A Review of the Anticancer Drugs Approved in China in 2019

Numerous anticancer drugs were marketed in China in 2019. Let’s today review the 7 blockbuster innovative oncology drugs approved by the NMPA (National Medical Products Administration of China) in 2019, which have greatly improved the treatment dilemma of oncology patients in China.

The first biosimilar in China: Rituximab Injection

The NMPA approved the marketing registration application of the Rituximab Injection (trade name: Hanlikang) developed by Shanghai Henlius Biotech, Inc. on Feb. 22, 2019. As the first biosimilar approved in China, the drug is mainly used to treat non-Hodgkin lymphoma. The approval of Hanlikang was based on a multicenter (33 centers), randomized, double-blind phase III clinical study that enrolled 407 untreated CD20-positive DLBCL subjects who were separately treated with the regimen of Hanlikang in combination with CHOP (H-CHOP) and regimen of Rituxan in combination with CHOP (R-CHOP), with the primary endpoint being the optimal overall response rate (ORR) within 6 cycles.

The results showed that the therapeutic equivalence between the Hanlikang group and Rituxan group was established (92.5% vs 92.1%), and the two groups had no statistical difference (P>0.05) in terms of the safety data. The results of this phase III clinical study mean that Hanlikang’s efficacy and safety are similar to those of Rituxan. Hanlikang has also been approved by the Chinese Pharmacopoeia Commission to use the generic name of Rituximab Injection.

Second-generation EGFR-TKI: dacomitinib

There was big news on May 15, 2019 that the new oncology drug dacomitinib (trade name: Vizimpro) was approved for marketing in China! Developed by the well-known pharmaceutical enterprise Pfizer, dacomitinib belongs to second-generation EGFR-TKIs, with the indication approved being "monotherapy for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-activating mutations (exon 19 deletion or exon 21 L858R substitution mutations)". The approval of the drug was based on an international, multicenter, randomized, open-label, phase III clinical study (ARCHER1050) that assessed the efficacy and safety of dacomitinib (second-generation EGFR-TKI) or gefitinib (first-generation EGFR-TKI).

The competition of the EGFR-targeted drugs for lung cancer is fierce, with many marketed, including the first-generation (gefitinib, etc.), second-generation (afatinib) and third-generation (osimertinib) drugs.

Even in this case, though, the marketing of dacomitinib in China still attracted great attention because 1: its median progression-free survival in the clinical trial of the Chinese patients with EGFR mutations reached 18.4 months far more than that of the first-generation drug; 2: it is currently the only targeted drug proved to have significantly prolonged the overall survival of patients with EGFR mutations compared to the standard therapy. The drug has now been approved in the U.S., the EU, Japan, and Canada, etc. as a first-line treatment.

China’s first and only drug for the giant cell tumor of bone: denosumab

Denosumab (trade name: Xgeva) was approved by the NMPA on May 21, 2019 to treat adults and skeletally mature adolescents (defined as having at least one mature long bone and weighing >45 kg) with giant cell tumor of bone (GCTB) that is unresectable or where surgical resection is likely to result in severe morbidity. It is China’s first and only drug for the GCTB.

The analysis of the Study 20040215 announced at the 2017 European Society for Medical Oncology (ESMO) annual meeting showed that the overall response rate of patients with resectable GCTB after neoadjuvant denosumab treatment was 80%; 44% of patients who had surgery underwent a less morbid procedure; and 37% of patients required no surgery. Denosumab brings effective long-term disease control benefits to patients with unresectable GCTB with a 5-year progression-free survival (PFS) rate of 88%.

Denosumab has freed patients from the pain of repeated surgery, controlled the disease progression and effectively improved the prognosis and life quality. And orthopedic oncology doctors finally have a choice other than surgery for unresectable GCTB, which is gratifying.

China’s first anti-CD38 monoclonal antibody drug: daratumumab

The NMPA approved the imported drug registration application of Xian Janssen’s Daratumumab Injection on July 5, 2019 for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.

