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ORIGINAL ARTICLE
Year : 2022  |  Volume : 18  |  Issue : 2  |  Page : 576-580

Effectiveness and safety of camrelizumab combined with chemotherapy in nonsquamous nonsmall cell lung cancer as the second-line therapy: A retrospective analysis


Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

Date of Submission27-May-2021
Date of Acceptance10-Nov-2021
Date of Web Publication20-May-2022

Correspondence Address:
Congjun Zhang
Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.jcrt_855_21

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 > Abstract 


Background: The role of camrelizumab combined with chemotherapy as the second-line therapy in nonsquamous nonsmall cell lung cancer (NSCLC) remains unverified. The retrospective study investigated efficacy and safety of camrelizumab combined with chemotherapy in the treatment of nonsquamous NSCLC as the second-line therapy.
Subjects and Methods: Patients of nonsquamous NSCLC who were already discharged or died of the First Affiliated Hospital of Anhui Medical University between August 2019 and September 2020. According to the treatment method, the patients who received chemotherapy were denoted as the C group and those who received camrelizumab plus chemotherapy were denoted as the C&C group.
Statistical Analysis Used: Patients responses were statistically analyzed. The Cox proportional hazards regression model was used in the assessment of the prognostic value of factors. Furthermore, adverse event evaluation was estimated.
Results: Of the 60 patients with nonsquamous NSCLC included in the research, 29 patients received chemotherapy, and 31 patients received camrelizumab plus chemotherapy. The objective response rate was 13.79% and 32.26% for chemotherapy and camrelizumab plus chemotherapy groups, and the disease control rate was 72.41% and 80.65%. The median progression-free survival (mPFS) in camrelizumab plus chemotherapy group was obviously higher than that in the chemotherapy group (9.67 vs. 6.87 months, P = 0.01). The median overall survival of the camrelizumab plus chemotherapy was longer than the chemotherapy (10.89 vs. 7.95 months, P < 0.01). In the current treatment, radiotherapy and smoking were independent risk factors for the mPFS of patients with nonsquamous NSCLC. The occurrence of adverse events was similar between chemotherapy and camrelizumab plus chemotherapy groups.
Conclusions: Camrelizumab combined with chemotherapy was an effective regimen with manageable toxicity in treating nonsquamous NSCLC as the second-line therapy.

Keywords: Camrelizumab, combined chemotherapy, nonsquamous nonsmall cell lung cancer, second line


How to cite this article:
Huang W, Zhang Q, Da L, Shen Y, Xiong F, Zhang C. Effectiveness and safety of camrelizumab combined with chemotherapy in nonsquamous nonsmall cell lung cancer as the second-line therapy: A retrospective analysis. J Can Res Ther 2022;18:576-80

How to cite this URL:
Huang W, Zhang Q, Da L, Shen Y, Xiong F, Zhang C. Effectiveness and safety of camrelizumab combined with chemotherapy in nonsquamous nonsmall cell lung cancer as the second-line therapy: A retrospective analysis. J Can Res Ther [serial online] 2022 [cited 2022 Jul 7];18:576-80. Available from: https://www.cancerjournal.net/text.asp?2022/18/2/576/345547




 > Introduction Top


Nonsmall cell lung cancer (NSCLC) is the most common malignant tumor, accounting for approximately 85% of lung cancers and had the more frequent incidences among smokers.[1],[2] NSCLC patients at early and medium stages, who could benefit from surgical resection, were often ignored due to the lack of a reliable screening method.[3] Therefore, nonsurgical treatment became the better choice for patients with more advanced diseases.[4] Clinically, platinum-based chemotherapy is always the standard of care for advanced NSCLC patients.[5] However, it always resulted in failure of treatment due to the unsatisfactory response rate, low median survival time, and drug resistance, particularly in second-line treatment.[6] Thus, exploring the definite therapeutic effects, high-security therapy strategies are crucial to NSCLC patients.

