Use of Early Tumor Shrinkage To Predict Long-term Outcome in Metastatic

Transcription

1 Use of Early Tumor Shrinkage To Predict Long-term Outcome in Metastatic Colorectal Cancer Treated With Cetuximab Piessevaux et al Data Supplement 2 LANDMARK ANALYSIS OF THE CRYSTAL AND OPUS STUDIES An analysis in which PFS and OS have been calculated from the landmark (first radiological evaluation, week 8) for the selected cutoffs ( 20%, <10% 10 40% and >40%) in patients with KRAS wild-type or KRAS mutant tumors. Page 1 of 20

2 Early tumor shrinkage (ETS) <20% vs 20% DS2 Table S1. Impact of ETS (<20% or 20%) on PFS and Survival in the CRYSTAL and OPUS Trials using the Landmark Analysis Parameter CRYSTAL OPUS < 20% 20% < 20% 20% Progression-free Chemotherapy + cetuximab KRAS wild-type, n Median, months % CI 4.2 to to to to 14.0 HR* % CI 0.23 to to 0.46 P value <0.001 <0.001 KRAS mutant, n Median, months % CI 3.6 to to to to 6.7 HR* % CI 0.39 to to 0.76 P value Chemotherapy alone KRAS wild-type, n Median, months % CI 5.2 to to to to 6.6 HR* % CI 0.43 to to 1.53 P value <0.001 NS KRAS mutant, n Median, months % CI 5.1 to to to to 8.3 HR* % CI 0.58 to to 2.32 P value NS NS Survival Chemotherapy + cetuximab KRAS wild-type, n Median, months % CI 13.6 to to to to 27.5 HR* % CI 0.40 to to 0.79 P value < KRAS mutant, n Median, months % CI 11.3 to to to to 18.8 HR* % CI 0.46 to to 1.39 P value NS Chemotherapy alone KRAS wild-type, n Median, months % CI 13.5 to to to to 23.2 HR* % CI 0.56 to to 1.46 P value NS Page 2 of 20

3 KRAS mutant, n Median, months % CI 12.1 to to to to 24.8 HR* % CI 0.63 to to 2.36 P value NS NS Abbreviations: CI, confidence interval; HR, hazard ratio; NS, not significant. *HR obtained from a univariate Cox proportional hazards model with treatment as single covariate and Eastern Cooperative Oncology Group performance status (0, 1 v 2) as stratum. Page 3 of 20

4 DS2 Fig S1. Kaplan-Meier curves for PFS and survival using the landmark analysis in relation to ETS (cutoff 20% at week 8) according to clinical trial in patients with KRAS wild-type tumors. CRYSTAL study PFS KRAS WT / FOLFIRI + cetuximab N of Censored W8_20_INV Total N Events N Percent <20% % 20% % Overall % a KRAS WT/Treatment group (as randomized) = FOLFIRI + cetuximab. Time (months) <20% 20% Page 4 of 20

5 KRAS WT / FOLFIRI W8_20_INV Total N N of Events Time (months) <20% 20% N Censored Percent < 20% % 20% % Overall % a KRAS WT/Treatment group (as randomized) = FOLFIRI. Page 5 of 20

6 OS KRAS WT / FOLFIRI + cetuximab W8_20_INV Total N N of Events N Censored Percent < 20% % >20% % Overall % a KRAS WT/Treatment group (as randomized) = FOLFIRI + cetuximab. Time (months) <20% Page 6 of 20

7 KRAS WT / FOLFIRI N of Censored W8_20_INV Total N Events N Percent < 20% % 20% % Overall % a KRAS WT/Treatment group (as randomized) = FOLFIRI. Time (months) <20% 20% Page 7 of 20

8 OPUS study PFS KRAS WT / FOLFOX4 + cetuximab Radiological decrease N of Censored at week 8 Total N Events N Percent <20% % 20% % Overall % a KRAS WT/Treatment group (as randomized IVRS) = FOLFOX4 + cetuximab. Time (months) <20% 20% Page 8 of 20

9 KRAS WT / FOLFOX4 Radiological decrease N of Censored at week 8 Total N Events N Percent <20% % 20% % Overall % a KRAS WT/Treatment group (as randomized IVRS) = FOLFOX4. Time (months) <20% 20% Page 9 of 20

