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A. Ardizzoni
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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 - 09:30 | Author(s): A. Ardizzoni
- 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.
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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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P3.01-043 - Impact of ErbB Mutations on Clinical Outcomes in Afatinib- or Erlotinib-Treated Patients with SCC of the Lung (ID 9457)
09:30 - 09:30 | Author(s): A. Ardizzoni
- Abstract
Background:
In LUX-Lung 8 (LL8), second-line afatinib (an irreversible ErbB family blocker) significantly improved OS (median 7.9 versus 6.8 months; HR [95% CI]: 0.81 [0.69‒0.95]; p=0.0077), and PFS (2.6 versus 1.9 months; 0.81 [0.69‒0.96]; p=0.0103) versus erlotinib in lung SCC (N=795). Comprehensive genetic analysis in LL8 patients assessed whether afatinib efficacy varied according to genetic aberrations in cancer-related genes, including ErbB family mutations.
Method:
Tumor genetic analysis (TGA) was performed using Foundation Medicine FoundationOne™ next-generation sequencing (NGS). The cohort was enriched for patients with PFS >2 months, reflecting a range of responsiveness to EGFR-TKIs. EGFR expression was assessed by immunohistochemistry (IHC) in a largely separate cohort. Cox regression analysis correlated PFS/OS with genetic mutations (individual/grouped) and EGFR expression.
Result:
Of 440 patients selected for TGA (PFS >2 months: n=320; ≤2 months: n=120), samples from 245 were eligible (afatinib: n=132; erlotinib: n=113). In the selected TGA population, PFS/OS outcomes were improved in the afatinib versus erlotinib arm. Baseline characteristics were similar in TGA and IHC cohorts and LL8 overall. In the TGA subset, 53 patients (21.6%) had ≥1 ErbB family mutation (EGFR: 6.5%; HER2: 4.9%; HER3: 6.1%; HER4: 5.7%). Beyond the benefit seen for afatinib in the overall population, in afatinib-treated patients, PFS/OS were longer when ErbB mutations were present (PFS: 4.9 versus 3.0 months; OS: 10.6 versus 8.1 months). Conversely, survival outcomes in erlotinib-treated patients were similar with/without ErbB mutations. Presence of HER2 mutations predicted favorable PFS/OS with afatinib versus erlotinib. The Table shows outcomes in patients with/without ErbB family mutations, and by EGFR expression levels (afatinib: n=157; erlotinib: n=188).
Conclusion:
These data are provocative and suggest that NGS may enable identification of lung SCC patients who would derive additional clinical benefit from afatinib. Differential outcomes with respect to ErbB mutations for afatinib and erlotinib are hypothesized to reflect afatinib’s broader mechanism of action.Subgroup n Afatinib vs erlotinib PFS OS HR (95% CI) p~interaction~ HR (95% CI) p~interaction~ ErbB mutation-positive ErbB mutation-negative 53 192 0.56 (0.29–1.08) 0.70 (0.50–0.97) 0.718 0.62 (0.35‒1.12) 0.76 (0.56‒1.03) 0.683 EGFR mutation-positive EGFR mutation-negative 16 229 0.64 (0.17–2.44) 0.67 (0.50–0.91) 0.981 1.01 (0.32–3.16) 0.72 (0.54–0.95) 0.529 HER2 mutation-positive HER2 mutation-negative 12 233 0.06 (0.01–0.59) 0.72 (0.54–0.97) 0.006 0.06 (0.01–0.57) 0.76 (0.58–1.00) 0.004 HER3 mutation-positive HER3 mutation-negative 15 230 0.52 (0.16–1.72) 0.69 (0.51–0.94) 0.692 0.84 (0.27–2.59) 0.73 (0.56–0.97) 0.998 HER4 mutation-positive HER4 mutation-negative 14 231 0.21 (0.02–1.94) 0.67 (0.50–0.91) 0.909 0.22 (0.05–1.04) 0.75 (0.56–0.99) 0.272 EGFR IHC positive EGFR IHC negative 292 53 0.74 (0.56–0.97) 0.76 (0.41–1.40) 0.985 0.82 (0.63–1.06) 0.75 (0.41–1.40) 0.882 EGFR amplification present EGFR amplification absent 17 228 0.72 (0.18–2.90) 0.68 (0.50–0.92) 0.994 0.50 (0.15–1.65) 0.76 (0.58–1.00) 0.413 HER2 amplification present HER2 amplification absent 9 236 0.94 (0.20–4.38) 0.68 (0.50–0.91) 0.861 1.10 (0.27–4.48) 0.72 (0.54–0.94) 0.388