According to the results of both GEN501 and SIRIUS studies, monotherapy daratumumab had some hematologic response rate in RRMM patients after high care. In the GEN501 study, patients had received a median of 4 prior treatments, 64% had disease refractory to bortezomib and lenalidomide, and the overall hematologic response rate was 36%. In the SIRIUS study, patients had received a median of 5 prior treatments, up to 85% had disease refractory to bortezomib and lenalidomide, and the ORR was 29.2%. The conjoint analysis of the 2 studies showed that daratumumab monotherapy could enable nearly 1/3 of RRMM patients to reach hematologic response, with the median duration of response of 7.6 months and the median OS of 20.1 months.

New-generation highly selective androgen receptor antagonist: apalutamide

Apalutamide was approved by the NMPA on Sep. 6, 2019 to start a new stage of prostatic cancer treatment in China. Prostatic cancer is commonly triggered by excessive androgen (including testosterone), therefore, the conventional treatment is to reduce the androgen levels in patients, which can be achieved clinically through surgical castration and/or androgen deprivation therapy (ADT).

Castration-resistant prostate cancer (CRPC) is a form of advanced prostate cancer and can be divided into non-metastatic CRPC (NM-CRPC) and metastatic CRPC (mCRPC). With ADT, the disease will still progress and have a poor prognosis, therefore, the NM-CRPC stage is a stage very critical to prostate cancer patients. If this stage is defended to delay the occurrence of metastasis as far as possible, patients’ disease progression and mortality risk will be greatly reduced.
As a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial, SPARTAN enrolled 1,207 NM-CRPC patients randomized into apalutamide group (240mg/d, n=806) and placebo group (n=401).

The trial results showed a 72% reduction in the risk of distant metastasis or death and median metastasis-free survival (MFS) of 40.5 months for patients in the apalutamide group compared to 16.2 months for patients in the placebo group. The approval of apalutamide will not only improve the survival of advanced prostate cancer patients but also gradually develop and start to establish the NM-CRPC treatment concept clinically, being a milestone in the prostate cancer treatment in China.

The first PD-L1 inhibitor marketed in China: durvalumab

The NMPA approved the marketing application of AstraZeneca’s new anticancer drug—Durvalumab Injection (trade name in English: Imfinzi, trade name in Chinese: 英飞凡) on Dec. 12, 2019, which is used to treat the unresectable stage III NSCLC without progression after chemoradiotherapy. It has become the first PD-L1 inhibitor approved in Mainland China and met the market demand for the stage III NSCLC drug unmet previously and may start a new market competition pattern of PD-1/PD-L1 inhibitors.

The approval is based on the Pacific study. The results of the study showed that the median PFS of patients receiving durvalumab was prolonged by nearly one year (17.2 vs 5.6 months) compared with placebo. In terms of survival time, the 3-year OS rate of patients in Imfinizi group was 57%, while that of placebo group was only 43.5%, which means that more than half of patients in advanced stage survived 3 years successfully with Imfinizi. In addition, durvalumab also increased ORR (28.4% vs 16%) and prolonged the time of death or distant metastasis (28.3 vs 16.2 months).

A new choice for classical Hodgkin lymphoma: tislelizumab

China approved another cancer antibody drug: tislelizumab on Dec. 27, 2019 to treat patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL). The approval of tislelizumab’s cHL indication was supported by the pivotal clinical study called BGB-A317-203.

The study enrolled a total of 70 r/r cHL patients. All of those patients had received conventional treatments such as radiotherapy and chemotherapy, and some of them even received autologous stem-cell transplantation, however, their conditions were difficult to control or relapsed after previous treatments. Their objective response rate (ORR) reached 87% after receiving tislelizumab treatment, and 44 patients (62.9%) reached complete response (CR).

In similar clinical studies, the ORRs of other anti-PD-1 antibodies could also reach 70%~80% which was close to the ORR of tislelizumab, however, their CRs generally could reach only 20%~30%.

The CR achieved by tislelizumab is currently the best result of anti-PD-1/PD-L1 antibodies in treating r/r CHL.

The CR is particularly important for cHL patients, which means that the treatment is quite thorough. A previous 14-year follow-up visit to 188 Hodgkin lymphoma patients discovered that patients who could survive more than 10 years all had the CR after treatment.

2019 was a fruitful year. I look forward to the marketing of more new drugs in China in 2020 to benefit the Chinese people.

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