Article Figures & Data
Figures
- Figure 1.
Median PFS (A) and OS (B) in patients with metastatic pancreatic adenocarcinoma receiving 150 mg of GDC-0449 daily for 4 weeks followed by 150 mg GDC-0449 daily and 1,000 mg/m2 of gemcitabine on days 1, 8, and 15 every 28 days.
- Figure 2.
A, immunostaining for SHH shows high (>200) and low (≤200) SHH score in patients with pancreatic adenocarcinoma. B, trichrome staining shows decrease in fibrosis on repeat biopsy after 3 weeks of GDC-0449 monotherapy compared with baseline. C, pancreatic adenocarcinoma tissue from same patient immunostained for Ki-67 shows decrease in expression on repeat biopsy after 3 weeks of GDC-0449 monotherapy compared with baseline. The tissue was also stained with H&E to assess for morphology.
Tables
- Table 1.
Demographics and baseline characteristics
Total patients enrolled (N = 25) Variable Patients, n % Age, y Median 65 Range 46–80 Sex Male 15 60 Female 10 40 ECOG performance status 0 16 64 1 9 36 Race Caucasian 24 96 African American 1 4 Histology Adenocarcinoma 24 96 Acinar 1 4 Location of biopsy Liver metastasis 17 68 Primary pancreatic mass 4 16 Omental metastasis 2 8 Other (perihepatic mass, neck lymph node) 2 8 Serum CA 19-9 Median, U/mL 3211 Range, U/mL 4–429,939 >150 U/mL 18 72 Biopsy Baseline 25 100 At 3 wks 23 92 - Table 2.
Summary of efficacy
Variable No. of Patients % Number of evaluable patients 25 PFS At 3 mo 10 40 Median, mo 2.8 95% CI, mo 1.4–4.7 OS Median, mo 5.3 Range, mo 3.6–8.4 Evaluable patients, n 23 Radiologic response, after 4 wks on GDC-0449 alone Complete response 0 0 Partial response 0 0 Stable disease 14 60.9 Progressive disease 9 39.1 Objective response rate 0 0 Radiologic response, best overall Complete response 0 0 Partial response 5 21.7 Stable disease 10 43.5 Progressive disease 8 34.8 Objective response rate 5 21.7 CA 19-9 response, after 4 wks on GDC-0449 alone Evaluable patientsa,n 20 87 >20% decrease 0 0 ≤20% decrease 1 5 Primary increase 19 95 CA 19-9 response, best overall Evaluable patientsa, n 19 82.6 >50% decrease 6 31.6 ≤50% decrease 2 10.5 Primary increase 11 57.9 -
↵aNumber of patients is less than the 23 (= overall evaluable patients) due to normal values throughout course of therapy (n = 3) and missing values at follow-up (n = 1).
-
- Table 3.
Impact of clinical and correlative variables on overall survival
Evaluable patients (N = 23) Variable No. of patientsa HR 95% CI P Age >65 y 9 2.72 0.98–7.58 0.05 ≤65 y 14 Gender Male 14 0.63 0.25–1.60 0.33 Female 9 Baseline CA 19-9 >1,000 U/mL 15 2.15 0.82–5.63 0.12 ≤1,000 U/mL 8 Baseline SHH >200 12 0.76 0.29–1.99 0.76 ≤200 8 Baseline Ki-67 >30% 13 0.68 0.26–1.79 0.43 ≤30% 7 Baseline GLI1 >0.5 9 1.01 0.42–2.46 0.98 ≤0.5 14 Baseline PTCH1 >2.0 11 0.79 0.33–1.89 0.60 ≤2.0 12 Baseline fibrosis >50% 14 0.44 0.18–1.10 0.08 ≤50% 9 Baseline CSCs >5% 9 0.75 0.30–1.86 0.54 ≤5% 13 Change in Ki-67, after 3 wks Decrease 9 0.87 0.32–2.35 0.79 Increase 8 Change in GLI1, after 3 wks >75% decrease 15 0.85 0.32–2.26 0.74 ≤75% decrease, or increase 6 Change in PTCH1, after 3 wks Decrease 19 0.79 0.26–2.39 0.68 Increase 4 Change in fibrosis, after 3 wks Decrease 10 1.07 0.44–2.61 0.89 Increase 12 Change in CSCs, after 3 wks Decrease 11 0.62 0.24–1.60 0.32 Increase 10 CA 19-9 response, best overall >50% decrease 6 0.13 0.03–0.60 0.01 ≤50% decrease, or increase 13 -
↵aNumber of patients may be less if both pretreatment and posttreatment samples were not available.
-
- Table 4.
Summary of correlative studies
Evaluable patients (N = 23) Relative change in variable between baseline and repeat biopsy after 3 weeks on GDC-0449 Patients, n % Ki-67 index, IHC Evaluable patients, n 17 68 >20% decrease 3 17.65 ≤20% decrease 6 35.29 Increase 8 47.06 Median −1.07 CSCs,% FACS Evaluable patients, n 21 84 >20% decrease 10 47.62 ≤20% decrease 1 4.76 Increase 10 47.62 Median −16.08 Fibrosis, trichrome Evaluable patients, n 22 88 >50% decrease 3 13.64 0–50% decrease 7 31.82 Increase 12 54.54 Median 0 GLI1, qRT-PCR Evaluable patients, n 23 100 >50% decrease 19 82.61 0–50% decrease 3 13.04 Increase 1 4.35 Median −93 PTCH1, qRT-PCR Evaluable patients, n 23 100 >50% decrease 9 39.13 ≤50% decrease 10 43.48 Increase 4 17.39 Median −38
Supplementary Data
Files in this Data Supplement:
- Supplementary Figure 1 Legend - Supplementary Figure 1 Legend. Median overall survival correlated with change in CA 19-9 (>50% decrease, versus {less than or equal to}50% decrease, or primary increase)
- Supplementary Figure 1 - Supplementary Figure 1. Median overall survival correlated with change in CA 19-9 (>50% decrease, versus {less than or equal to}50% decrease, or primary increase) compared to baseline.
- Supplementary Table 1 - Supplementary Table 1. Summary of Treatment-Related Adverse Events
Volume 20, Issue 23