Over the last decade, the role of Immune-checkpoint inhibitors (ICI), especially inhibitors of the programmed death-1 (PD-1) axis, could significantly improve the outcomes in second-line advanced diseases and alter the treatment of NSCLC.[7] Camrelizumab, a high-affinity, humanized, IgG4-κ PD-1 monoclonal antibody, developed by Jiangsu Hengrui Medicine Co. Ltd., is capable of indicating for treating various malignancies.[8] Wei et al. demonstrated that camrelizumab improved the objective response rate (ORR) in the advanced NSCLC patients.[9] However, the application of PD-1 antibodies was limited as a result of the low response rate. Furthermore, clinical reporters indicated that camrelizumab in combination with chemotherapy was a superior treatment option in advanced cancer, such as advanced esophageal squamous cell carcinoma.[10] To date, no report explored the combination of camrelizumab and chemotherapy as a second-line therapy for nonsquamous NSCLC. Hence, this study explores the efficacy and safety of camrelizumab combined with chemotherapy in the treatment of nonsquamous NSCLC as the second-line therapy.


 > Subjects and Methods Top


Ethics

This retrospective study was conducted following the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University. An informed consent was obtained from the patients on their initial admission. The data were gathered in the context of standard practice from clinical patient records without an informed consent. Then, the data were anonymized and stored in a protected database.

Patients

The retrospective analysis was collected the medical records of patients of nonsquamous NSCLC who were already discharged or died between August 2019 and September 2020. The inclusion criteria were as follows: patients diagnosed with nonsquamous NSCLC pathologically or histologically; patients aged ≥45; nonsquamous NSCLC patients who failed the first-line therapy; expected survival time of patients >3 months. The exclusion criteria were as follows: patients with severe insufficiency of liver and kidney function; the duration of using other medications <4 weeks; lactating or pregnant woman.

Study design and treatment

The eligible patients received the chemotherapy or Camrelizumab plus chemotherapy. The chemotherapy regimens included paclitaxel (Jiangsu Hengrui Pharmaceuticals Co., Ltd., Jiangsu, China), lobaplatin (Hainan Changan International Pharmaceutical Co., Ltd., Hainan, China), oxaliplatin (Jiangsu Hengrui Pharmaceuticals Co., Ltd., Jiangsu, China), cisplatin (Qilu Pharmaceutical Co., Ltd., Shandong, China), ifosfamide (Jiangsu Hengrui Pharmaceuticals Co., Ltd., Jiangsu, China) + carboplatin (Qilu Pharmaceutical Co., Ltd., Shandong, China), gemcitabine (Jiangsu Hengrui Pharmaceuticals Co., Ltd., Jiangsu, China) + paclitaxel, and pemetrexed (Qilu Pharmaceutical Co., Ltd., Shandong, China) + cisplatin. Camrelizumab (Jiangsu Hengrui Pharmaceuticals Co., Ltd., Jiangsu, China) was administered (200-mg) once a day. A cycle of treatment consisted of 21 days

Data collection

The baseline data included gender, age, smoking history, and so on. According to the response evaluation criteria in solid tumors 1.1 criteria, the responses are classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The ORR = CRs + PRs; disease control rate (DCR) = PRs + SDs. Overall survival (OS) means from the time of entry to death (any reason). Progression-free survival (PFS) refers to the date of entry to the date of disease progression or death from any cause. According to the Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0), and the typical image of a patient scanned by computed tomography (CT) scan patients were provided in [Supplement Figure 1].



Statistical analysis

The data were analyzed using SPSS software 25 version (International Business Machines Corp., New York, America). Furthermore, the rates were calculated using Chi-square test. Kaplan–Meier methodology was used to estimate the OS and PFS. Cox proportional hazard model was used to analyze the independent risk factors.


