Pembrolizumab helps patients with multiple types of advanced tumors achieve long-term survival

At the 2022 European Medical Oncology (ESMO) Congress that concluded on September 13, the five-year survival follow-up data of multiple immunotherapy combined with chemotherapy for the first-line treatment of advanced non-small cell lung cancer (NSCLC) were released, including Merck's PD-1 inhibitor pembrolizumab (commonly known as "K drug") combined with chemotherapy.
5-year survival data
from two phase III clinical trials (KEYNOTE-189 and KEYNOTE-407) for the first-line treatment of metastatic non-small cell lung cancer.

Analysis of long-term follow-up data from two studies showed that pembrolizumab combined with platinum-based chemotherapy regimens confined better long-term survival than platinum-based chemotherapy, with five-year OS rates of 18.
4 percent and 19.
4 percent for first-line treatment of advanced squamous NSCLC or non-squamous NSCLC, respectively, compared with 11.
3 percent and 9.
7 percent for chemotherapy [^{1], [2].}

From 2012 to 2015, the overall five-year survival rate of lung cancer in China was 19.
7%^[3], of which the five-year survival rate of early-stage (stage I) lung cancer was 55.
47%, and once metastasized to stage IV lung cancer, the five-year survival rate dropped to 5.
27%[^4].

Most lung cancer patients in China have progressed to stage III and IV at the time of initial diagnosis ^[5].

Non-small cell lung cancer accounts for 85%
of lung cancer cases.

Based on the results of KEYNOTE-189 and KEYNOTE-407, the China Medical Products Administration approved pembrolizumab combined with chemotherapy in 2019 for the first-line treatment of metastatic squamous and non-squamous non-small cell lung cancer, which has become the preferred standard treatment for
patients with advanced lung cancer.

The long-term survival data of KEYNOTE-189 and KEYNOTE-407 patients released by ESMO have brought confidence and far-reaching significance
to improve the treatment level of advanced lung cancer patients in China, prolong the survival of patients, and thus improve the overall 5-year survival rate of lung cancer in China.

Pembrolizumab plus chemotherapy first-line therapy is the only PD-1 combination chemotherapy regimen
that has been shown to improve the five-year survival rate of metastatic non-small cell lung cancer.
IN ADDITION TO KEYNOTE-189 AND KEYNOTE-407, A PHASE III CLINICAL STUDY OF PEMBROLIZUMAB MONOTHERAPY IN SELECT POPULATIONS WITH METASTATIC NON-SMALL CELL LUNG CANCER HAS PREVIOUSLY PUBLISHED FIVE-YEAR SURVIVAL DATA, INCLUDING

● Phase III KEYNOTE-024 study to evaluate the five-year survival data of 31.
9% of patients with metastatic non-small cell lung cancer with pembrolizumab combined with chemotherapy with high PD-L1 expression (tumor proportion score TPS≥50%) ^[6];

● Phase III KEYNOTE-042 study evaluating pembrolizumab monotherapy for first-line treatment of PD-L1-positive PD-L1 expression (tumor proportion score TPS≥1%) in patients with metastatic non-small cell lung cancer for five years of longevity ^[7]
.
Based on the results of KEYNOTE-042, the first-line treatment of PD-L1 TPS with K drug was approved
in 2019 for ≥% metastatic NSCLC indication.

In China, in addition to the three indications for the treatment of advanced NSCLC, pembrolizumab has also been approved for five therapeutic indications, including

● First-line combination chemotherapy for unresectable locally advanced or metastatic esophageal cancer (including esophageal squamous cell carcinoma, esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma);

● Single-agent first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma of PD-L1 CPS≥20;

● Single-agent first-line treatment of patients with unresectable or metastatic high microsatellite instability (MSI-H) or mismatch repair genologically deficient type (dMMR) colorectal cancer (CRC);

● Single-agent second-line treatment of advanced esophageal cancer that has progressed after chemotherapy;

● Single-agent second-line treatment of unresectable melanoma
.

● Research data show that these treatment regimens based on pembrolizumab can also lead to long-term survival for patients with these malignancies:

● The two-year survival rate of patients with PD-L1 CPS≥10 esophageal cancer in combination chemotherapy is 30%[^8];

● The 5-year survival rate of 20 patients with head and neck squamous cell carcinoma ≥ treated with PD-L1 CPS as a single-agent first-line treatment was 19.
9 percent^[9];

● The two-year overall survival rate of patients with single-agent first-line MSI-H or dMMR whose KRAS, NRAS, and BRAF genes are all wild-type is ^{79 percent [10]};

● The five-year overall survival rate for single-agent second-line treatment of melanoma is 30.
1 percent ^[11].

Healthy China 2030 proposes to improve the overall five-year survival rate of tumors by 15 percentage points
.
The improvement of the five-year survival rate of advanced lung cancer, including the five-year survival rate of various malignant tumors, is obviously a help to
achieve this goal.
It is expected that the clinical research of pembrolizumab in the treatment of various malignant tumors will have more and longer survival data, and continue to strive for the goal of "longer, wider and higher", bringing more hope
to Chinese cancer patients.

       [1] M.
C.
Garassino et al.
, KEYNOTE-189 5-year update: First-line pembrolizumab (pembro) + pemetrexed (pem) and platinum vs placebo (pbo) + pem and platinum for metastatic nonsquamous NSCLC, 2022 ESMO, Abs #973MO

       [2] S.
Novello et al.
, 5-year updat from KEYNOTE-407: Pembrolizumab plus chemotherapy in squamous non-small cell lung cancer (NSCLC)， 2022 ESMO，Abs # 974MO

[3] Zeng HM，ChenWQ，Zheng RS，et al.
Changing cancer survival in China during 2003-15：a pooled analysis of 17 population-based cancer registries[J].
Lancet Glob Health，2018，6(5):e555-e567.
DOI:10.
1016/S2214-109X(18)30127-X.

ZHANG Minlu, WU Chunxiao, GONG Yangming, et al.
, Survival rate of lung cancer in Shanghai population[J].
China Oncology,2017,27(5):326 -333.
DOI:10.
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2017.
05.
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       [5] Shi JF，Wang L，Wu N，et al.
Clinical characteristics and medical service utilization of lung cancer in China,2005-2014:overall design and results from a multicenter retrospective epidemiologic survey[J].
Lung Cancer, 2019, 128:91-100.
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2018.
11.
031.

[6] Martin Reck et al.
, Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50 J Clin Oncol.
2021 Jul 20; 39(21):2339-2349.
doi: 10.
1200/JCO.
21.
00174.
Epub 2021 Apr 19.

       [7] Results 1274 patients were randomized to pembrolizumab or chemotherapy (n = 637 each).
Median (range) time from randomization to data cutoff (Apr 28, 2021) was 61.
1 (50.
0–76.
3) months.

       [8] Metges JP et al.
, FIrst-line Pembrolizumab Plus Chemotherapy Versus Chemotherapy in Advanced Esophageal Cancer: Longer-term Efficacy, Safety, and Quality-of-life Results From the Phase 3 KEYNOTE-590 Study, 2022 ASCO-GI, Oral Presentation

       [9] M.
Tahara et al.
, Pembrolizumab with or without chemotherapy for first-line treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): 5-year results from KEYNOTE-048 2022 ESMO, Abs #659MO

[10] Pembrolizumab injection instructions, 2021

[11] Caroline Robert et al.
, Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 studyLancet Oncol.
2019 Sep; 20(9):1239-1251.
doi: 10.
1016/S1470-2045(19)30388-2.
Epub 2019 Jul 22.