of progressive lesions followed by re-initiation of TKI has shown promise in retrospective studies but to date this strategy has not been testing in prospective fashion.
Method:
As part of an IRB approved open label prospective phase II trial, patients with EGFR mutated NSCLC and immediate progression on a TKI in < 5 locations were treated with stereotactic radiosurgery (SRS) to progressing lesions followed by re-initiation of erlotinib. Our primary endpoint was PFS, and we hypothesized that it would be at least 3 months.
Result:
25/40 planned patients were enrolled; data are available on 23 and will be updated prior to the conference to include 25. By local reporting, 14 had exon 19, 5 had exon 21, 1 had compound exon 18 and exon 20, 1 had compound exon 19 and EML4/ALK and 2 were unknown. 65% were female, all were non-Hispanic white, median age 62.5, PS0 65.2%/PS1 34.8%, median Charlson Comorbidity Index 6, and 71.4% were never smokers. Median number of lesions treated was 1 (range 1-3). There were no G3-4 AEs to SRS. Two subjects had grade 3 rash on erlotinib. Median PFS post treatment was 5.8 months (95% CI, 2.5 to 11.3) and median OS was 2.9 years (95% CI 1.1 to 2.9). Serum proteomics showed a Veristrat good signature for all but one subject; this result changed to good following LAT. No signatures turned to poor at progression.
Conclusion:
LAT resulted in a modest extension in the duration of targeted therapy, supporting retrospective data in this population. Accrual to this study has been challenging due to the availability of 3[rd] generation EGFR TKIs and because LAT is often done outside of a clinical trial.
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P3.08 - Locally Advanced Nsclc (ID 724)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.08-004 - Phase I/II Trial of Nab-Paclitaxel or Paclitaxel Plus Carboplatin with Concurrent Radiation for Inoperable Stage IIIA/B NSCLC (ID 10220)
09:30 - 09:30 | Author(s): L.C. Villaruz
- Abstract
Background:
To determine the overall survival of Nab-Paclitaxel (Nab) or Paclitaxel (P) plus Carboplatin (C) with concurrent radiation therapy (RT) followed by consolidative chemotherapy (CT) with Nab-C or PC for patients (pts) with Stage IIIA/B Non-small cell lung cancer (NSCLC) when compared to historical controls and to assess for the safety of each regimen to guide further investigation
Method:
This phase I/II trial randomized 98 pts (6 pts phase I; 92 pts phase II). 75 pts were eligible for analysis on the phase II portion. For the phase I portion, weekly 50mg/m[2] of Nab and C AUC 2 was administered with concurrent thoracic RT (60-66 Gy) followed by CT comprising 100mg/m[2] Nab on days 1,8,15 (of a 21 day cycle) and C AUC 6 on day 1 for 2 cycles. For the randomized phase II portion, patients received either arm A) weekly 50mg/m[2] P and C AUC 2 or arm B) weekly 40mg/m[2] of Nab and C AUC 2 with concurrent RT followed by consolidative 200mg/m[2] P and C AUC 6 every three weeks for 2 cycles or 100mg/m[2] Nab on days 1,8,15 (of a 21 day cycle) and C AUC 6 on day 1 for 2 cycles. The primary end point was 2-year overall survival of 50% or greater.
Result:
Median follow up was 14.3 months. 2 patients experienced dose-limiting toxicities on the phase I portion as defined per protocol (grade 3 febrile neutropenia and grade 4 thrombocytopenia) leading to a dose reduction of concurrent Nab from 50mg/m[2 ]to 40mg/m[2] for the phase II portion. On the Phase II portion, Grade 3+ esophagitis was 3 and 2 pts, Grade 3+ pneumonitis was 3 and 5 pts and Grade 4+ hematological adverse events was 3 and 8 pts on A and B arms respectively. The 1- and 2-year overall survival rates for arm A and B were 80.6% (95%CI 63.4-90.3) and 69.2% (51.2-81.7); and 72.5% (48.4-86.8) and 56.5% (33.7-74.1) respectively. The 1- and 2-year progression free survival were 57.5% (38.7-72.5) and 46.1% (29.2-61.5); and 45.5% (24.7-64.3) and 20.7% (6.5-40.3) for arm A and B respectively.
Conclusion:
For pts with locally advanced Stage IIIA/B NSCLC, both arms A and B provided 2-year overall survival rates greater than 50%. The addition of Nab to chemoradiation was overall well tolerated, prompting potential interest going forward. Further analyses of quality of life measurements are currently underway. This project was supported by Celgene. Clinical Trial information: NCT01757288
