Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenva...Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.展开更多
Immune checkpoint inhibitors(and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab)initiated a revolution in the field of melanoma and have now expanded to several tu...Immune checkpoint inhibitors(and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab)initiated a revolution in the field of melanoma and have now expanded to several tumor subtypes and in increasingly broader clinical contexts,including the adjuvant and neoadjuvant setting,with potentially curable patients and prolonged survival.The side effects related to these drugs include a wide spectrum of manifestations,with endocrinological adverse events being some of the most frequent.Pembrolizumab-induced type 1 diabetes mellitus is an infrequent but potentially serious and not clearly reversible side effect that possesses characteristic clinical features and has high morbidity and mortality,with a chronic impact on quality of life.The etiopathogenesis of this phenomenom needs to be further investigated and a collaborative effort through the involvement of oncologists and other medical specialists is necessary for the correct identification and management of patients at risk.展开更多
3背景三阴性乳腺癌（triple negative breast cancer，TNBC）即激素受体（hormone receptor，HR）阴性、人表皮生长因子受体2（humanepid ermal receptor2，HER2）阴性的亚型，占乳腺癌总发病率的20%。该亚型相较于激素受体阳性的乳腺...3背景三阴性乳腺癌（triple negative breast cancer，TNBC）即激素受体（hormone receptor，HR）阴性、人表皮生长因子受体2（humanepid ermal receptor2，HER2）阴性的亚型，占乳腺癌总发病率的20%。该亚型相较于激素受体阳性的乳腺癌亚型，通常具有更高的病理分级，易进展且侵袭性强，因为缺少治疗靶点导致治疗策略单一，只能选择毒副作用大的全身性化疗。目前研究表明程序性死亡受体1（programmed death receptor1，PD-1）单克隆抗体Pembrolizumab通过阻断PD-1/PD-L1信号通路，激发人体自身免疫系统对抗肿瘤细胞及避免肿瘤逃逸，对TNBC、黑色素瘤、胃癌、泌尿道上皮细胞癌及头颈部癌症等多种晚期进展性PD-L1阳性恶性肿瘤具有治疗潜力。展开更多
1文献来源Langer CJ,Gadgeel SM,Borghaei H,et al.Carboplatin and Pemetrexed with or without Pembrolizumab for advanced,non-squamous non-small-cell lung cancer：A randomised,phase 2 cohort of the open-label KEYNOTE-021 s...1文献来源Langer CJ,Gadgeel SM,Borghaei H,et al.Carboplatin and Pemetrexed with or without Pembrolizumab for advanced,non-squamous non-small-cell lung cancer：A randomised,phase 2 cohort of the open-label KEYNOTE-021 study[J].Lancet Oncol,2016,17（11）：1497-1508.2证据水平1b。3背景·在以往的临床试验中,单药PD-1抑制剂Pembrolizumab在晚期非小细胞肺癌（non-smallcell lung cancer,NSCLC）的治疗中已显示可喜的疗效。展开更多
BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-...BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells.The patient was started on pembrolizumab and,after 5 cycles,there was a more than 80 percent decrease in the size of the tumor mass.Further decrease was seen at the end of 10 cycles.The patient has been tolerating pembrolizumab well,with no limiting side-effects.Fourteen months after first coming into the hospital,he remains asymptomatic.CONCLUSION Pembrolizumab appears as a viable emerging treatment for PSC.展开更多
Background: Immune checkpoints inhibitors (ICIs) are widely used in various therapy of tumors. With the increasing usage of them, immune-related adverse events (irAEs) have been known and become common events, especia...Background: Immune checkpoints inhibitors (ICIs) are widely used in various therapy of tumors. With the increasing usage of them, immune-related adverse events (irAEs) have been known and become common events, especially in the dermatologic system. However, the rare and severe immune-related cutaneous adverse events (irCAEs) still lack enough knowledge. Case presentation: We described a rare case of Steven-Johnson syndrome (SJS) induced by pembrolizumab in an advanced squamous non-small cell lung cancer (NSCLC) patient. SJS is a rare irCAE that could happen at any time after immunotherapy while this case happened from the 3rd day. The patient had influence-like symptoms and several mucous lesions including oral, eye, and skin. With a gradually severer condition, a stoss therapy of intravenous immunoglobulin (IVIG) had a mild effect. It was a long process and failed to respond to usual dermatologic treatment. Conclusion: We share this case in order to enhance clinicians’ ability to early recognition and diagnosis in severe irCAEs. Early recognition and appropriate management are important to evade the termination of immunotherapy. Such severe irCAE should be paid more attention to in clinical medicine when using ICIs.展开更多
