Academician Martin: The progress of gynecological oncology research in 2021 is encouraging, but the disappointments still need to be explored

In 2021, significant progress will be made in the treatment of ovarian, cervical, endometrial and trophoblastic cancers
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"NEJM Medical Frontier" invited Academician Martin of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology to sort out the above important progress
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"NEJM Frontiers in Medicine" is jointly developed by Jiahui Medical Research and Education Group (J-Med) and the New England Journal of Medicine (NEJM)
.

As in the past three years, we will launch a review of clinical research in various important disease areas one after another, so stay tuned
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 The Department of Obstetrics and Gynecology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, opened the official homepage of the New England Journal of Medicine (NEJM) and reviewed the articles published in the journal in the past year, although many research articles related to the global Covid-19 Despite the latest development of the epidemic, gynecological oncologists at home and abroad are still sticking to their jobs, constantly thinking about and answering important diagnosis and treatment questions in this professional field, in order to bring the best treatment strategies to patients
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 In 2021, we will see Chinese experts participating more and even leading international multicenter randomized controlled studies
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Professor Zang Rongyu from Zhongshan Hospital Affiliated to Fudan University participated in the DESKTOP Ⅲ study to answer the question of whether secondary cytoreduction surgery for ovarian cancer is effective; the results of the NORA study led by Professor Wu Xiaohua from Fudan University Cancer Hospital were published in Ann Oncol; the author and Chinese gynecological oncology colleagues jointly The completed Asian multi-center study L-MOCA also won a seat at the 2021 American Clinical Oncology (ASCO) Annual Meeting and will be published soon, reaffirming that Chinese and even Asian patients with ovarian cancer can benefit from PARP inhibitors; led by Professor Xiang Yang from Peking Union Medical College Hospital The results of the CAP 01 study, published in Lancet Oncol, provide a new option for salvage therapy in patients with high-risk trophoblastic tumors that recur after chemotherapy
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 We are also seeing more new drugs being sought in the field of gynecological oncology
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The failure of IMagyn050 and NINJA in the field of ovarian cancer, and the success of the KEYNOTE trial in cervical cancer and endometrial cancer, raise new questions for us: what kind of gynecological tumor is suitable for the extremely hot immunotherapy in other tumor types Patients; to follow or to innovate also deserves more consideration
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mirvetuximab soravtansine (MIRV), as the first antibody-conjugated drug to announce the results of phase 3 clinical trials in the field of ovarian cancer, although the results did not meet expectations, what valuable thinking can it bring to the research and development of innovative drugs in my country? Below we present important studies in ovarian, cervical, endometrial, and trophoblastic tumors in 2021
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A surgical treatment of ovarian cancer NEJM published the results of the DESKTOP Ⅲ study in early December [1], the study confirmed that secondary cytoreduction surgery can significantly prolong overall survival (OS) for suitable patients
.

The study enrolled 407 patients with a positive Gynecologic Oncology Task Force (AGO) score, and randomly assigned 206 patients to receive cytoreductive surgery plus chemotherapy, and 201 patients to receive chemotherapy only
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A positive AGO score is defined as a performance status score of 0 by the Eastern Cooperative Oncology Group, ascites less than 500 ml, and complete resection of the initial tumor debulking surgery (see "China-Korea-European Collaborative Study Tops NEJM, Confirming the Value of Surgery for Recurrent Ovarian Cancer")
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The results of the study showed that 75.
5% of the patients in the surgery group achieved complete resection
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The median OS was 53.
7 months in the surgery group and 46.
0 months in the non-surgery group (HR, 0.
75; P=0.
02)
.

Patients who underwent complete resection had the best prognosis, with a median OS of 61.
9 months
.

In subgroup analyses of each prognostic factor, there was benefit in the surgery group
.

There were no significant differences in quality of life scores between the two groups during the 1-year follow-up period, and no perioperative mortality was observed within 30 days after surgery
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Thus, in patients with recurrent ovarian cancer, for appropriate patients, chemotherapy after secondary debulking resulted in a longer OS than chemotherapy alone
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 Drug therapy In recent years, PARP inhibitors have led the clinical research in the field of ovarian cancer.
Several key studies of PARP inhibitors have also been published at major conferences.
New stratified analysis, post-hoc analysis subgroup results or long-term follow-up results, such as SOLO series and ARIEL series will not be repeated here
.

