Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 18  |  Issue : 2  |  Page : 482-487

Camrelizumab (SHR-1210) with carboplatin and albumin-binding paclitaxel in patients with metastatic or recurrent cervical cancer: An open-label, phase 2 trial


1 Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China
2 Department of Gynecology, People's Hospital of Zouping City, Binzhou, Shandong, People's Republic of China

Date of Submission15-Oct-2021
Date of Decision16-Feb-2022
Date of Acceptance03-Mar-2022
Date of Web Publication20-May-2022

Correspondence Address:
Naifu Liu
Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong
People's Republic of China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.jcrt_1851_21

Rights and Permissions
 > Abstract 


Aims: This study evaluates the safety and preliminary antitumor efficacy of camrelizumab with albumin-binding paclitaxel and cisplatin as first-line therapy for patients with recurrent or metastatic cervical carcinoma.
Methods and Material: In this phase 2, open-label, prospective study, 35 patients with recurrent or metastatic cervical carcinoma with no previous systemic chemotherapy were included. The patients were treated with a maximum of six cycles of camrelizumab on day 1, albumin-binding paclitaxel, and carboplatin on day 2, every 3 weeks, followed by camrelizumab once every 3 weeks. The primary outcomes were objective response rate (ORR) and disease control rate (DCR). Secondary outcomes were duration of response (DoR) and safety. Furthermore, 27 patients were included in the per-protocol set for efficacy analysis, whereas for the safety analysis, all patients were included.
Results: The median follow-up was 4.53 months, and the complete response, partial response, and stable disease were also achieved in 4 (14.81%), 6 (22.22%), and 13 (48.15%) patients. The ORR and DCR were 40.00% (95% confidence interval: 21.13–61.33%) and 92.00% (73.97–99.01%), respectively. The median DoR was 6.70 months. In addition, the most common adverse events (AEs) were reactive cutaneous capillary endothelial proliferation (RCCEP) (23, 65.71%), gastrointestinal reaction (8, 22.86%), and fever (8, 22.86%). Grade 3 AEs included 5 (14.29%) myelosuppression, and grade 4 AEs included 1 (2.86%) RCCEP and 1 (2.86%) bladder inflammation.
Conclusions: Combination therapy of camrelizumab and albumin-bound paclitaxel and carboplatin shows promising efficacy and manageable toxicities in patients with recurrent or metastatic cervical cancer.

Keywords: Albumin-bound paclitaxel, camrelizumab (shr-1210), carboplatin, cervical cancer, prospective study


How to cite this article:
Zhang X, Chen J, Liu N, Wang Q, Wu Q, Gao F, Sang Y, Wang P. Camrelizumab (SHR-1210) with carboplatin and albumin-binding paclitaxel in patients with metastatic or recurrent cervical cancer: An open-label, phase 2 trial. J Can Res Ther 2022;18:482-7

How to cite this URL:
Zhang X, Chen J, Liu N, Wang Q, Wu Q, Gao F, Sang Y, Wang P. Camrelizumab (SHR-1210) with carboplatin and albumin-binding paclitaxel in patients with metastatic or recurrent cervical cancer: An open-label, phase 2 trial. J Can Res Ther [serial online] 2022 [cited 2022 Jul 7];18:482-7. Available from: https://www.cancerjournal.net/text.asp?2022/18/2/482/345533




 > Introduction Top


Cervical cancer is the fourth most commonly diagnosed and deadliest cancer in women globally.[1] In 2013, 485,000 women were diagnosed with cervical cancer globally, which resulted in 236,000 deaths.[2] Although preventable, it remains one of the major cancers that cause death in women, especially in developing countries. Interestingly, early-stage cervical cancer can be eradicated, and platinum-based chemotherapy combined with radiation was deemed highly active in the treatment of advanced cervical cancer during the late 1990s[3]; approximately three decades passed before the FDA approved a new, targeted therapy for cervical cancer, bevacizumab, to be used in addition to the traditional platinum chemotherapy doublet.[4] However, despite active research, the prognosis for recurrent, persistent, or metastatic disease is still poor.[5] Chemotherapy remains the treatment of choice for these patients; however, it poses a palliative character that is neither curative nor associated with long-term disease control.[6] Clinical trials on novel developed therapies are currently being studied to increase the options for management in this patient population.[7] Currently, data are limited but are increasing in the use of immune checkpoint inhibitors in cervical cancer.[8]

An essential feature of cervical carcinoma is its association with human papillomavirus infection, demonstrating an upregulation of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) in cervical cancer tumor cells.[9] This feature of cervical carcinoma makes patients potentially suitable for immunotherapy. Therefore, PD-1 (pembrolizumab, nivolumab, cemiplimab) and PD-L1 inhibitors (atezolizumab, avelumab, durvalumab) are being evaluated in other cervical cancer trials.

