3-year OS rate 61% KEYNOTE-177 OS analysis results "shown" ASCO

At the American Society of Clinical Oncology (ASCO) annual meeting a year ago, the analysis results of the Phase III clinical study KEYNOTE-177 were first published in the form of LBA (Late-breaking Abstract) and caused a sensation1
.

Less than a month later (June 29, 2020), the U.
S.
Food and Drug Administration (FDA) approved the PD-1 immune checkpoint inhibitor Pabolizol based on the positive results of the progression-free survival (PFS) in the study Monoclonal antibody (K drug) is the first-line treatment for unresectable or metastatic colorectal cancer (mCRC) of MSI-H/dMMR
.

Today, at the 2021 ASCO conference, the overall survival (OS) analysis results of the KEYNOTE-177 study were officially announced in the form of an oral report.
The 36-month OS rate of K-drug single-agent first-line treatment reached 61%
.

Currently, K drug alone has become the new standard for the first-line treatment of unresectable or metastatic MSI-H/dMMR colorectal cancer
.

KEYNOTE-177 not only rewrites the National Comprehensive Cancer Network (NCCN) Colorectal Cancer Diagnosis and Treatment Guidelines, but also has been recommended by Level I experts in the newly released 2021 Chinese Society of Clinical Oncology (CSCO) Colorectal Cancer Diagnosis and Treatment Guidelines in China
.

Nevertheless, another primary endpoint of the KEYNOTE-177 study-whether positive results can also be obtained for OS is still interesting, and the focus is not only on whether the median OS is improved, but also the 3 years or 4 years of K-drug single-agent first-line treatment.
Is the annual OS rate enough "stunning"
.

KEYNOTE-177 is a phase III clinical study aimed at evaluating K-drug monotherapy versus standard therapy (FOLFOX or FOLFIRI chemotherapy ± targeted bevacizumab or cetuximab) for the first-line treatment of MSI-H mCRC1
.

The main endpoints of the study were PFS and OS assessed by RECIST
.

Secondary endpoints included objective response rate (ORR) and safety assessed by RECIST v1.
1
.

According to the final OS data analysis result of KEYNOTE-177 officially announced by ASCO today2, the median follow-up was over 44 months (44.
5 [36.
0-60.
3] months in the K drug treatment group, 44.
4 [36.
2-58.
6] months in the control group) 60% of patients in the control group received PD-1/PD-L1 immune checkpoint inhibitor treatment after disease progression; the median OS of the K drug group had not yet reached, and the median OS of the control group was 36.
7 months and died The risk was reduced by 26% (HR 0.
74; 95% CI, 0.
53-1.
03; P=0.
0359); the K drug treatment group showed a trend of OS benefit, the 36-month OS rate was 61%, and the control group was 50%
.

KEYNOTE-177 Final OS analysis results 2 Previous studies have shown that the OS of FOLFOX or FOLFIRI chemotherapy ± targeted bevacizumab or cetuximab for advanced colorectal cancer is 21.
5 months 3
.

The median OS of the KEYNOTE-177 control group reached 36.
7 months, which was much higher than the OS results of previous studies, suggesting that the OS benefits of second-line immunotherapy for the control group largely "covered" the K drug first-line treatment zone The advantage of coming OS
.

The summary of this release also updated the data analysis results of PFS, and secondary endpoints such as ORR and safety 2: The median PFS of the K drug group was 16.
5 months, which was twice that of the control chemotherapy group (8.
2 months) (HR =0.
59; 95%CI: 0.
45~0.
79; P=0.
0002); the final ORR of the K drug group was 45.
1% (20 CR, 49 PR), and the control group was 33.
1% (6 CR, 45 PR); K drug group The median duration of response (DOR) did not reach (2.
3+ ~ 53.
5+), and the control group was 10.
6 months (2.
8 ~ 48.
3+); the incidence of treatment-related adverse events (TRAE) above grade 3 in the K drug group was 21.
6% , The control group was 66.
4%
.

 Although the high proportion of second-line immunotherapy in the control group led to the K drug group only showing a trend of OS benefit, but failed to reach statistical significance, 61% of patients still survived at 36 months, and they were still better than the control group This is 11 percentage points higher, which brings solid evidence-based medical evidence for K drug as a standard first-line treatment for MSI-H/dMMR advanced colorectal cancer
.

Although there are currently multiple PD-(L)1 immune checkpoint inhibitors approved globally and domestically, there are few long-term OS follow-up data for patients with advanced solid tumors with immune monotherapy or combined with first-line treatment, and most of the data comes from the KEYNOTE study Series
.

At the 2020 ASCO conference, K-drug single-agent first-line treatment of advanced malignant melanoma with a median follow-up of 66.
8 months showed that the 5-year OS rate was 43%4; at the 2020 ESMO conference, K-drug single-drug first-line treatment of PD- The median follow-up of KEYNOTE-024 for advanced non-small cell lung cancer with high L1 expression (PD-L1≥50%) was 59.
9 months, and the 5-year OS rate was 31.
9% 5
.

The application for the first-line treatment of MSI-H/dMMR mCRC indication for K-drug monotherapy was officially accepted by the National Medical Products Administration (NMPA) on November 12, 2020, and it is expected to be approved in the near future! Once the indication is approved, Drug K will become the first domestic PD-1 immune checkpoint inhibitor to guide clinical practice based on the MSI-H/dMMR status, which is a milestone in domestic precision immunotherapy
.

It is hoped that the approval of this indication will not only bring “de-chemotherapy” and high-quality long-term survival for Chinese patients with MSI-H/dMMR metastatic colorectal cancer, it will also promote precision tumor immunotherapy in the domestic clinical practice.
Floors
.