Pembrolizumab monotherapy versus pembrolizumab plus chemotherapy in patients with non‐small‐cell lung cancer: A multicenter retrospective trial

Matsumoto, Hiromi; Kobayashi, Nobuaki; Somekawa, Kohei; Fukuda, Naoto; Kaneko, Ayami; Kamimaki, Chisato; Kubo, Sousuke; Tanaka, Katsushi; Tagami, Yoichi; Teranishi, Shuhei; Watanabe, Keisuke; Horita, Nobuyuki; Hara, Yu; Yamamoto, Masaki; Kudo, Makoto; Koizumi, Harumi; Miura, Kenji; Miyazawa, Naoki; Kaneko, Takeshi

doi:10.1111/1759-7714.14252

Cited by 11 publications

(9 citation statements)

References 28 publications

(44 reference statements)

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“…In clinical practice, targeted therapy, radiotherapy, and chemotherapy combined with immunotherapy have been applied successfully in various tumors. 431 – 433 Therefore, we summarized clinical trials of some novel autophagy, pyroptosis, ferroptosis, and necroptosis inducers/inhibitors, chemotherapy, radiotherapy, and targeted therapy combined with immunotherapy (Table 3 ).…”

Section: New Advances In Targeting Autophagy Pyroptosis Ferroptosis A...mentioning

confidence: 99%

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Gao

Wang

Zhou

et al. 2022

Sig Transduct Target Ther

466

189

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In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not to ICIs, partly caused by the absence of tumor-infiltrating lymphocytes (TILs), significantly limits the application of ICIs. Converting these immune “cold” tumors into “hot” tumors that may respond to ICIs is an unsolved question in cancer immunotherapy. Since it is a general characteristic of cancers to resist apoptosis, induction of non-apoptotic regulated cell death (RCD) is emerging as a new cancer treatment strategy. Recently, several studies have revealed the interaction between non-apoptotic RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, and necroptosis exhibit synergistic antitumor immune responses while possibly exerting inhibitory effects on antitumor immune responses. Thus, targeted therapies (inducers or inhibitors) against autophagy, ferroptosis, pyroptosis, and necroptosis in combination with immunotherapy may exert potent antitumor activity, even in tumors resistant to ICIs. This review summarizes the multilevel relationship between antitumor immunity and non-apoptotic RCD, including autophagy, ferroptosis, pyroptosis, and necroptosis, and the potential targeting application of non-apoptotic RCD to improve the efficacy of immunotherapy in malignancy.

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Section: New Advances In Targeting Autophagy Pyroptosis Ferroptosis A...mentioning

confidence: 99%

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Gao

Wang

Zhou

et al. 2022

Sig Transduct Target Ther

466

189

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“…Although the study results favored combination therapy, subsequent real-world studies demonstrated similar PFS and OS among patients who received different treatment modalities [11,12,14]. On the contrary, a multicenter retrospective cohort study conducted by Matsumoto et al showed that pembrolizumab monotherapy provided longer PFS than combination therapy in the subgroup of patients with metastases to the liver, lung, adrenal glands, bone, or lymph nodes [13]. Moreover, a retrospective study using electronic databases of four Israeli cancer centers showed that pembrolizumab monotherapy and combination therapy with pembrolizumab and chemotherapy provided similar OS in patients with high PD-L1 expression after propensity score matching, and a significantly longer median OS was observed only in female patients who received the combination therapy [11].…”

Section: Discussionmentioning

confidence: 95%

“…Recently, cohort studies comparing treatment efficacy of pembrolizumab alone or in combination with chemotherapy have been carried out, but no significant difference in survival outcomes was observed amongst patients who received different treatment modalities [11][12][13][14]. The possible reasons for the insignificant difference might be attributed to the higher toxicities in combination therapy [14] and its limited clinical benefits in certain patient subgroups [11].…”

