图解ASCO19 day2 / 四六文摘

首先是3个LBA

KEYNOTE-001的5年更新

几个数值而已，已经过了激动的年龄了

还是自己画的图销魂，可以结合KEYNOTE-010比对下≥2L以上的部分，基本接近

KEYNOTE-062

KEYNOTE-062，GC的一线，一块难啃的骨头

先看P vs C，1）在 CPS≥1的群体中达到了非劣性的预设，而在CPS≥10的群体中Pembro带来了有临床意义的OS提升(17.4 mo vs 10.8 mo)；2）不管是CPS ≥1还是 ≥10的群体，OS曲线在前10个月有交叉，尤其在CPS≥10群体Pembro也要到2年的时候才会显示出对化疗的优势

然后看P+C vs C，CPS ≥1的图没找到，预计和 CPS≥10走势类似，都是达到非劣性

在这里，OS的非劣性说到底也就是遮羞布——接下来，GC的免疫治疗的研究重点会不会变成如何让免疫治疗在早期就起效，至少照搬NSCLC用化疗是行不通了

Bckground: KEYNOTE062 (NCT02494583) was a randomized, active controlled study of 1L P or P+C vs C in pts with PD-L1 combined positive score ≥1 (CPS ≥1), HER2-negative, advanced GC.

Methods: Eligible pts were randomized 1:1:1 to P 200 mg Q3W for up to 2 y, P+C (cisplatin 80 mg/m² + 5-FU 800 mg/m²/d on d1-d5 Q3W [or capecitabine 1000 mg/m² BID on d1-d14 Q3W per local guideline]) or placebo Q3W + C. Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary endpoints were OS in CPS ≥1 and CPS ≥10 for P+C vs C and P vs C and PFS (RECIST v1.1; central review) in CPS ≥1 for P+C vs C. ORR (RECIST v1.1; central review) in CPS ≥1 for P+C vs C was the secondary endpoint. Final analysis cutoff date was 26 Mar 2019.

Results: 763 pts (281 with CPS ≥10) were randomized to P+C (257), P (256), or C (250) (Table). Median follow-up was 11.3 mo. P was noninferior to C for OS in CPS ≥1 per prespecified margins. P vs C prolonged OS in CPS ≥10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but wasn’t tested per analysis plan. P+C vs C was not superior for OS in CPS ≥1 or CPS ≥10, with a favorable trend for P+C. P+C did not significantly prolong PFS in CPS ≥1. ORR was higher for P+C vs C. Grade 3-5 drug-related AE rates were 17% (P), 73% (P+C), and 69% (C).

Conclusions: As 1L therapy for advanced GC, P was noninferior to C for OS in CPS ≥1 with clinically meaningful improvement for OS in CPS ≥10. P+C did not show superior OS and PFS in CPS ≥1 and OS in CPS ≥10. The safety profile was more favorable for P vs C.

Clinical trial information: NCT02494583

MONALEESA-7

然后是MONALEESA-7 的OS数据更新，之前的PFS：

23·8 mo(95% CI 19·2–NR) vs 13·0 mo(11·0–16·4) (hazard ratio 0·55, 95% CI 0·44–0·69; p<0·0001)

这次OS的更新: NR vs 40.9 mo; HR, 0.712 [95% CI, 0.54-0.95]; p = 0.00973，首次证明相比内分泌，CDK4/6i + 内分泌能显著延长OS

亮点在于全靠同行衬托：Palbociclib+leteozole可是只提升PFS未能改善OS

Background: The phase III MONALEESA-7 study (NCT02278120) is the first dedicated trial of endocrine therapy (ET) ± a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in premenopausal patients (pts) with hormone receptor–positive (HR+)/HER2− ABC. The study met its primary endpoint of significantly longer progression-free survival (PFS) with ribociclib (RIB; a CDK4/6 inhibitor) + ET vs placebo (PBO) + ET (median, 23.8 vs 13.0 mo; HR, 0.55; P< 0.0001; Tripathy D, et al. Lancet Oncol. 2018).

Methods: Premenopausal pts (N=672) with HR+/HER2− ABC were treated with RIB or PBO + goserelin and either a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole) or tamoxifen. This is the 2nd of 3 protocol-specified OS analyses (scheduled to occur after ≈ 189 deaths [75% of the planned total events]). OS was evaluated by Kaplan-Meier methods, and statistical comparison was made by 1-sided stratified log-rank test, with a protocol-defined Lan-DeMets (O’Brien-Fleming) stopping boundary of p < 0.01018 for superior efficacy.

Results: The data cutoff for this prespecified interim analysis was Nov 30, 2018, and the median follow-up was 34.6 mo (min, 28.0 mo). At cutoff, 173 pts were continuing study treatment (RIB, n=116; PBO, n=57), and OS was evaluated after 192 deaths (RIB, n=83; PBO, n=109). RIB + ET demonstrated a significantly longer OS than PBO + ET (median, not reached vs 40.9 mo [95% CI, 37.80 mo-not evaluable]; HR, 0.712 [95% CI, 0.54-0.95]; p = 0.00973). The result crossed the prespecified stopping boundary for superior efficacy. Estimated OS rates with RIB + ET vs PBO + ET at 42 mo were 70.2% vs 46.0%, respectively. In pts who received an NSAI (n=495), RIB + ET demonstrated a consistent OS improvement vs PBO + ET (HR, 0.699 [95% CI, 0.50-0.98]). Posttreatment therapy use was balanced between treatment arms (RIB, 68.9%; PBO, 73.2%).

Conclusions: RIB + ET demonstrated a clinically and statistically significant longer OS than ET alone in premenopausal pts with HR+/HER2− ABC. This is the first time that a CDK4/6 inhibitor or any targeted agent + ET has demonstrated significantly longer OS vs ET alone as initial endocrine-based therapy.

Clinical trial information: NCT02278120

然后看其他进展

EAGLE: Durva±Treme vs. SOC治疗含铂化疗后进展的 R/M HNSCC