The world's first first-line treatment of esophageal cancer PD-1 was born!

Recently, the U.
S.
Food and Drug Administration (FDA) approved the PD-1 immune checkpoint inhibitor pembrolizumab combined with platinum-containing chemotherapy for the first-line treatment of unresectable or locally advanced or metastatic esophageal cancer that is not suitable for radical radiotherapy or chemotherapy.
Gastroesophageal junction cancer, regardless of PD-L1 expression.

This is the 29th indication that Pembrolizumab (commonly known as K drug in China) has been approved in the United States.
It is also the first and only PD-1 immune checkpoint inhibitor approved for the first-line treatment of esophageal cancer in the world.

This approval is based on the results of a global multi-center, randomized, double-blind controlled Phase III clinical study (KEYNOTE-590).

The analysis results of the study with a median follow-up of 10.
8 months were announced at the 2020 European Medical Oncology (ESMO) Congress.

The results of the study showed that whether it is in intention to treat (ITT), esophageal squamous cell carcinoma (ESCC), or PD-L1 CPS ≥ 10 ITT and ESCC population, K drug combined with platinum-based chemotherapy (cisplatin and 5-fluorouracil ) The overall survival (OS), disease progression-free survival (PFS), tumor objective response rate (ORR) and duration of response (DOR) data of first-line treatment all show significant superiority compared to the first-line treatment of platinum-containing chemotherapy , The safety data are comparable to standard chemotherapy.

Set a fixed width and height background on the fixed layout toolbar, which can be set to be included, can perfectly align the background image and text, and make your own template.
K drug significantly prolongs the survival time and breaks the ice.
The first-line esophageal cancer treatment will usher in a major turning point in 30 years.
Tumors with a very high fatality rate.

According to the Global Cancer (GLOBOCAN) statistical report released by the International Agency for Research on Cancer of the World Health Organization, the number of new cases of esophageal cancer worldwide in 2020 will be 604,100, and the number of deaths will be 544,076.

Early symptoms of esophageal cancer are not obvious, and about 70% of newly diagnosed patients have developed locally advanced; and in operable esophageal cancer, 50%-60% of patients will relapse or have distant metastases after surgery.

However, the treatment of metastatic esophageal cancer has been slowly developed in the past 30 years.
The first-line treatment is still mainly 5-FU, or paclitaxel combined with platinum-containing chemotherapy, with low effective rate, and the median overall survival (OS) is only a few months.
One year.

The results of the interim analysis of KEYNOTE-590 showed that in the first-line treatment of patients with locally advanced and metastatic esophageal cancer, pembrolizumab combined with chemotherapy compared with conventional chemotherapy has brought benefits to the entire population, significantly improved overall survival, and reduced The risk of death from disease is 27%, and the safety is controllable.

Whether in the ITT population, ESCC, or ITT and ESCC population with PD-L1 CPS ≥ 10, drug K combined with chemotherapy can bring statistically significant OS benefits compared to platinum-containing chemotherapy as the first-line treatment.
The OS was more than one year old; ESCC with PD-L1 CPS ≥ 10 and OS of the overall population benefited more significantly, with a median OS of 13.
9 months (8.
8 months in the control group) and 13.
5 months (9.
4 months in the control group) ), the risk of death was reduced by 43% and 38%, respectively.

KEYNOTE-590: OS of the overall population, ESCC, PD-L1 CPS ≥10, and ESCC population.
In view of the dazzling data of KENOTE-590, the US FDA only took 94 days to approve drug K combined with chemotherapy for the first-line treatment of esophageal cancer Indications.

High ORR increases the possibility of cure.
In the KEYNOTE-590 study, the ORR (RECIST v1.
1) evaluated by the investigator of the K drug + chemotherapy regimen reached 45.
0%, which increased the ORR (29.
3%) of the chemotherapy group by 54% (P<0.
0001) ).

At 24 months, the number of tumors in continuous remission was three times that of the chemotherapy group.

KEYNOTE-590: The ORR of the overall population and the ORR of DOR of 45% means that nearly half of the patients’ tumors can be reduced by 30% according to imaging evaluation.
This is a very important improvement, because high ORR predicts a better prognosis for treatment Patients with high tumor burden bring efficacy and confidence; at the same time, high ORR means that the tumor may be downgraded, thereby increasing the probability of surgical resection.
Surgical resection is still one of the best long-term survival benefits or even cures for patients with esophageal cancer.
The main means.

In addition, high ORR also laid the foundation for PD-1 combined chemotherapy for neoadjuvant therapy.

Although the five-year survival rate brought by surgical resection reaches 50%, half of the patients will still relapse.

Preoperative neoadjuvant therapy to achieve major pathological remission (MPR) or even complete pathological remission (pCR) is of great significance for reducing recurrence.

High ORR is a necessary prerequisite for improving the effectiveness of neoadjuvant therapy before surgery.

First-line whole population! Chinese esophageal cancer immunotherapy "co" can be unlimited.
Esophageal cancer is a high-incidence and idiopathic malignant tumor in China.

The data of the GLOBOCAN statistical report shows that in 2020, the number of new cases of esophageal cancer in my country is 324,422, and the death toll is 301,175, accounting for more than 50% of the global proportion.

Therefore, there is a huge unmet need for treatment of esophageal cancer, and there is a huge room for improvement in patient survival.

In June 2020, the National Medical Products Administration (NMPA) has approved K drug for the second-line treatment of locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) with CPS ≥ 10, which not only opens the era of immunotherapy for esophageal cancer treatment, but also “blows” The "Charge" of immunotherapy to enter the neoadjuvant, auxiliary and unresectable locally advanced esophageal cancer first-line treatment, a large number of clinical research and translational research for Chinese patients with esophageal cancer have sprung up.

What is exciting is that the indications of K drug combined with platinum-containing chemotherapy for the first-line treatment of unresectable locally advanced or metastatic esophageal cancer have been submitted to my country's NMPA and accepted in November 2020, and it is expected to be approved this year.

At that time, the first-line immunotherapy for unresectable locally advanced or metastatic esophageal cancer does not require PD-L1 detection.

It is believed that this treatment for the whole population will benefit more patients with esophageal cancer, and advance the treatment to the initial treatment stage where the patient's physical condition is better and the patient is more likely to benefit from long-term survival, and will have a more positive impact on subsequent treatment.

Undoubtedly, the US FDA, as a global drug review agency, approved the first-line treatment of esophageal cancer with K drug this time.
It is bound to fuel domestic esophageal cancer immunotherapy research, and for esophageal cancer-whether it is operable or inoperable esophageal cancer immunotherapy clinical practice Infuse great confidence.