Section: Introductionmentioning

confidence: 99%

Pembrolizumab and Chemotherapy Combination Prolonged Progression-Free Survival in Patients with NSCLC with High PD-L1 Expression and Low Neutrophil-to-Lymphocyte Ratio

et al. 2022

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The use of immune checkpoint inhibitors (ICIs) has provided overall survival (OS) benefits in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, studies comparing ICIs monotherapy with combination therapy either with chemotherapy or radiotherapy in programmed death-ligand 1 high expressors remain limited. This study aimed to retrospectively compare the treatment efficacy of the therapies by studying 47 patients with treatment-naïve advanced NSCLC who received ICI monotherapy (n = 28) or combination therapy either with chemotherapy or radiotherapy (n = 19). Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method and compared using log–rank tests. It was observed that patients who received combination therapy had a better PFS than monotherapy, but no such significant benefit was observed in OS. The difference in PFS was higher in the subgroup of patients with low neutrophil-to-lymphocyte ratio (NLR) than in the high-NLR patient subgroup. This study suggests that pembrolizumab in combination with chemotherapy or radiotherapy could provide a significant benefit in PFS, especially in patients with treatment-naïve advanced NSCLC with low NLR. Furthermore, our study also demonstrates the potential use of NLR as a biomarker for prediction of treatment outcomes in patients with advanced NSCLC receiving combination therapy.

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“…Pembrolizumab is the first-line therapy for patients with PD-L1 50% or greater as when pembrolizumab is used as monotherapy there were no significant differences in PFS, OS and respond rate (RR) compared to pembrolizumab combined with chemotherapy and pembrolizumab (2 mg/kg every 3 weeks or 10 mg/kg every 2 or 3 weeks) showed 3-year OS rate in 35% of patients who received pembrolizumab compared to13% of patients who received docetaxel (chemotherapy) [27,28]. Pembrolizumab showed 5-year OS for patients who have PD-L1 50% or greater either these patients are previously treated patients or treatmentnaive patients and only grade 3 adverse events occurred, and grade 4 adverse events aren't documented [29].…”

Section: Pembrolizumabmentioning

confidence: 98%

Immunotherapy, Immunobiomarkers and Gene Analysis Role in the Improvement of Lung Cancer Treatment

Wael¹,

Hosam²,

Youssef³

et al. 2022

RCO

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Lung cancer is the second most common cancer with a poor survival rate (18.6%). Recently treatment of lung cancer has been improved starting from choosing appropriate treatment by gene and immunobiomarkers analysis to immunotherapy which played a major role in the treatment of lung cancer and showed improvement in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) with less adverse effects. Through this triad Immunotherapy, immunobiomarkers and Gene analysis oncologists can provide better treatment for lung cancer patients. The most important cause that makes immunotherapy shows good results in the treatment of lung cancer is P53 gene mutation which is present in more than half of lung cancer patients. P53 gene mutation causes high genetic instability so causes more mutations in cancer cells and more neoantigens are formed. These neoantigens make cancer cells more immunogenic and respond better to the treatment of lung cancer by immunotherapy. The most common immunotherapy drug family that is effective in the treatment of lung cancer is Immune checkpoint inhibitors. Throughout the journey of treatment Immune checkpoint inhibitors can develop resistance by multiple mechanisms that are discussed in the review and to overcome these mechanisms Immune checkpoint inhibitors can be used in combination with other immunotherapies or radiotherapy.

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Pembrolizumab monotherapy versus pembrolizumab plus chemotherapy in patients with non‐small‐cell lung cancer: A multicenter retrospective trial

Cited by 11 publications

References 28 publications

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Pembrolizumab and Chemotherapy Combination Prolonged Progression-Free Survival in Patients with NSCLC with High PD-L1 Expression and Low Neutrophil-to-Lymphocyte Ratio

Immunotherapy, Immunobiomarkers and Gene Analysis Role in the Improvement of Lung Cancer Treatment

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