10 OS KRAS WT / FOLFOX4 + cetuximab Radiological decrease N of Censored at week 8 Total N Events N Percent <20% % 20% % Overall % a KRAS WT/Treatment group (as randomized IVRS) = FOLFOX4 + cetuximab. Time (months) <20% 20% Page 10 of 20

11 KRAS WT / FOLFOX4 Radiological decrease N of Censored at week 8 Total N Events N Percent <20% % 20% % Overall % a KRAS WT/Treatment group (as randomized IVRS) = FOLFOX4. Time (months) <20% 20% Page 11 of 20

12 Early tumor shrinkage (ETS) <10%, 10 40%, >40% DS2 Table S2. Impact of ETS (<10% or 10-40% or >40%) on PFS and Survival in the CRYSTAL and OPUS Trials using the Landmark Analysis Parameter CRYSTAL OPUS < 10% 10 40% > 40% < 10% 10 40% > 40% Progression-free survival Chemotherapy + cetuximab KRAS wild-type Median, months 95% CI KRAS mutant Median, months 95% CI Chemotherapy alone KRAS wild-type Median, months 95% CI KRAS mutant Median, months 95% CI Survival Chemotherapy + cetuximab KRAS wild-type Median, months 95% CI KRAS mutant Median, months 95% CI Chemotherapy alone KRAS wild-type Median, months 95% CI KRAS mutant Median, months 95% CI Abbreviation: CI, confidence interval to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to to 29.9 Page 12 of 20

13 DS2 Fig S2 Kaplan-Meier curves for PFS and survival using the landmark analysis in relation to early tumor shrinkage (cutoffs of <10, 10-40% and >40% at week 8 in patients with KRAS wild-type tumors. CRYSTAL study PFS KRAS WT/ FOLFIRI + cetuximab Relative change of the Censored sum of the longest diameters at week 8 Total N N of Events N Percent <10% % 10-40% % >40% % Overall % a KRAS WT/Treatment group (as randomized) = FOLFIRI + cetuximab. Time in months >10% 10-40% >40% Page 13 of 20

14 KRAS WT/FOLFIRI Relative change of the sum of the longest diameters at week 8 Total N N of Events N Censored Percent <10% % 10-40% % >40% % Overall % a KRAS mutation status = KRAS WT/Treatment group (as randomized) = FOLFIRI. Time in months >10% 10-40% >40% Page 14 of 20

15 OS KRAS WT/ FOLFIRI + cetuximab Relative change of the sum of the longest diameters at week 8 Total N N of Events N Censored Percent <10% % 10-40% % >40% % Overall % a KRAS WT/ Treatment group (as randomized) = FOLFIRI + cetuximab. Time in months >10% 10-40% >40% Page 15 of 20

16 KRAS WT/ FOLFIRI Relative change of the Censored sum of the longest diameters at week 8 Total N N of Events N Percent <10% % 10-40% % >40% % Overall % a KRAS WT/Treatment group (as randomized) = FOLFIRI. Time in months >10% 10-40% >40% Page 16 of 20

17 OPUS study PFS KRAS WT/ FOLFOX4 + cetuximab Relative decrease of the Censored sum of the longest diameters at week 8 Total N N of Events N Percent <10% % 10-40% % >40% % Overall % a KRAS WT/ Treatment group (as randomized IVRS) = FOLFOX4 = cetuximab. Time in months >10% 10-40% >40% Page 17 of 20

18 KRAS WT/ FOLFOX4 Relative decrease of the Censored sum of the longest diameters at week 8 Total N N of Events N Percent <10% % 10-40% % >40% % Overall % a KRAS WT/ Treatment group (as randomized IVRS) = FOLFOX4. Time in months >10% 10-40% >40% Page 18 of 20

19 OS KRAS WT/ FOLFOX4 + cetuximab Relative decrease of the sum of the longest diameters at week 8 Total N N of Events N Censored Percent <10% % 10-40% % >40% % Overall % a KRAS WT/ Treatment group (as randomized IVRS) = cetuximab + FOLFOX4. Time in months >10% 10-40% >40% Page 19 of 20

20 KRAS WT/FOLFOX4 Relative decrease of the Censored sum of the longest diameters at week 8 Total N N of Events N Percent <10% % 10-40% % >40% % Overall % a KRAS WT/ Treatment group (as randomized IVRS) = FOLFOX4. Time in months >10% 10-40% >40% Page 20 of 20