 It is worth mentioning that Professor Wu Xiaohua's NORA research [2]
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From September 2017 to February 2019, Professor Wu Xiaohua led 30 domestic centers to enroll 265 patients, and confirmed that under individualized starting dose, compared with placebo, niraparib significantly prolonged platinum-sensitive recurrent ovarian cancer Patients had median progression-free survival (mPFS, 18.
3 vs.
5.
4 months; HR, 0.
32; P<0.
0001), with benefit regardless of BRCA mutation
.

 The L-MOCA study led by Academician Martin of the Chinese Academy of Engineering and participated by Malaysia also confirmed the efficacy and safety of olaparib as a single drug in Asian platinum-sensitive recurrent ovarian cancer [3], and the mPFS was 16.
1 months.
, also demonstrated that patients with platinum-sensitive recurrent ovarian cancer benefited from oral olaparib maintenance therapy regardless of BRCA mutation
.

Of course, different patient populations were used in different studies and methods of assessing PFS were different, so non-head-to-head studies cannot be used for direct comparison
.

But we can see that the development of new drugs brings new hope to ovarian cancer patients
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 The 2021 European Society for Medical Oncology (ESMO) annual meeting also announced the results of the OreO study [4], which answered the question of whether PARP inhibitor maintenance therapy can be received again after PARP inhibitor maintenance therapy
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This is a randomized, placebo-controlled phase 3b study of 220 patients with non-mucinous epithelial ovarian cancer who have received at least 1 line of maintenance therapy with a PARP inhibitor and who have responded to their most recent platinum-containing chemotherapy, receiving olapa maintenance therapy until disease progression
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The primary endpoint of the study was investigator-assessed PFS
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 The results showed that patients with or without BRCA mutation benefited significantly from re-maintenance therapy with olaparib
.

The mPFS of the BRCA mutation cohort and the control group was 4.
3 months and 2.
8 months, respectively (HR, 0.
57; P=0.
022), while the mPFS of the BRCA mutation-free cohort and the control group was 5.
3 months and 2.
8 months, respectively (HR, 0.
43; P=0.
0023)
.

This study answers the clinical question of whether patients can be treated with PARP inhibitors again.
Of course, the prognosis of these patients is poor, and more clinical new drugs need to be developed to meet the treatment needs of these patients
.

 So, what is the result of immunotherapy, which is in full swing in the field of oncology this year, in the field of ovarian cancer? In June and November 2021, J Clin Oncol published the results of the IMagyn050 and NINJA studies, respectively
.

 IMagyn050 is a randomized, placebo-controlled, phase 3 trial of atezolizumab, bevacizumab combined with chemotherapy in the treatment of newly diagnosed stage III or IV ovarian cancer [5]
.

A total of 301 International Federation of Gynecology and Obstetrics (FIGO) stage III-IV ovarian cancer patients with macroscopic residual lesions after initial cytoreduction or planned to receive neoadjuvant chemotherapy and intermittent cytoreduction were enrolled.
According to FIGO staging, Eastern Cooperative Oncology Group performance status score, tumor immune cell PD-L1 staining, and treatment strategy were stratified
.

The enrolled patients were randomly divided into atezolizumab (1200 mg) group every three weeks or placebo control group (1-22 cycles), combined with paclitaxel + carboplatin chemotherapy (1-6 cycles) + Valimumab (15 mg/kg, 2-22 cycles)
.

mPFS was 19.
5 and 18.
4 months in intent-to-treat patients (ITT) in the atezolizumab and placebo groups, respectively (HR, 0.
92; P=0.
28), and 20.
8 in PD-L1-positive patients, respectively month and 18.
5 months (HR, 0.
80; P=0.
038)
.

Interim (immature) OS results showed no difference between groups
.

This evidence does not support the use of immune checkpoint inhibitors for the initial treatment of newly diagnosed ovarian cancer
.

 NINJA is a multicenter, open-label, randomized, phase 3 clinical trial conducted in Japan [6] to evaluate the efficacy and safety of nivolumab versus chemotherapy in patients with platinum-resistant ovarian cancer
.

The trial enrolled 316 patients with platinum-resistant epithelial ovarian cancer who received ≤1 line of chemotherapy after a diagnosis of platinum-resistant disease
.

Patients were randomized 1:1 to nivolumab (240 mg every 2 weeks, n=157) or chemotherapy (gemcitabine or liposomal doxorubicin, n=159)
.