To date, pembrolizumab and nivolumab have been approved for the treatment of patients with relapsed or refractory metastatic squamous cell carcinoma of the cervix, following the results of the KEYNOTE-158,826 and CheckMate-358 studies. However, the two-phase double trials demonstrated the moderate antitumor activity of nivolumab[10] and pembrolizumab[11],[12] for recurrent or metastatic cervical carcinoma.

Therefore, further investigation of immunotherapy and target drugs in this setting is required.

Recently, immune checkpoint inhibitors, as demonstrated by the humanized monoclonal antibodies, have been extensively studied in various tumor types, showing that pembrolizumab and nivolumab target PD-1, whereas atezolizumab, durvalumab, and avelumab target PD-L1.[7] However, none of these drugs have obtained recent approval for patients with recurrent or metastatic cervical carcinoma.

Camrelizumab (SHR-1210) is a high-affinity, fully humanized IgG4-κ PD-1 monoclonal antibody that blocks the binding of PD-1 to its ligands. This report presents results from the phase II trials evaluating the safety and preliminary antitumor activity of camrelizumab combined with albumin-binding paclitaxel and cisplatin as first-line therapy for patients with recurrent or metastatic cervical carcinoma.


 > Subjects and Methods Top


Study design and participants

Phase 2, open-label, prospective study was conducted at the Shandong Cancer Hospital and Institute (Jinan, China). Women aged 30–71 years initially diagnosed with cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma had metastatic disease or locoregional recurrence, were unsuitable for surgery or radiotherapy (histologically or cytologically confirmed and assessed by trained pathologists at the research institution), and were eligible to partake in the study. Additionally, an Eastern Cooperative Oncology Group performance status of ≤1 and at least one measurable lesion were assessed using the Response Evaluation Criteria in Solid Tumors v. 1.1 (RECIST 1.1) by the investigators. This assessment included an estimated life expectancy of 3 months or more and adequate organ function (the following were calculated using the Cockcroft–Gault formula: white blood cell count, ≥3.0 × 109 cells per L; absolute neutrophil count, ≥1.5 × 109 cells per L; hemoglobin concentrations, ≥80 g/L; platelet cell count, ≥80 × 109 cells per L; total bilirubin concentration, <1.5 times the upper limit of normal [ULN]; aspartate transaminase and alanine transaminase concentrations, <2.5 times ULN [could be extended to 5× in case of liver metastases]; and creatinine clearance rate, >45 mL/min). This study was approved by the Ethical Committee of Shandong Cancer Hospital and Institute on September 4, 2019.

The key exclusion criteria included a history of or active autoimmune disease; other malignant diseases; medical conditions requiring immunosuppressive medications, including steroids, innate, or acquired immunodeficiency disease; autoimmune hepatitis or active CNS metastases; grade 3–4 cardiac insufficiency by NYHA standard or left ventricular ejection fraction displayed by color Doppler echocardiography; thyroid dysfunction; and previous treatment with anti-PD-1 or anti-PD-L1 antibodies.

Patients were required to have no previous systemic chemotherapy except for concurrent chemoradiotherapy in the study. Additional criteria for inclusion and exclusion are provided in the protocols.

The local institutional review board approved the trial protocol following the Declaration of Helsinki and Good Clinical Practice guidelines defined by the International Conference on Harmonization. Moreover, all patients provided written and informed consent before enrollment.

