A breakthrough in 40 years!

Globally, esophageal cancer is the fifth leading cause of cancer deaths

However, the first-line treatment of metastatic esophageal cancer has made little progress in the past 40 years, and fluoropyrimidine combined with platinum-based chemotherapy has been the mainstay

Today, this situation will be broken

The results of KEYNOTE-590 were published today in the latest issue of The Lancet

▲Professor Shen Lin, deputy dean of Peking University Cancer Hospital, is also one of the authors of this blockbuster research paper (screenshot source: The Lancet)

KEYNOTE-590 is a randomized, placebo-controlled, double-blind, phase 3 study conducted in 168 medical centers in 26 countries, recruiting untreated locally advanced, unresectable or metastatic esophageal cancer or Siewert type 1 Adult patients with gastroesophageal junction cancer (not limited to PD-L1 status)

As of the first interim analysis, the median follow-up time was 22.

Prolong overall survival (12.

Delay recurrence, prolong progression-free survival (6.

The 24-month overall survival rate is higher (28% vs 16%)

Pembrolizumab combined with chemotherapy had a higher objective response rate (45.

Moreover, further analysis of the data shows that patients with different characteristics can also benefit from pembrolizumab combined with chemotherapy.

CPS (Combined Positive Score): Reflects the expression level of PD-L1 protein in tumor samples

Patients with esophageal squamous cell carcinoma and PD-L1 CPS≥10 have a 43% lower risk of death (median overall survival time of 13.

For patients with esophageal squamous cell carcinoma, the risk of death was reduced by 28% (median overall survival time of 12.

For patients with PD-L1 CPS ≥ 10, the risk of death is reduced by 38% (median overall survival is 13.

▲Patients with different characteristics, receiving pembrolizumab combined with chemotherapy (blue line), have a longer overall survival

In adenocarcinoma patients, the overall survival benefit trend is also consistent, although it is not statistically significant
.
At the same time, the progression-free survival of patients with adenocarcinoma was significantly prolonged (median 6.
3 months vs 5.
7 months), and the risk of recurrence or death was reduced by 37%
.
A review article in the same period of The Lancet pointed out that this subgroup analysis was limited by a small sample size
.

It is worth noting that KEYNOTE-590 includes a diverse global population.
These data can be applied to patients worldwide, and a greater survival benefit (36% reduction in the risk of death) was observed in Asian patients
.
This is also consistent with this finding and the data of other previous studies.
Patients with esophageal cancer in Asia usually have squamous cell carcinoma histologically, and they benefit more significantly than non-Asian patients after receiving immune checkpoint inhibitor therapy
.

The paper pointed out that overall, the survival data of the pembrolizumab combined with chemotherapy group opened a gap with the chemotherapy group in the early treatment period, and continued to maintain the survival advantage over time
.
This overall survival benefit is also supported by the progression-free survival advantage of multiple subgroups.
At 12 and 18 months, the progression-free survival rate of pembrolizumab combined with chemotherapy is always higher
.
Moreover, the proportion of patients receiving similar follow-up anti-cancer treatments in the two study groups is similar (45% vs 48%), which indicates that the overall survival benefit of pembrolizumab combined with chemotherapy is not confounded by subsequent anti-cancer treatments.

.

The safety of pembrolizumab combined with chemotherapy is controllable.
Compared with chemotherapy alone, there is no new safety signal report
.
266 patients (72%) had treatment-related adverse events ≥3 grade, and 250 patients (68%) in the chemotherapy group
.

Based on this pivotal study, earlier this year, the US FDA has approved the first-line treatment of pembrolizumab in combination with chemotherapy for patients with locally advanced or metastatic esophageal cancer or gastroesophageal junction cancer
.
In China, pembrolizumab has previously been approved as a second-line treatment for patients with esophageal cancer
.