The median OS for the primary endpoint of the study was 10.
1 months and 12.
1 months, respectively (HR, 1.
0; P=0.
808)
.

The secondary endpoint mPFS was 2.
0 and 3.
8 months (HR, 1.
5; P=0.
002), and the overall response rate was not statistically different between groups (7.
6% vs.
13.
2%; P=0.
191)
.

The nivolumab group had longer duration of response (18.
7 vs.
7.
4 months), fewer treatment-related adverse events (61.
5% vs.
98.
1%), and no new safety signals
.

Thus, in platinum-resistant ovarian cancer, although well tolerated, nivolumab did not improve OS and had worse PFS than chemotherapy
.

 In both the KEYNOTE-100 and JAVELIN studies of pembrolizumab and avelumab in recurrent ovarian cancer, objective response rates were in the single digits
.

This exciting result is driven by an objective response rate of 15% in a small phase 2 study of nivolumab in patients with platinum-resistant ovarian cancer, with 2 additional patients showing sustained complete responses The NINJA study, however, backfired, and the program ultimately failed
.

So far, multiple studies of immune checkpoint inhibitors in recurrent epithelial ovarian cancer have brought disappointing results, and no immune checkpoint inhibitor has so far been approved for the treatment of epithelial ovarian cancer
.

 These data may suggest that ovarian cancer and other solid tumors have different biological characteristics, and new combination therapy strategies need to be devised in order to provide a successful solution to this deadly disease
.

Whether the luxurious regimen of PARP inhibitor + anti-vascular + immunotherapy + chemotherapy can bring benefits to patients, we will wait and see the ongoing DUO-O study (NCT03737643)
.

 In addition to the failure of clinical studies of ovarian cancer immunotherapy, antibody-drug conjugates have not brought good news
.

MIRV is a novel antibody-drug conjugate that targets tumor cells by conjugating a folate receptor alpha antibody, a cleavable linker, and maytansinoid DM4 (tubulin inhibitor)
.

FORWARD I is a randomized phase 3 clinical trial of MIRV versus chemotherapy in patients with platinum-resistant ovarian cancer [7]
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The trial's primary endpoint, PFS, was not statistically different between the intention-to-treat population and the population with high folate receptor alpha expression
.

Advantages were observed in the MIRV arm in all secondary endpoints, including objective response rate (24% vs.
10%) and CA125 response (53% vs.
25%) in the high folate receptor alpha expressing population
.

There were fewer treatment-related adverse events of grade 3 or higher in the MIVA arm than chemotherapy, and fewer adverse events leading to dose reduction or discontinuation
.

This result supports continued research on the efficacy of MIRV in patients with high expression of folate receptor alpha
.

In the field of locally advanced cervical cancer, the 2021 ASCO annual meeting announced a phase 3 randomized trial called OUTBACK in Australia [8] to study the effect of adding adjuvant chemotherapy after concurrent chemoradiotherapy
.

A total of 919 patients with locally advanced cervical cancer (FIGO 2008 stage IB1 and lymph node positive, IB2, II, III or IVA) who were eligible for initial radical concurrent chemoradiotherapy were included in the trial and were randomly assigned to the standard cisplatin-containing regimen concurrent chemoradiotherapy group.
(control group, n=456) or standard cisplatin-containing regimen concurrent chemoradiotherapy followed by 4 cycles of adjuvant chemotherapy (ACT group, adjuvant chemotherapy was carboplatin combined with paclitaxel, n=463)
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Both the primary end point (5-year survival) and the secondary end point (PFS) suggested no additional benefit from the addition of adjuvant chemotherapy
.

 The results of a randomized controlled phase 3 clinical trial (KEYNOTE-826) of pembrolizumab in persistent, recurrent or metastatic cervical cancer were published in NEJM [9]
.

Among 548 patients with PD-L1 combined positive score (CPS) ≥1, mPFS was 10.
4 months in the pembrolizumab group and 8.
2 months in the placebo group (HR, 0.
62; P<0.
001)
.

In the intention-to-treat population of 617, mPFS was 10.
4 months in the pembrolizumab group and 8.
2 months in the placebo group (HR, 0.
65; P<0.
001)
.

Among the 317 patients with PD-L1 combined positive score ≥10, the mPFS of the two groups was 10.
4 months and 8.
1 months, respectively (HR, 0.
58; P<0.
001)
.