Procedures

During the trial, a maximum of six cycles of camrelizumab 200 mg was administered for 30 min on day 1 and albumin-binding paclitaxel 260 mg/m2 for 30 min on day 2. Additionally, carboplatin area under the curve of 5 (calculated by a radioisotope measurement of glomerular filtration rate) for 4 h on day 2 was intravenously administered every 3 weeks sequentially, followed by camrelizumab 200 mg maintenance therapy once every 3 weeks. The treatment was continued until the disease progressed, the patient withdrew, unacceptable toxic effects appeared, or death occurred. Furthermore, dose modifications of camrelizumab were not permitted. The administration of camrelizumab was interrupted if the patients had grade 3 or worse hematological adverse occurrences or grade 2 or worse nonhematological adverse events (AEs) (these were not defined as dose-limiting toxic effects). The severity of AEs was graded by investigators using NCI-CTC AE 4.0. The effectiveness evaluation was conducted every two cycles (the time was calculated based on calendar days and unaffected by the drug withdrawal) according to RECIST 1.1, with the evaluation time performed within 7 days at the end of the cycle (except statutory holidays). Also, evaluation should be performed by CT or MRI; the same imaging techniques should be employed in the preevaluation and postevaluation of the same patient, and all imaging data should be retained. The subjects whose therapeutic effects reached complete response (CR), partial response (PR), and SD need to be re-examined and confirmed 4 weeks after the first evaluation.

Outcomes

Objective response rate (ORR) and disease control rate (DCR). ORR refers to the proportion of patients whose tumors shrink to certain levels and maintain a certain time, including CR and PR cases. DCR was defined as the proportion of patients who achieved a CR, a PR, or stable disease. The secondary outcomes were duration of response (DoR) and safety. DoR refers to dates of PD or death from the first CR or PR. Also, the safety of the treatment was evaluated by the occurrence of AEs and the severity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v. 4.0.

Statistical analysis

The data cutoff date for this analysis was April 30, 2020. Data were expressed as mean ± standard deviation, median (minimum–maximum), frequency (constituent ratio), and rate with confidence interval (CI) where appropriate. Also, response and disease progression were expressed as rate (%) with 95% CI. The treatment efficacy was analyzed in the per-protocol set (PPS), and safety was analyzed in the safety set (SS). SPSS v. 22.0 was used for all analyses. This study is registered with the Chinese Clinical Trial Registry, ChiCTR1900025992.


 > Results and Discussion Top


A total of 35 patients were enrolled in the study, and their baseline characteristics are presented in [Table 1]. All 35 patients were treated with the study medication at least once, and their safety data was recorded. They were also included in the SS for safety analysis. In addition, 27 patients were treated according to the protocol and then included in the PPS for efficacy analysis.
Table 1: Baseline characteristics of all enrolled patients

Click here to view


Till the data cutoff, the median follow-up was 4.53 (0.72–10.97) months until the data cutoff. Also, only two (7.41%) patients had disease progression, two (7.41) died, and three (11.11%) were lost to follow-up. CR, PR, SD was achieved in 4 (14.81%), 6 (22.22%), and 13 (48.15%) patients, respectively. The ORR and DCR were 40.00% (95% CI: 21.13–61.33%) and 92.00% (95% CI: 73.97–99.01%), respectively. These details are presented in [Table 2]. Also, the best percentage change for each patient is shown in [Figure 1].
Table 2: Response rate, disease progression (based on PPS)

Click here to view
Figure 1: Waterfall plot of the best percent change from baseline in target lesion size (based on PPS)

Click here to view


–7.60) months [Figure 2]. The most common AEs were reactive cutaneous capillary endothelial proliferation (RCCEP), observed in 23 (65.71%) patients, followed by gastrointestinal reaction (8, 22.86%) and fever (8, 22.86%). Also, grade 3 AEs included five (14.29%) myelosuppression, and grade four AEs included 1 (2.86%) RCCEP and one (2.86%) bladder inflammation. The detailed AEs are presented in [Table 3].
Table 3: Overview of adverse events (based on SS)

Click here to view
Figure 2: Kaplan–Meier plot of duration of response

Click here to view


In this report, assessed the combined therapy of camrelizumab and albumin-binding paclitaxel with carboplatin in patients with metastatic or recurrent cervical cancer. Our results indicated that the addition of camrelizumab to chemotherapy with albumin-binding paclitaxel and carboplatin for these patients showed a favorable antitumor activity. We also observed that 40% (95% CI 21.13–61.33%) of the patients achieved an objective response, and the DCR has reached 92% (95% CI 73.97–99.01%). Furthermore, the combination of the regime showed a manageable toxicity profile.

