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A.F. Farago
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OA 07 - Biomarker for Lung Cancer (ID 659)
- Event: WCLC 2017
- Type: Oral
- Track: Biology/Pathology
- Presentations: 1
- Moderators:Philip Christopher Mack, Shinichi Toyooka
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 503
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OA 07.05 - Serial Biopsies in Patients with EGFR-Mutant NSCLC Highlight the Spatial and Temporal Heterogeneity of Resistance Mechanisms (ID 10181)
15:45 - 17:30 | Author(s): A.F. Farago
- Abstract
- Presentation
Background:
Resistance to EGFR tyrosine kinase inhibitors (TKIs) limits treatment outcomes among patients with EGFR-mutant NSCLC. Resistance mechanisms have previously been conceptualized as binary “positive/negative” variables, but emerging evidence suggests resistant cancers are heterogeneous, and subclones may be appreciated through multiple biopsies.
Method:
We retrospectively analyzed 221 EGFR mutant pts at MGH who had >1 biopsy after progression on their initial EGFR inhibitor. Data on acquired resistance (AR) mechanisms observed at each biopsy, adverse events, and treatment were collected.
Result:
Among 221 pts with a total of 355 post-AR tissue biopsies, median age was 59 (range, 28-88), 69% were female, 64% had EGFR del19, 33% L858R and 3% other activating mutations. Median number of biopsies per patient was 1 (range, 1-4). Biopsies at first resistance to EGFR TKI showed 61% T790M, 5% MET amplification (amp), 3% SCLC transformation, 2% acquired PIK3CA and 1% acquired BRAF mutations. 83 pts had two biopsies during their post-resistance course; 43/83 (52%) had heterogeneity between biopsy 1 and 2. In particular, 20% “lost” T790M, while 11% “gained” T790M. Among 17 pts who lost T790M, 3 gained a separate resistance mechanism, including MET amp and BRAF V600E. In some cases, synchronous biopsies identified spatial heterogeneity. For example, an osimertinib-resistant patient had a T790M/C797S lung nodule, while a concurrent mediastinal lymph node was wild-type at both loci (both sites retained the activating EGFR mutation). Similarly, another osimertinib-resistant patient with MET amp in a pleural effusion cell block had a lung nodule biopsy which lacked MET amp; the patient was treated with combination EGFR and MET inhibitors with a partial response. Additional details regarding concurrent liquid biopsies, treatment histories and clinical outcomes will be presented.
Conclusion:
In this large cohort of EGFR mutant NSCLC patients, we frequently observed variations in resistance mechanisms in patients with > 1 post-AR biopsy. Our data highlights the heterogeneity of resistant cancers and the limitations of a single biopsy in fully capturing the spectrum of resistance mechanisms in each patient. Serial biopsies or non-invasive methods may be required to characterize resistance and identify potential therapeutic targets.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-034 - Health Status in Patients with Small-Cell Lung Cancer Treated with Nivolumab Alone or Combined with Ipilimumab: CheckMate 032 (ID 9400)
09:30 - 16:00 | Author(s): A.F. Farago
- Abstract
Background:
CheckMate 032 (NCT01928394) is an open-label, phase 1/2 trial evaluating the efficacy and safety of nivolumab monotherapy and nivolumab plus ipilimumab in patients with advanced or metastatic solid tumors. In this study, nivolumab ± ipilimumab showed durable responses, encouraging survival, and manageable safety in patients with small-cell lung cancer (SCLC) that progressed after ≥1 previous platinum-containing regimens. An exploratory objective is to describe changes in patient-reported health status using the EuroQoL-5 Dimensions (EQ-5D) instrument.
Method:
The EQ-5D visual analog scale (VAS; scale: 0–100 [worst–best health]; minimally important difference [MID]=7) was assessed in the treatment period at baseline (week 1 prior to study drug administration) and then every 2 weeks in the nivolumab (3 mg/kg) arm and at baseline and then every 3 weeks in the nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) arm through week 13, and in both arms at subsequent tumor assessments (every 6 weeks until week 24 and every 12 weeks thereafter). After treatment discontinuation, the EQ-5D was assessed at follow-up visits 1 and 2, and at survival visits. EQ-5D VAS mean and mean within-patient change from baseline were estimated at each assessment. Time to first deterioration (TTD) in health status was also evaluated.
Result:
In the nivolumab (n=245) and nivolumab plus ipilimumab (n=156) arms, EQ-5D VAS completion rates were 90% and 85%, respectively, at baseline and remained ≥60% at the last assessment (≥5 patients/arm; weeks 97 and 121, respectively). Baseline mean EQ-5D VAS scores for the nivolumab and nivolumab plus ipilimumab arms were 67.1 and 65.2, respectively, scores similar to a lung cancer population norm (68). With monotherapy, EQ-5D VAS mean within-patient changes from baseline suggested health status stability while on treatment (estimated changes
Conclusion:
Preliminary EQ-5D VAS results from CheckMate 032 showed that on-treatment health status in patients with recurrent SCLC remained stable with nivolumab and improved (ie, increases in scores exceeded the MID) with nivolumab plus ipilimumab. For patients remaining on treatment for ≥6 months, mean EQ-VAS scores in both arms trended towards the population norm.