 > Results Top


Patient characteristics

Between August 2019 and September 2020, the characteristics of 60 patients with the nonsquamous NSCLC were listed in [Table 1]. The patients consist of 41 (68.33%) male and 19 (31.67%) female patients with a mean age of 55.7 years old. Besides, 32 patients showed an Eastern Cooperative Oncology Group performance status of 0 (66.23%) and 1 (28, 46.67%), respectively, and 24 (40.00%) patients accepted surgical treatment, while the other 36 (60.00%) patients did not. Thirty-three patients (55.00%) were undergoing radiotherapy, while 27 (45.00%) were not. In addition, a total of 51.67% of patients had current or former history. The patients were diagnosed with nonsquamous NSCLC, lung adenocarcinoma was identified in 85.00% of the patients, and 15.00% were magnocellular carcinoma of the lung. The patients who received chemotherapy were regarded as the C group, and those who received camrelizumab plus chemotherapy were regarded as the C&C group. There were no significant difference in baseline characteristics between the chemotherapy and camrelizumab plus chemotherapy groups.
Table 1: Baseline characteristics of patients

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Effectiveness

The patients treated with camrelizumab plus chemotherapy accepted the imaging examination. As shown in [Table 2], the ORR was 13.79% and 32.26% for chemotherapy and camrelizumab plus chemotherapy groups, and the DCR was 72.41% and 80.65%. Although there was no significant difference, it could be found that camrelizumab plus chemotherapy groups had trends to increase the ORR and DCR compared with the chemotherapy group. Specifically, three patients had achieved CR in camrelizumab plus chemotherapy groups but zero in chemotherapy groups. Moreover, most patients had achieved SD, which were 17 (24.14%) and 20 (65.42%) in chemotherapy and camrelizumab plus chemotherapy groups, respectively.
Table 2: Response of patients to camrelizumab plus chemotherapy in the second-line therapy

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As shown in [Table 3] and [Figure 1], for the survival outcome, the median PFS (mPFS) in camrelizumab plus chemotherapy group was higher than in the chemotherapy group (9.67 vs. 6.87 months, P = 0.01), and the 6-month PFS rate and 12-month PFS rate in camrelizumab plus chemotherapy group were also higher than in camrelizumab plus chemotherapy group (28.57% vs. 10.00%, P = 0.307; 48.15% vs. 23.08%, P < 0.01). The median OS (mOS) of the camrelizumab plus chemotherapy was longer than chemotherapy (10.89 vs. 7.95 months, P < 0.01). Besides, a trend was observed with longer 6-month in camrelizumab plus chemotherapy group compared with the chemotherapy group (33.33% vs. 28.57%, P = 0.420), and 12-months OS of camrelizumab plus chemotherapy was significantly longer than that of chemotherapy (55.56% vs. 34.62%, P < 0.01).
Table 3: Survival analysis of patients to chemotherapy and camrelizumab plus chemotherapy

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Figure 1: The survival outcome of patients for chemotherapy and camrelizumab plus chemotherapy. (a) The progression-free survival time of the two therapy. (b) The overall survival time of the two therapy. The black dotted line represented the medium survival time

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Cox proportional hazard regression analysis

In univariate analysis, current treatment (chemotherapy or camrelizumab plus chemotherapy), surgery, gender, smoking, chemotherapy, and ages were selected from the Cox proportional hazard model for multivariate analysis. Moreover, the multivariate analysis showed that current treatment, radiotherapy, and smoking were the independent risk factor for the mPFS of patients with nonsquamous NSCLC [Table 4].
Table 4: Cox regression model

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Safety

Forty-three patients experienced adverse events. The incidence of the adverse events (AE) achieved 71.67%. Among them, the incidence of grade ≥3AEs was 18.33%. As is shown in [Table 5], the incidence of anemia, thrombocytopenia, cough, proteinuria, reactive cutaneous capillary endothelial proliferation (RCCEP), and leukocytopenia in the two groups were conducted, indicating a similarity between chemotherapy and camrelizumab plus chemotherapy groups.
Table 5: The incidence of Grade HR=adverse events of nonsquamous nonsquamous nonsmall cell lung cancer patients