Although cervical carcinoma is a chemosensitive tumor, a high proportion of patients with recurrent or metastatic cervical carcinoma can respond with platinum-based chemotherapy regimens during the first-line treatment, with patients who are persistent or progress after chemotherapy having few treatment options.[13] In this setting, salvage chemotherapy and targeted drugs produce a moderate antitumor activity as second-line or later treatment.[4],[14],[15],[16],[17],[18],[19] Compared with traditional medicines, albumin-bound paclitaxel is more efficient and less toxic.[20],[21],[22],[23] A phase II study demonstrated that albumin-bound paclitaxel was effective in the second-line treatment of recurrent or persistent advanced cervical cancer, with an ORR and DCR of 28.6 and 71.5%, respectively.[24] In addition, a subgroup analysis of another phase II study showed that the ORR of albumin-bound paclitaxel combined with nedaplatin in the first-line treatment of cervical cancer was as high as 66.7%.[16] Only small studies in cervical carcinoma have been published for the immune checkpoint inhibitors. In the CheckMate 358 trial,[25] the ORR was 26.3% (95% CI, 9.1–51.2) for cervical cancer, and the median overall survival was 21.9 months (95% CI, 15.1 months to not reached) among patients with cervical cancer. In the KEYNOTE-028 trial,[26] the overall response rate was 17% (95% CI, 5–37%), and the DCR was 30%.

Whether pembrolizumab or nivolumab alone showed minimal activity in women with recurrent cervical cancer, the combination of immunity and chemotherapy could show good antitumor activity potential in patients with recurrent cervical cancer. Interestingly, in the KEYNOTE-189 study,[27],[28] frontline pembrolizumab combined with pemetrexed and carboplatin improved the overall survival of advanced nonsquamous cell lung cancer, irrespective of the PD-L1 expression level. This combined approach is currently investigated in various cancer types.[29],[30],[31] In this study, the combination of camrelizumab and albumin-bound paclitaxel and carboplatin as first-line treatment in recurrent or metastatic cervical carcinoma led to a proportion of 40.00% (95% CI 21.13–61.33) patients with objective response and 92.00% (73.97–99.01) of patients achieving disease control, including 14.81% (4/27 patients) CR and 22.22% (6/27 patients) PR. Also, the tumor shrinkage was large, and the response was durable. The results of this trial provide support for further assessment of this combination approach in phase 3 studies.

Additionally, fatigue and hypothyroidism are considered to be the most common AEs related to immunotherapy agents. Importantly, a frequent AE, capillary hemangioma with the hyperproliferative vascular response, was observed in about two-thirds of patients in our group, as previously reported in patients with both advanced esophageal and recurrent nasopharyngeal carcinoma treated with camrelizumab.[32],[33] Although neutropenia and anemia were the top grade 3 hematological toxicities caused by albumin-bound paclitaxel and carboplatin, there was no treatment-related death. These data revealed that camrelizumab combined with albumin-bound paclitaxel and carboplatin regimen is generally manageable in patients with recurrent or metastatic cervical carcinoma.

Its inadequate validation with randomization and the small sample size of patients treated with camrelizumab plus albumin-bound paclitaxel and carboplatin. Therefore, a phase 3 randomized, placebo-controlled trial will be needed to validate the results of the current study. In addition, this study was conducted in Chinese patients only, causing the results to differ from different ethnic groups. Finally, there is no clear basis for determining patient type that benefits from immunotherapy and a small amount of data supporting the PD-1-positive patients and microsatellite instability results. Our research results also support this point. We also analyze and compare the blood and tissue samples of patients with good or poor effects, hoping to find sensitive indicators to this treatment regimen.