BACKGROUND Pembrolizumab is an anti-programmed death receptor 1(PD-1)that was shown to have a tolerable safety profile with 17%of grade 3-4 drug-related adverse events,notable response rate of 16%with median duration ...BACKGROUND Pembrolizumab is an anti-programmed death receptor 1(PD-1)that was shown to have a tolerable safety profile with 17%of grade 3-4 drug-related adverse events,notable response rate of 16%with median duration of response of 8 mo,and median overall survival of 8 mo.Severe mucositis is a very rare complication with only two cases of grade 4 mucositis reported,and both cases had good response to intravenous methylprednisolone and subsequent oral prednisone tapering.We report the first case of pembrolizumab-induced severe mucositis that was refractory to steroid treatment.CASE SUMMARY An 80-year-old woman with a past medical history of recurrent right cheek nodular melanoma status post resection and new right lung metastatic melanoma on immunotherapy presented with dysphagia and odynophagia for 2 mo.She initially received 2 doses of ipilimumab 1 year ago with good outcome,but treatment was discontinued after developing severe diarrhea and rash.Pembrolizumab was then initiated 4 mo after disease progression.Significant improvement was noted after 3 doses.However,after 6 cycles of pembrolizumab,patient developed odynophagia and malnutrition.Improvement of symptoms was noted after discontinuation of pembrolizumab and initiation of steroids.3 mo later,patient developed pharyngeal swelling with hoarseness and new oxygen requirement due to impending airway obstruction while being on prednisone tapering regimen,finally ended up with intubation and tracheostomy.Histologic analysis of left laryngeal and epiglottis tissue showed granulation tissue with acute on chronic inflammation,negative for malignancy and infection.Patient achieved marked improvement after 2 doses of infliximab of 5 mg/kg every 2 wk while continuing on prednisone tapering course.CONCLUSION We report the first case of pembrolizumab-induced grade 4 mucositis that had limited recovery with prolonged steroid course but had rapid response with addition of infliximab.The patient had recurrent mucositis symptoms whenever steroids was tapered but achieved complete response after receiving two doses of infliximab while continuing to be on tapering steroids.The success of infliximab in this patient with pembrolizumab-induced severe mucositis presents a potentially safe approach to reduce prolonged steroid course and accelerate recovery in managing this rare complication.展开更多
BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established...BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.展开更多
BACKGROUND For advanced lung squamous cell carcinoma,immune checkpoint inhibitors(ICIs)have been regarded as one of the optimal therapies.While immune-related adverse events(ir AEs)are common in ICI treatment,cutaneou...BACKGROUND For advanced lung squamous cell carcinoma,immune checkpoint inhibitors(ICIs)have been regarded as one of the optimal therapies.While immune-related adverse events(ir AEs)are common in ICI treatment,cutaneous toxicities are among the most common ir AEs.Most immune-related skin toxicity grades are low,and the prognosis is good.However,Stevens-Johnson syndrome(SJS)is a rare but extremely severe cutaneous adverse drug reaction with high mortality.CASE SUMMARY We report a rare case of SJS induced by pembrolizumab.The case involved a 68-year-old female who was diagnosed with advanced squamous cell carcinoma of the lung.SJS appeared after one cycle of immunotherapy combined with chemotherapy.After treatment with prednisone hormone symptoms,antiinfection,gamma globulin,and antipruritic agents,the skin toxicity of the patients gradually decreased and eventually disappeared.Although the antitumor treatment was stopped due to serious adverse reactions,the tumor of the patient remained stable for nearly half a year after one cycle of immune therapy combined with chemotherapy,which also corroborates the delayed effect of immunotherapy.CONCLUSION We believe our report can provide some references for the treatment of SJS and the treatment of immune-related adverse reactions.展开更多
基金financially supported by the Science and Technology Plan Project of Guangzhou (No. 202102010171)National Natural Science Foundation Cultivation Project of the Third Affiliated Hospital of Sun Yat-sen University (No. 2020GZRPYMS11)+2 种基金Natural Science Foundation of Guangdong Province (No. 2018A030313641)Natural Science Foundation of Guangdong Province (No. 2016A030313848)Science and Technology Plan Project of Guangzhou (No. 201704020175)。
文摘Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.
