Treatment-related adverse events, including fatal toxicities, in patients with solid tumours receiving neoadjuvant and adjuvant immune checkpoint blockade: a systematic review and meta-analysis of randomised controlled trials

Fujiwara, Yu; Horita, Nobuyuki; Adib, Elio; Zhou, Susu; Nassar, Amin H; Asad, Zain UL Abideen; Cortellini, Alessio; Naqash, Abdul Rafeh

doi:10.1016/s1470-2045(23)00524-7

Cited by 15 publications

(2 citation statements)

References 51 publications

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“…We also saw in our work that there is significant heterogeneity in the incidence of G3-5 toxicity even when we focused on one regimen (eg Lenvatinib and Pembrolizumab). This is also apparent in other published works which focus on PD-1/PD-L1 inhibitors alone, where significant heterogeneity was also observed ( 28 , 29 ). Our and others work are indicative that heterogeneity observed in toxicity meta-analysis may occur even when ICI/TKI combinations and diseases are homogenous.…”

Section: Discussionsupporting

confidence: 65%

Toxicity of immune checkpoint inhibitors and tyrosine kinase inhibitor combinations in solid tumours: a systematic review and meta-analysis

O’Reilly,

O’Leary,

Reilly

et al. 2024

Front. Oncol.

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The combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) can be associated with significant toxicity. We performed a systematic review and meta-analysis of the toxicity of combination treatment of ICIs with TKIs (ICI + TKI) in clinical trials with solid organ malignancies. Our primary endpoint explored the incidence of grade 3 - 5 (G3-5) treatment-related toxicity and our secondary endpoints included the incidence of toxicity by treatment type, disease type and studies with run-in strategies. A total of 9750 abstracts were identified, of which 72 eligible studies were included. The most common disease types were non-small cell lung cancer (n=8, 11.1%), renal cell carcinoma (n=10, 13.8%) and hepatobiliary cancers (n=10, 13.8%). The overall incidence of G3-5 toxicity was 56% (95% CI = 50% – 61%). The most common TKIs combined with ICIs in this analysis were multi-targeted TKIs (n = 52, 72%), VEGF specific (n = 9, 12.5%), or oncogene-targeting TKIs (EGFR, ALK, BRAF, MEK) (n =11, 15.3%). Oncogene-targeted TKIs were associated a higher incidence of rashes and immune related adverse events (irAEs) and lower incidence of hypertension. In studies which used a TKI ‘run-in’ to mitigate toxicity, the pooled estimate of G3-5 toxicity was 71% (95% CI 57-81%). Almost half of studies (48%) omitted the incidence of G3-5 irAEs. Our work suggests that the majority of patients who receive ICI-TKI combinations will experience high grade toxicity (G3-G5) and that toxicity may be specific to TKI partner (Oncogene targeted TKIs: Rash, irAEs; VEGF/Multitargeted: Hypertension). These data did not suggest that a TKI ‘run-in’ was associated with a lower incidence of G3-5 toxicity. Reporting of irAEs was inconsistent supporting the need for harmonisation of adverse event reporting to include onset, duration and treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022367416.

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Section: Discussionsupporting

confidence: 65%

Toxicity of immune checkpoint inhibitors and tyrosine kinase inhibitor combinations in solid tumours: a systematic review and meta-analysis

O’Reilly,

O’Leary,

Reilly

et al. 2024

Front. Oncol.

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“…Although immunotherapy has brought us huge benefits in clinical treatment, the safety issues it brings have also attracted our attention. We need to detect related adverse reactions early and make corresponding treatments ( 33 ). Although hilar and mediastinal lymph node fibrosis and thoracic adhesions after neoadjuvant therapy may affect operation, relevant studies show that the surgical rate of patients after neoadjuvant immunotherapy is 81–95% while the R0 resection rate is as high as 100%, and the complications of surgery after neoadjuvant immunotherapy for early-stage lung cancer do not appear to be significantly increased ( 26 , 29 , 30 , 34 ).…”

Section: International Mdt (Imdt) Discussionmentioning

confidence: 99%

Single-port video-assisted thoracoscopic sleeve lobectomy after neoadjuvant immunochemotherapy: a case report

Chen,

Zhang,

Rossi

et al. 2024

Transl Lung Cancer Res

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Background The morbidity and mortality of lung cancer have always ranked first among malignant tumors (MTs). Previous studies have shown that neoadjuvant chemotherapy can improve the 5-year survival rate of patients with non-small cell lung cancer (NSCLC), but the benefit is limited. Studies have proven that neoadjuvant immunotherapy combined with chemotherapy has unique advantages in prolonging patient survival, reducing distant recurrence, and inducing antitumor immunity. However, its impact remains to be more comprehensively investigated. Case Description A 59-year-old male who was admitted to the hospital with a primary complaint of repeated cough and expectoration for 6 months. Preoperative assessment showed right upper lung squamous cell carcinoma with multiple hilar and mediastinal lymph node metastasis, and the clinical stage was cT2aN2M0 stage (IIIA). After three cycles of pembrolizumab + carboplatin + paclitaxel therapy were administered, the reexamination of the tumor was evaluated as partial response (PR), and a sleeve lobectomy of the right upper lung was performed under single-port thoracoscopic surgery. The operation proceeded smoothly without conversion to thoracotomy, and R0 resection was successfully achieved. Postoperative pathological stage was ypT1bN0M0 stage IA, and postoperative pathological remission was evaluated as major pathological response (MPR). After the operation, three cycles of immunotherapy combined with chemotherapy were completed, which was followed by maintenance therapy with pembrolizumab monotherapy for 1 year, and no signs of tumor recurrence and metastasis have been found in follow-up thus far. Conclusions Through this case, we believe that for locally advanced NSCLC sleeve lobectomy after neoadjuvant therapy may be a safe and feasible treatment option, can avoid pneumonectomy, protect the lung function of patients, and still ensure the R0 resection rate. Moreover, it may does not significantly increase the difficulty of surgical operation or reduce safety. However, further research is needed to confirm our conclusion. And then, neoadjuvant therapy in the perioperative period may induce a series of side effects or adverse reactions, and thus greater attention should be paid to its timely management.

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Die neoadjuvante Immunchemotherapie des nichtkleinzelligen Lungenkarzinoms: Was Thoraxchirurginnen und -chirurgen wissen müssen

Dörr-Jerat,

Möller,

Schütte

et al. 2024

Z Herz- Thorax- Gefäßchir

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Treatment-related adverse events, including fatal toxicities, in patients with solid tumours receiving neoadjuvant and adjuvant immune checkpoint blockade: a systematic review and meta-analysis of randomised controlled trials

Cited by 15 publications

References 51 publications

Toxicity of immune checkpoint inhibitors and tyrosine kinase inhibitor combinations in solid tumours: a systematic review and meta-analysis

Toxicity of immune checkpoint inhibitors and tyrosine kinase inhibitor combinations in solid tumours: a systematic review and meta-analysis

Single-port video-assisted thoracoscopic sleeve lobectomy after neoadjuvant immunochemotherapy: a case report

Die neoadjuvante Immunchemotherapie des nichtkleinzelligen Lungenkarzinoms: Was Thoraxchirurginnen und -chirurgen wissen müssen

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