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 > Discussion Top


PD-1 antibodies have been used in many advanced cancers and exhibited satisfactory treatment effect.[11],[12] Camrelizumab as a human PD-1 antibody was approved as the second-line drug for nonsquamous NSCLC in China.[13] Furthermore, chemotherapy remains the standard treatment for the second-line management of NSCLC.[14] Therefore, we present camrelizumab combined with chemotherapy as the second-line therapy in nonsquamous NSCLC. In the analysis of a clinical trial, the mPFS and OS of apatinib plus camrelizumab were 5.7 months and 15.5 months, respectively, showing encouraging antitumor activity in the treatment of nonsquamous NSCLC.[15] In another phase III study, chemotherapy plus camrelizumab was compared with chemotherapy as a first-line treatment option for Chinese nonsquamous NSCLC patients, and the PFS was 11.3 and 8.3 months.[16] Similarly, our data showed that patients who received the camrelizumab combined with chemotherapy achieved the longer mPFS (9.67 vs. 6.87 months) and mOS (10.89 vs. 7.95 months) than chemotherapy. These results suggested camrelizumab combined with chemotherapy had a trend of survival benefit.

The Cox regression model was used to further discover that smoking, camrelizumab combined with chemotherapy or chemotherapy, and chemotherapy history were the independent risk factors for the mPFS of patients with nonsquamous NSCLC, to exclude the effect of the confounders for survival outcome. Some researches had concluded that smoking promoted the incidence of mutations in somatic cells, which may explained the high incidence of the disease among smokers.[17] A study of 5229 patients with lung cancer showed that the median survival of nonsmokers, former smokers, and current smokers was 1.4, 1, 3, and 1.1 years (P < 0.01), and the relative risk per 10 years of smoking abstinence was 0.85.[18] In other word, smoking was a risk factor for the survival of lung cancer patients. This study also indicated that smoking was the independent risk factor for the mPFS of patients with nonsquamous NSCLC (hazard ratio [HR]: 3.826, 95% confidence interval [CI]: 1.193–12.269, P = 0.024). Besides, Yang et al. reported that PD-1 antibody combined with pemetrexed and platinum prolonged the mPFS than placebo-combination (8.9 vs. 5.0 months; HR: 0.482).[19] In the multivariate Cox model, HR of camrelizumab plus chemotherapy compared with chemotherapy achieved 0.196 (95% CI: 0.080–0.477, P < 0.001). In addition, HR of patients who received the radiotherapy previously compared with those who had not received radiotherapy previously achieved 0.305 (95% CI: 0.112–0.829, P = 0.020). This finding cohered with Narek opinion of Shaverdian et al. who reported that treatment with radiotherapy before in the patients with NSCLC resulted in longer PFS and OS with pembrolizumab.[20] In addition, substantial data has accumulated suggesting that radiotherapy stimulates the systemic immune response, which might have induced the activation and migration of dendritic cells and increased that antigen presentation by dendritic cells, finally enhancing the recognition and activity of antitumor T-cell.[21],[22],[23]

Adverse events usually occur in the treatment of NSCLC, such as anemia, thrombocytopenia, and cough, with the RECCP being the most common, which were all observed in the treatment of camrelizumab plus chemotherapy or chemotherapy.[24],[25],[26] Specifically, the application of PD-1 antibody activated the immune response and promoted the differentiation of macrophages with the proliferation of blood capillary endothelial cells, finally causing the RCCEP.[27] However, a clinical trial found that it was management and reversible.[28]

Conclusion

In conclusion, the analysis of this study shows that Camrelizumab combined with chemotherapy as a second-line treatment for nonsquamous NSCLC is an effective and toxicity controllable scheme. However, further well-designed and larger sample size studies are needed to confirm the results.

Acknowledgment

This research was approved by Bethune Foundation for Medical Science Research (NO. B19067ET).

Data availability

All data generated or analyzed during this study are included in this published article.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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