文摘Immune checkpoint inhibitors(and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab)initiated a revolution in the field of melanoma and have now expanded to several tumor subtypes and in increasingly broader clinical contexts,including the adjuvant and neoadjuvant setting,with potentially curable patients and prolonged survival.The side effects related to these drugs include a wide spectrum of manifestations,with endocrinological adverse events being some of the most frequent.Pembrolizumab-induced type 1 diabetes mellitus is an infrequent but potentially serious and not clearly reversible side effect that possesses characteristic clinical features and has high morbidity and mortality,with a chronic impact on quality of life.The etiopathogenesis of this phenomenom needs to be further investigated and a collaborative effort through the involvement of oncologists and other medical specialists is necessary for the correct identification and management of patients at risk.
文摘3背景三阴性乳腺癌（triple negative breast cancer，TNBC）即激素受体（hormone receptor，HR）阴性、人表皮生长因子受体2（humanepid ermal receptor2，HER2）阴性的亚型，占乳腺癌总发病率的20%。该亚型相较于激素受体阳性的乳腺癌亚型，通常具有更高的病理分级，易进展且侵袭性强，因为缺少治疗靶点导致治疗策略单一，只能选择毒副作用大的全身性化疗。目前研究表明程序性死亡受体1（programmed death receptor1，PD-1）单克隆抗体Pembrolizumab通过阻断PD-1/PD-L1信号通路，激发人体自身免疫系统对抗肿瘤细胞及避免肿瘤逃逸，对TNBC、黑色素瘤、胃癌、泌尿道上皮细胞癌及头颈部癌症等多种晚期进展性PD-L1阳性恶性肿瘤具有治疗潜力。
文摘1文献来源Langer CJ,Gadgeel SM,Borghaei H,et al.Carboplatin and Pemetrexed with or without Pembrolizumab for advanced,non-squamous non-small-cell lung cancer：A randomised,phase 2 cohort of the open-label KEYNOTE-021 study[J].Lancet Oncol,2016,17（11）：1497-1508.2证据水平1b。3背景·在以往的临床试验中,单药PD-1抑制剂Pembrolizumab在晚期非小细胞肺癌（non-smallcell lung cancer,NSCLC）的治疗中已显示可喜的疗效。
文摘BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells.The patient was started on pembrolizumab and,after 5 cycles,there was a more than 80 percent decrease in the size of the tumor mass.Further decrease was seen at the end of 10 cycles.The patient has been tolerating pembrolizumab well,with no limiting side-effects.Fourteen months after first coming into the hospital,he remains asymptomatic.CONCLUSION Pembrolizumab appears as a viable emerging treatment for PSC.