The 24-month overall survival rates in the pembrolizumab group and placebo group were 53.
0% and 41.
7% (HR, 0.
64; P<0.
001), 50.
4% and 40.
4% (HR, 0.
67), respectively, in the three dimensions described above; P<0.
001), and 54.
4% and 44.
6% (HR, 0.
61; P=0.
001)
.

This study demonstrates that in patients with persistent, recurrent or metastatic cervical cancer receiving chemotherapy (with or without bevacizumab), pembrolizumab treatment resulted in a significant benefit in PFS and OS ( See "NEJM-ESMO2021: Pembrolizumab combined with chemotherapy significantly improves the prognosis of advanced cervical cancer | Kong Beihua Review")
.

At this year's International Gynecologic Oncology Society (IGCS) annual meeting, researchers orally reported the results of the EMPOWER-Cervical 1 study [10]
.

This is a comparison of cemiplimab (a PD-1 inhibitor) versus investigator's choice of chemotherapy (pemetrexed, topotecan, or irinotecan, gemcitabine, or vinorelbine only) in patients who have progressed after first-line platinum-based chemotherapy An open-label, 1:1 randomized, multicenter phase 3 clinical trial in recurrent/metastatic cervical cancer with a total of 608 patients
.

The results showed a significant benefit in the primary endpoint of median OS, which was 12.
0 months vs.
8.
5 months in the two groups (HR, 0.
69; P=0.
00011), and the secondary endpoint of mPFS in the two groups was 2.
8 months vs.
2.
9 months, respectively month
.

3.
Endometrial Cancer Regarding the diagnosis and treatment of endometrial cancer, clinical research in recent years has mainly focused on its molecular typing and immunosuppressive therapy (click to view "NEJM Medical Frontiers: 2020 Inventory of Important Gynecological Cancer Clinical Research" written by Prof.
Wu Lingying)
.

An important update from 2020 is the announcement of the results of the Phase 3 clinical trial KEYNOTE-775
.

 The results of this randomized controlled phase 3 clinical trial were announced at the 2021 Society of Gynecologic Oncology (SGO) annual meeting [11]
.

The study included patients with advanced endometrial cancer who had previously received 1 line of platinum-based chemotherapy and up to 2 lines of platinum-based chemotherapy if they had received adjuvant/neoadjuvant therapy
.

A total of 827 patients (DNA mismatch repair normal [pMMR], n = 697; DNA mismatch repair deficient [dMMR], n = 130) were enrolled and received lenvatinib + pembrolizumab (n = 411) ) or physician-chosen treatment (n=416)
.

 After a median follow-up of approximately 1 year, significant prolongation of its primary endpoints, PFS and OS, was observed in both pMMR patients and overall patients
.

Based on the results of this study, the European Medicines Agency approved the combination regimen for the treatment of patients with advanced or recurrent endometrial cancer that has progressed after platinum-based chemotherapy
.

While the United States has previously approved pembrolizumab and dostarlimab as single agents for the treatment of patients with MSI-H or dMMR endometrial cancer, this time, based on the results of the KEYNOTE-775 study, this combination therapy is approved for non-MSI-H or dMMR of endometrial cancer patients
.

The different indications in Europe and the United States raise a new question for us: Is PD-1 alone or combined with TKIs better for patients with MSI-H or dMMR? This question deserves to be answered in more clinical studies
.

 The 2021 IGCS annual meeting also announced the results of a multicenter, randomized controlled trial in Italy on patient follow-up [12]
.

The study, called TOTEM, enrolled 1,866 Italian patients to try to answer whether patients with high- or low-risk endometrial cancer require intensive follow-up
.

The final results show that no matter whether it is a high-risk or low-risk patient, it is sufficient to maintain the minimum required follow-up.
Increasing the frequency of follow-up and examination does not improve the patient's OS, PFS or quality of life, but increases the medical burden
.

Minimum follow-up requirements are as follows: for high-risk (IA, G3, or IB) patients, follow-up every 4 months for the first 2 years, every 6 months for the next 3 years, and annual cervical smear and chest, abdomen, and pelvic CT for the first two years ; For low-risk (IA, G1~2) patients, follow-up every six months is sufficient
.

This study has some implications for patient management with limited medical resources or during the Covid-19 epidemic, which can be used for clinical reference
.

Four trophoblastic carcinoma trophoblastic tumors are relatively rare, so there are few clinical studies on this disease in the past, and its treatment is still mainly surgery and chemotherapy
.

