Table 2:
Summary of efficacy in the intention-to-treat population
| Pembrolizumab 2 mg/kg (n=180) | Pembrolizumab 10 mg/kg (n=181) | Chemotherapy control (n=179) | |
|---|---|---|---|
| Progression-free survival assessed per RECIST v1.1, by independent central review | |||
| Number of events* | 129 (72%) | 126 (70%) | 155 (87%) |
| Median duration (months) | 2·9 (2·8–3·8) | 2·9 (2·8–4·7) | 2·7 (2·5–2·8) |
| Proportion progression free at 6 months | 34% (27–41) | 38% (31–45) | 16% (10–22) |
| Proportion progression free at 9 months | 24% (17–31) | 29% (23–37) | 8% (4–14) |
| Restricted mean duration based on 12 months of follow-up (months; post-hoc analysis) | 5·4 (4·7–6·0) | 5·8 (5·1–6·4) | 3·6 (3·2–4·1) |
| HR for death or disease progression,† pembrolizumab vs chemotherapy | 0·57 (0·45–0·73); p<0·0001‡ | 0·50 (0·39–0·64); p<0·0001‡ | Ref |
| HR for death or disease progression,† pembrolizumab 10 mg/kg vs 2 mg/kg | Ref | 0·91 (0·71–1·16)§ | ·· |
| Progression-free survival assessed per RECIST v1.1, by investigator review | |||
| Number of events* | 122 (68%) | 112 (62%) | 157 (88%) |
| Median duration (months) | 3·7 (2·9–5·4) | 5·4 (3·8–6·8) | 2·6 (2·4–2·8) |
| Proportion progression free at 6 months | 39% (32–46) | 45% (37–52) | 15% (10–21) |
| Proportion progression free at 9 months | 32% (25–40) | 36% (29–44) | 10% (6–15) |
| Restricted mean duration based on 12 months of follow-up (months; post-hoc analysis) | 5·8 (5·2–6·4) | 6·5 (5·8–7·1) | 3·7 (3·2–4·1) |
| HR for death or disease progression,† pembrolizumab vs chemotherapy | 0·49 (0·38–0·62); p<0·0001‡ | 0·41 (0·32–0·52); p<0·0001‡ | Ref |
| HR for death or disease progression,† pembrolizumab 10 mg/kg vs 2 mg/kg | Ref | 0·81 (0·63–1·05); p=0·12¶ | ·· |
| Progression-free survival assessed per modified RECIST v1.1, by investigator review | |||
| Number of events | 117 (65%) | 108 (60%) | 154 (86%) |
| Median duration (months) | 4·2 (3·1–6·2) | 5·6 (4·2–7·7) | 2·6 (2·5–2·8) |
| Proportion progression free at 6 months | 43% (35–50) | 48% (40–55) | 17% (12–23) |
| Proportion progression free at 9 months | 35% (27–43) | 38% (30–46) | 10% (6–16) |
| HR for death or disease progression,† pembrolizumab vs chemotherapy | 0·45 (0·35–0·.57); p<0·0001‡ | 0·39 (0·30–0·51); p<0·0001‡ | Ref |
| HR for death or disease progression,† pembrolizumab 10 mg/kg vs 2 mg/kg | Ref | 0·82 (0·63–1·07); p=0·15¶ | ·· |
| Best overall response assessed per RECIST v1.1, by independent central review | |||
| Complete response | 4 (2%) | 5 (3%) | 0 |
| Partial response | 34 (19%) | 41 (23%) | 8 (4%) |
| Stable disease | 32 (18%) | 31 (17%) | 33 (18%) |
| Progressive disease | 84 (47%) | 86 (48%) | 111 (62%) |
| Not evaluable|| | 26**(14%) | 18 (10%) | 27 (15%) |
| Overall response assessed per RECIST v1.1, by independent central review | |||
| Number of patients who responded (% [95% CI]) | 38 (21% [15–28]) | 46 (25% [19–32]) | 8 (4%; [2–9]) |
| Difference in overall response,†† pembrolizumab vs control | 13% (7–21); p<0・0001 | 18% (11–27); p<0・0001 | Ref |
| Diff erence in overall response,†† pembrolizumab 10 mg/kg vs 2 mg/kg | Ref | 6% (–3 to 14); p=0・21¶ | ・・ |
| Duration of response | |||
| Median duration (weeks) | Not reached (25 to not reached) | Not reached (36 to not reached) | 37 (12–41) |
Data in parentheses are % or 95% CIs, unless otherwise indicated. ECOG=Eastern HR=hazard ratio. RECIST v1.1=Response Evaluation Criteria in Solid Tumors, version 1.1.
A breakdown of progression-free survival events is provided in the appendix.
HRs and associated 95% CIs were based on Cox regression models with treatment as a covariate stratified by ECOG performance status (0 vs 1), lactate dehydrogenase concentration (normal vs raised), and BRAFV600 status (mutant vs wild type).
One-sided p value on the log-rank test.
No p value available for the comparison of pembrolizumab doses because the study was not powered for such a comparison.
Nominal p value, not powered for hypothesis testing.
Accounts for patients who withdrew consent, were withdrawn by the investigator, died, or started new anticancer therapy before the first tumour assessment and therefore did not have response evaluated, or patients with tumour assessments, but overall response based on the scans was not evaluable.
Includes one patient with no disease.
Difference calculated based on Miettinen and Nurminen method covariate stratified by ECOG performance status (0 vs 1), lactate dehydrogenase concentration (normal vs raised), and BRAFV600 status (mutant vs wild type).