文摘Background: Immune checkpoints inhibitors (ICIs) are widely used in various therapy of tumors. With the increasing usage of them, immune-related adverse events (irAEs) have been known and become common events, especially in the dermatologic system. However, the rare and severe immune-related cutaneous adverse events (irCAEs) still lack enough knowledge. Case presentation: We described a rare case of Steven-Johnson syndrome (SJS) induced by pembrolizumab in an advanced squamous non-small cell lung cancer (NSCLC) patient. SJS is a rare irCAE that could happen at any time after immunotherapy while this case happened from the 3rd day. The patient had influence-like symptoms and several mucous lesions including oral, eye, and skin. With a gradually severer condition, a stoss therapy of intravenous immunoglobulin (IVIG) had a mild effect. It was a long process and failed to respond to usual dermatologic treatment. Conclusion: We share this case in order to enhance clinicians’ ability to early recognition and diagnosis in severe irCAEs. Early recognition and appropriate management are important to evade the termination of immunotherapy. Such severe irCAE should be paid more attention to in clinical medicine when using ICIs.
文摘BACKGROUND Pembrolizumab is an anti-programmed death receptor 1(PD-1)that was shown to have a tolerable safety profile with 17%of grade 3-4 drug-related adverse events,notable response rate of 16%with median duration of response of 8 mo,and median overall survival of 8 mo.Severe mucositis is a very rare complication with only two cases of grade 4 mucositis reported,and both cases had good response to intravenous methylprednisolone and subsequent oral prednisone tapering.We report the first case of pembrolizumab-induced severe mucositis that was refractory to steroid treatment.CASE SUMMARY An 80-year-old woman with a past medical history of recurrent right cheek nodular melanoma status post resection and new right lung metastatic melanoma on immunotherapy presented with dysphagia and odynophagia for 2 mo.She initially received 2 doses of ipilimumab 1 year ago with good outcome,but treatment was discontinued after developing severe diarrhea and rash.Pembrolizumab was then initiated 4 mo after disease progression.Significant improvement was noted after 3 doses.However,after 6 cycles of pembrolizumab,patient developed odynophagia and malnutrition.Improvement of symptoms was noted after discontinuation of pembrolizumab and initiation of steroids.3 mo later,patient developed pharyngeal swelling with hoarseness and new oxygen requirement due to impending airway obstruction while being on prednisone tapering regimen,finally ended up with intubation and tracheostomy.Histologic analysis of left laryngeal and epiglottis tissue showed granulation tissue with acute on chronic inflammation,negative for malignancy and infection.Patient achieved marked improvement after 2 doses of infliximab of 5 mg/kg every 2 wk while continuing on prednisone tapering course.CONCLUSION We report the first case of pembrolizumab-induced grade 4 mucositis that had limited recovery with prolonged steroid course but had rapid response with addition of infliximab.The patient had recurrent mucositis symptoms whenever steroids was tapered but achieved complete response after receiving two doses of infliximab while continuing to be on tapering steroids.The success of infliximab in this patient with pembrolizumab-induced severe mucositis presents a potentially safe approach to reduce prolonged steroid course and accelerate recovery in managing this rare complication.
文摘BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.
文摘BACKGROUND For advanced lung squamous cell carcinoma,immune checkpoint inhibitors(ICIs)have been regarded as one of the optimal therapies.While immune-related adverse events(ir AEs)are common in ICI treatment,cutaneous toxicities are among the most common ir AEs.Most immune-related skin toxicity grades are low,and the prognosis is good.However,Stevens-Johnson syndrome(SJS)is a rare but extremely severe cutaneous adverse drug reaction with high mortality.CASE SUMMARY We report a rare case of SJS induced by pembrolizumab.The case involved a 68-year-old female who was diagnosed with advanced squamous cell carcinoma of the lung.SJS appeared after one cycle of immunotherapy combined with chemotherapy.After treatment with prednisone hormone symptoms,antiinfection,gamma globulin,and antipruritic agents,the skin toxicity of the patients gradually decreased and eventually disappeared.Although the antitumor treatment was stopped due to serious adverse reactions,the tumor of the patient remained stable for nearly half a year after one cycle of immune therapy combined with chemotherapy,which also corroborates the delayed effect of immunotherapy.CONCLUSION We believe our report can provide some references for the treatment of SJS and the treatment of immune-related adverse reactions.