Conclusively, our study demonstrated that the combination therapy of camrelizumab and albumin-bound paclitaxel and carboplatin had significant efficacy and manageable toxicities in patients with recurrent or metastatic cervical cancer; therefore, further study in phase 3 trials is warranted.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.  Back to cited text no. 1
    
2.
Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, et al. The global burden of cancer 2013. JAMA Oncol 2015;1:505-27.  Back to cited text no. 2
    
3.
Thigpen T, Shingleton H, Homesley H, Lagasse L, Blessing J. Cis-platinum in treatment of advanced or recurrent squamous cell carcinoma of the cervix: A phase II study of the gynecologic oncology group. Cancer 1981;48:899-903.  Back to cited text no. 3
    
4.
Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, et al. Bevacizumab for advanced cervical cancer: Final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (gynecologic oncology group 240). Lancet (London, England) 2017;390:1654-63.  Back to cited text no. 4
    
5.
Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014;370:734-43.  Back to cited text no. 5
    
6.
Greer BE, Koh WJ, Abu-Rustum NR, Apte SM, Campos SM, Chan J, et al. Cervical cancer. J Natl Comp Canc Netw 2010;8:1388-416.  Back to cited text no. 6
    
7.
Heymach J, Krilov L, Alberg A, Baxter N, Chang SM, Corcoran RB, et al. Clinical cancer advances 2018: Annual report on progress against cancer from the American society of clinical oncology. J Clin Oncol 2018;36:1020-44.  Back to cited text no. 7
    
8.
Kumar L, Harish P, Malik PS, Khurana S. Chemotherapy and targeted therapy in the management of cervical cancer. Curr Probl Cancer 2018;42:120-8.  Back to cited text no. 8
    
9.
Yang W, Lu YP, Yang YZ, Kang JR, Jin YD, Wang HW. Expressions of programmed death (PD)-1 and PD-1 ligand (PD-L1) in cervical intraepithelial neoplasia and cervical squamous cell carcinomas are of prognostic value and associated with human papillomavirus status. J Obstet Gynaecol Res 2017;43:1602-12.  Back to cited text no. 9
    
10.
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1-10. doi: 10.1016/0197-2456(89)90015-9.  Back to cited text no. 10
    
11.
Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol 2019;37:1470-8.  Back to cited text no. 11
    
12.
Shapira-Frommer R, Alexandre J, Monk B, Fehm T, Colombo N, Caceres M, et al. KEYNOTE-826: A phase 3, randomized, double-blind, placebo-controlled study of pembrolizumab plus chemotherapy for first-line treatment of persistent, recurrent, or metastatic cervical cancer. J Clin Oncol 2019;37:TPS5595-TPS. doi: 10.1200/JCO.2019.37.15_suppl.TPS5595.  Back to cited text no. 12
    
13.
Boussios S, Seraj E, Zarkavelis G, Petrakis D, Kollas A, Kafantari A, et al. Management of patients with recurrent/advanced cervical cancer beyond first line platinum regimens: Where do we stand? A literature review. Crit Rev Oncol Hematol 2016;108:164-74.  Back to cited text no. 13
    
14.
Pignata S, Scambia G, Lorusso D, De Giorgi U, Nicoletto MO, Lauria R, et al. The MITO CERV-2 trial: A randomized phase II study of cetuximab plus carboplatin and paclitaxel, in advanced or recurrent cervical cancer. Gynecol Oncol 2019;153:535-40.  Back to cited text no. 14
    
15.
Suzuki K, Nagao S, Shibutani T, Yamamoto K, Jimi T, Yano H, et al. Phase II trial of paclitaxel, carboplatin, and bevacizumab for advanced or recurrent cervical cancer. Gynecol Oncol 2019;154:554-7.  Back to cited text no. 15
    
16.
Li Y, Zeng J, Huang M, An J, Bai P, Wu L, et al. A phase 2 study of nanoparticle albumin-bound paclitaxel plus nedaplatin for patients with advanced, recurrent, or metastatic cervical carcinoma. Cancer 2017;123:420-5.  Back to cited text no. 16
    
17.
Chan JK, Deng W, Higgins RV, Tewari KS, Bonebrake AJ, Hicks M, et al. A phase II evaluation of brivanib in the treatment of persistent or recurrent carcinoma of the cervix: An NRG oncology/gynecologic oncology group study. Gynecol Oncol 2017;146:554-9.  Back to cited text no. 17
    
18.
Thaker PH, Salani R, Brady WE, Lankes HA, Cohn DE, Mutch DG, et al. A phase I trial of paclitaxel, cisplatin, and veliparib in the treatment of persistent or recurrent carcinoma of the cervix: An NRG oncology study (NCT#01281852). Ann Oncol 2017;28:505-11.  Back to cited text no. 18
    
19.
Aoki Y, Ochiai K, Lim S, Aoki D, Kamiura S, Lin H, et al. Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer. Br J Cancer 2018;119:530-7.  Back to cited text no. 19
    