The results of the CAP 01 trial on trophoblastic tumor led by Professor Xiang Yang of Peking Union Medical College Hospital were published in Lancet Oncol in October 2021 [13]
.

This single-center, open-label, phase 2 trial enrolled 20 patients with high-risk (FIGO score ≥7) chemotherapy-resistant or recurrent trophoblastic tumors who received at least ≥2 lines of unsuccessful combination chemotherapy, Eastern Cooperative Oncology Group The performance status is scored from 0 to 2 points
.

Patients received camrelizumab (200 mg) intravenously every 2 weeks in combination with oral apatinib (250 mg once daily) until disease progression or intolerable toxicity
.

The primary endpoint of the study was objective response rate as assessed by serum human chorionic gonadotropin concentrations
.

The results showed that the objective response rate was 55%, and 10 patients (50%) achieved complete response
.

The results of this study provide good evidence for the use of PD-1 inhibitors combined with VEGFR inhibitors in high-risk chemotherapy-resistant or recurrent trophoblastic tumors
.

 Let us review the results of the TROPHIMMUN trial (a phase 2 clinical trial of avelumab monotherapy) presented at the 2020 ASCO Annual Meeting [14]
.

A total of 15 patients with single-agent chemotherapy-resistant trophoblastic tumors were included in the trial, 80% of whom had a FIGO score of <7, and the treatment regimen was intravenous avelumab 10 mg/kg every 2 weeks until human chorionic stimulation Gonadal hormones reached normal levels, followed by 3 courses of consolidation therapy
.

The primary endpoint of normalization of human chorionic gonadotropin was 53.
3%
.

 The treatment populations of the two studies were different, one was resistant to single-agent chemotherapy and the other was resistant to multi-drug chemotherapy; the FIGO risk score was also different (CAP 01 enrolled high-risk patients with FIGO score ≥ 7, while TROPHIMMUN enrolled FIGO Low-risk patients with a score of <7 points); the treatment regimens are also different, the low-risk group adopts the immune single drug, and the high-risk group adopts the combination of immune + TKI
.

However, the two studies achieved similar curative effects.
About 50% of the patients' human chorionic gonadotropin returned to normal levels, which suggested a new treatment idea and treatment option for the salvage treatment of trophoblastic tumors
.

Of course, limited by the small number of patients and all single-arm studies, we still need a larger sample study to further confirm the efficacy and safety
.

Five Outlook In addition to the published clinical research results, we also see that many new investigational drugs are being tested in clinical trials of gynecological oncology.
The method can bring longer survival and better quality of life for gynecological cancer patients
.

Experts introduce Martin, academician of the Chinese Academy of Engineering, director of the Department of Obstetrics and Gynecology, Tongji Medical College, Huazhong University of Science and Technology
.

Former chairman of the Chinese Medical Association Gynecological Oncology Branch; currently director of the National Key Discipline of Obstetrics and Gynecology, and director of the National Clinical Research Center for Obstetrics and Gynecology
.

His research interests include gynecological tumors and molecular biology of tumor metastasis
.

Good at diagnosis and treatment of gynecological tumors and gynecological diseases, proficient in gynecological surgery, endoscopic and robotic surgery
.

He is the editor-in-chief of the guideline for the diagnosis and treatment of gynecological malignant tumors in China, and the Chinese and English version of Obstetrics and Gynecology, a textbook for the national eight-year plan for medical students
.

He has published 486 papers as the first or corresponding author, among which more than 163 papers have been published in SCI journals represented by Nature Genetics, J Clin Invest, J Exp Med and J Nat Can Invest
.

He has won the Wu Jieping-Paul Janssen Award, the Ho Leung Ho Lee Foundation Science and Technology Award, the first prize of the Natural Science Award of the Ministry of Education, the second prize of the National Science and Technology Progress Award and many other awards
.

