Drug K approved for first-line treatment of esophageal cancer

*It is only for medical professionals to read.
The high ORR of K drug combined with chemotherapy brings unlimited possibilities for operable esophageal cancer immunotherapy.

 On March 24, 2021, the U.
S.
Food and Drug Administration (FDA) approved the immune checkpoint inhibitor pembrolizumab (PD-1 inhibitor) combined with platinum-containing chemotherapy for the first-line treatment of unresectable or unsuitable radical radiotherapy and chemotherapy Locally advanced or metastatic esophageal cancer or 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 Society of 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 (5-FU)] 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 that it is significantly more significant than the first-line treatment of platinum-containing chemotherapy The superiority and safety data are comparable to standard chemotherapy.

K drug first-line ice-breaking esophageal cancer treatment is turning point.
Esophageal cancer is a tumor with a high degree of malignancy and a very high mortality 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 developed slowly in the past 30 years.
The first-line treatment is still based on 5-FU or paclitaxel combined with platinum-containing chemotherapy, which has a low effective rate.
The median OS is only a few months, less than a year.

 The results of the interim analysis of KEYNOTE-590 showed that in the first-line patients with locally advanced and metastatic esophageal cancer, pembrolizumab combined with chemotherapy has brought benefits to the entire population, with a significant increase in OS and a reduction of 27%.
The risk of death from disease is controllable in safety.

 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 with first-line platinum-based chemotherapy, and the median OS is more than one year; ESCC with PD-L1 CPS ≥ 10 and OS in the overall population have more obvious benefits, 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 the 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) assessed 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.

All the crowd on the front line! Drug K leads the immunotherapy of esophageal cancer with unlimited possibilities.
Esophageal cancer is a malignant tumor with high incidence and idiopathic incidence in China.

The GLOBOCAN statistics report shows that in 2020, the number of new cases of esophageal cancer in my country is 324,422, and the number of deaths 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) approved K drug for the second-line treatment of locally advanced or metastatic ESCC with CPS ≥ 10, which not only opened the era of immunotherapy for the treatment of esophageal cancer, but also "sounded" immunotherapy.
The "Charge", a new adjuvant, auxiliary, and first-line treatment for unresectable locally advanced esophageal cancer, has sprung up a large number of clinical and translational studies on Chinese patients with esophageal cancer.

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

By then, the first-line immunotherapy for unresectable locally advanced or metastatic esophageal cancer does not require PD-L1 detection, which is expected to benefit more patients with esophageal cancer; at the same time, immunotherapy will be promoted to patients with better physical conditions and more likely to benefit from long-term survival.
In the initial treatment stage, it has 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, which is bound to fuel domestic esophageal cancer immunotherapy research, and for esophageal cancer-whether it is operable or inoperable esophageal cancer immunotherapy clinical Practice injects great confidence.