20.
Miaomiao Y, Huajun Q, Aina L, Jiannan L, Ping S, Hua L. Efficacy and safety of nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy in HER2-negative breast cancer. J Cancer Res Ther 2019;15:1561-6.  Back to cited text no. 20
    
21.
Shuanggang C, Xiaoshi Z, Lujun S, Han Q, Weimei M, Cao F, et al. Transcatheter arterial infusion of anti-programmed cell death 1 antibody pembrolizumab combined with temozolomide or nab-paclitaxel in patient with primary anorectal malignant melanoma: Four case reports. J Cancer Res Ther 2020;16:387-92.  Back to cited text no. 21
    
22.
Ana FM, Paula GV, Manuel VA, Juan DG, Guillermo QA, Tuñas LV, et al. Prognostic and predictive markers of response to treatment in patients with locally advanced unresectable and metastatic pancreatic adenocarcinoma treated with gemcitabine/nab-paclitaxel: Results of a retrospective analysis. J Cancer Res Ther 2017;13:240-5.  Back to cited text no. 22
    
23.
Casanova-Martinez C, Yaiza Romero-Ventosa E, González-Costas S, Arroyo-Conde C , Piñeiro-Corrales G. Evaluation of the use of nab-paclitaxel and gemcitabine in clinical practice. J Cancer Res Ther 2018;(Suppl):S730-5.  Back to cited text no. 23
    
24.
Alberts DS, Blessing JA, Landrum LM, Warshal DP, Martin LP, Rose SL, et al. Phase II trial of nab-paclitaxel in the treatment of recurrent or persistent advanced cervix cancer: A gynecologic oncology group study. Gynecol Oncol 2012;127:451-5.  Back to cited text no. 24
    
25.
Naumann RW, Hollebecque A, Meyer T, Devlin MJ, Oaknin A, Kerger J, et al. Safety and efficacy of nivolumab monotherapy in recurrent or metastatic cervical, vaginal, or vulvar carcinoma: Results from the phase I/II checkmate 358 trial. J Clin Oncol 2019;37:2825-34.  Back to cited text no. 25
    
26.
Frenel JS, Le Tourneau C, O'Neil B, Ott PA, Piha-Paul SA, Gomez-Roca C, et al. Safety and efficacy of pembrolizumab in advanced, programmed death ligand 1-positive cervical cancer: Results from the phase Ib KEYNOTE-028 trial. J Clin Oncol 2017;35:4035-41.  Back to cited text no. 26
    
27.
Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018;378:2078-92.  Back to cited text no. 27
    
28.
Gadgeel S, Rodríguez-Abreu D, Speranza G, Esteban E, Felip E, Dómine M, et al. Updated analysis from KEYNOTE-189: Pembrolizumab or placebo plus pemetrexed and platinum for previously untreated metastatic nonsquamous non-small-cell lung cancer. J Clin Oncol 2020;38:1505-17.  Back to cited text no. 28
    
29.
Fujimoto N, Aoe K, Kozuki T, Oze I, Kato K, Kishimoto T, et al. A phase II trial of first-line combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma: A study protocol. Clin Lung Cancer 2018;19:e705-7.  Back to cited text no. 29
    
30.
Rizvi NA, Hellmann MD, Brahmer JR, Juergens RA, Borghaei H, Gettinger S, et al. Nivolumab in combination with platinum-based doublet chemotherapy for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 2016;34:2969-79.  Back to cited text no. 30
    
31.
Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, et al. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: Results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer 2019;22:828-37.  Back to cited text no. 31
    
32.
Huang J, Xu B, Mo H, Zhang W, Chen X, Wu D, et al. Safety, activity, and biomarkers of SHR-1210, an anti-PD-1 antibody, for patients with advanced esophageal carcinoma. Clin Cancer Res 2018;24:1296-304.  Back to cited text no. 32
    
33.
Fang W, Yang Y, Ma Y, Hong S, Lin L, He X, et al. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: Results from two single-arm, phase 1 trials. Lancet Oncol 2018;19:1338-50.  Back to cited text no. 33
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Subjects and Methods>Results and Disc...>Article Figures>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed168    
    Printed4    
    Emailed0    
    PDF Downloaded36    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]