Reference 1.
Harter P, Sehouli J, Vergote I, et al.
Randomized trial of cytoreductive surgery for relapsed ovarian cancer.
N Engl J Med 2021;385:2123-31.
2.
Wu XH, Zhu JQ, Yin RT, et al.
Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, controlled phase III trial.
Ann Oncol 2021;32:512-21.
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Gao QL, Zhu JQ, Zhao WD, et al.
L-MOCA: An open-label study of olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer.
J Clin Oncol 2021;39:15_suppl, e17526-e17526.
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Pujade-Lauraine E.
Maintenance olaparib rechallenge in patients (pts) with ovarian carcinoma (OC) previously treated with a PARP inhibitor (PARPi): Phase IIIb OReO/ENGOT Ov-38 trial.
ESMO Congress 2021, Abstract LBA33.
5.
Moore KN, Bookman M, Sehouli J, et al.
Atezolizumab, bevacizumab, and randomized chemotherapy for newly diagnosed stage III or IV ovarian cancer: a placebo-controlled phase III trial (IMagen050/GOG ​​3015/ENGOT-OV39).
J Clin Oncol 2021;39:1842-55.
6.
Hamanishi J, Takeshima N, Katsumata N, et al.
Nivolumab versus gemcitabine or pegylated liposomal doxorubicin for patients with platinum-resistant ovarian cancer: Open-label, randomized trial in Japan (NINJA).
J Clin Oncol 2021;39:3671-81.
7.
Moore KN, Oza AM, Colombo N, et al.
Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I.
Ann Oncol 2021;32:757-65.
8.
Mileshkin LR, Moore KN, Barnes E, et al.
Adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone:The randomized phase III OUTBACK Trial (ANZGOG 0902, RTOG 1174, NRG 0274).
J Clin Oncol 2021;39:18_suppl, LBA3-LBA3.
9.
Colombo N, Dubot C, Lorusso D, et al.
Pembrolizumab for persistent, recurrent, or metastatic cervical cancer.
N Engl J Med 2021;385:1856-67.
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Tewari K, Monk B, Vergote B, et al.
EMPOWER-CERVICAL 1/GOG-3016/ENGOT-CX9: Results of phase 3 trial of cemiplimab vs investigator's choice chemotherapy in recurrent/metastatic cervical carcinoma.
IGCS 2021.
Abstr 331.
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Makker V.
A multicenter, open-label, randomized, phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer.
SGO 2021.
Abstr 11512.
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Zola P, Ciccone G, Angioli R, et al.
Does intensive follow-up improve overall survival in endometrial cancer patients? Results from the TOEM randomized controlled trial.
IGCS 2021.
Abstr 393.
13.
Cheng H, Zong L, Kong Y, et al.
Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial.
Lancet Oncol 2021;22:1609-17.
14.
Benoit Y, Bolze PA, Lotz JP, et al.
Avelumab in patients with gestational trophoblastic tumors resistant to monochemotherapy: Final outcomes of TROPHIMMUN phase II trial, cohort A.
J Clin Oncol 2020;38:18_suppl, LBA6008-LBA6008.
Copyright information This article is sponsored by Jiahui Medical Research and Education Group (J-Med) and "New The English Journal of Medicine (NEJM) co-created the "NEJM Frontiers in Medicine" translation, editing or commissioningCamrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial.
Lancet Oncol 2021;22:1609-17.
14.
Benoit Y, Bolze PA, Lotz JP, et al.
Avelumab in patients with gestational trophoblastic tumors resistant to monochemotherapy: Final outcomes of TROPHIMMUN phase II trial, cohort A.
J Clin Oncol 2020;38:18_suppl, LBA6008-LBA6008.
Copyright information This article is by Jiahui Medical Research and Education Translated, edited or commissioned the "NEJM Frontiers in Medicine" jointly created by the Group (J-Med) and the New England Journal of Medicine (NEJM)Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial.
Lancet Oncol 2021;22:1609-17.
14.
Benoit Y, Bolze PA, Lotz JP, et al.
Avelumab in patients with gestational trophoblastic tumors resistant to monochemotherapy: Final outcomes of TROPHIMMUN phase II trial, cohort A.
J Clin Oncol 2020;38:18_suppl, LBA6008-LBA6008.
Copyright information This article is by Jiahui Medical Research and Education Translated, edited or commissioned the "NEJM Frontiers in Medicine" jointly created by the Group (J-Med) and the New England Journal of Medicine (NEJM)LBA6008-LBA6008.
Copyright information This article was translated, written or commissioned by "NEJM Frontiers of Medicine" jointly created by Jiahui Medical Research and Education Group (J-Med) and "New England Journal of Medicine" (NEJM)LBA6008-LBA6008.
Copyright information This article was translated, written or commissioned by "NEJM Frontiers of Medicine" jointly created by Jiahui Medical Research and Education Group (J-Med) and "New England Journal of Medicine" (NEJM)
.

The full text of the Chinese translation and the included figures are exclusively authorized by the NEJM Group
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