Predicting hyperprogressive disease in patients with advanced hepatocellular carcinoma treated with anti-programmed cell death 1 therapy.
Zhang Lu,Wu Lingeng,Chen Qiuying,Zhang Bin,Liu Jing,Liu Shuyi,Mo Xiaokai,Li Minmin,Chen Zhuozhi,Chen Luyan,You Jingjing,Jin Zhe,Chen Xudong,Zhou Zejian,Zhang Shuixing
Background:Hyperprogressive disease (HPD) is a new progressive pattern in patients with advanced hepatocellular carcinoma (HCC) treated with programmed cell death 1 (PD-1) inhibitors. We aimed to investigate risk factors associated with HPD in advanced HCC patients undergoing anti-PD-1 therapy. Methods:A total of 69 patients treated with anti-PD-1 therapy between March 2017 and January 2020 were included. HPD was determined according to the time to treatment failure, tumour growth rate, and tumour growth rate ratio. Univariate and multivariate analyses were performed to identify clinical variables significantly associated with HPD. A risk model was constructed based on clinical variables with prognostic significance for HPD. Findings:Overall, 10 (14·49%) had HPD. Haemoglobin level, portal vein tumour thrombus, and Child-Pugh score were significantly associated with HPD. The risk model had an area under the curve of 0·931 (95% confidence interval, 0·844-1·000). Patients with HPD had a significantly shorter overall survival (OS) than that of the patients with non-HPD ( < 0·001). However, there was no significant difference in OS between PD (progressive disease) patients with and without HPD ( = 0·05). Interpretation:We identified three clinical variables as risk factors for HPD, providing an opportunity to aid the pre-treatment evaluation of the risk of HPD in patients treated with immunotherapy. Funding:This study was funded by the National Natural Science Foundation of China (81571664, 81871323, and 81801665); National Natural Science Foundation of Guangdong Province (2018B030311024); Scientific Research General Project of Guangzhou Science Technology and Innovation Commission (201707010,328); and China Postdoctoral Science Foundation (2016M600145).
Hyperprogressive disease in hepatocellular carcinoma with immune checkpoint inhibitor use: a case series.
Wong Daniel Jiahao,Lee Joycelyn,Choo Su Pin,Thng Choon Hua,Hennedige Tiffany
Immune checkpoint inhibitors (ICIs) have demonstrated promising results in a variety of advanced cancer types. The phenomenon of hyperprogressive disease (HPD) has only been documented in recent years, however, there have been no reports of HPD in hepatocellular carcinoma. We present a case series of six patients with advanced hepatocellular carcinoma treated with ICIs who demonstrated rapid radiological progression, this was confirmed by comparing tumor growth rates before and during treatment with HPD defined as tumor growth rate ≥2. Although ICIs have demonstrated profound efficacy in advanced cancer, they might also be responsible for HPD in a small subset of patients. The ability to predict treatment response to ICI is thus of importance in protecting patients from the deleterious effects of HPD.
Nivolumab induced hyperprogressive disease in advanced esophageal squamous cell carcinoma.
Sun Dantong,Liu Dong,Liu Qiaoling,Hou Helei
Cancer biology & therapy
Immune checkpoint inhibitors have demonstrated promising efficacy and tolerable safety for advanced malignancies. However, a proportion of patients who had received immunotherapy may experience hyperprogressive disease and a resultant poor prognosis. Here, we report a patient with advanced esophageal squamous carcinoma who developed hyperprogressive disease shortly after immunotherapy. This patient received nivolumab after multiple lines of treatment, including chemotherapy, radiotherapy, and antiangiogenic therapy. Through the comprehensive analysis of NGS results, we concluded that the PI3K/AKT signaling pathway might be associated with hyperprogressive disease after immunotherapy. Additionally, potential mechanisms underlying hyperprogressive disease after immunotherapy reported in other malignant tumors were also summarized.
Hyperprogressive disease in early-phase immunotherapy trials: Clinical predictors and association with immune-related toxicities.
Kanjanapan Yada,Day Daphne,Wang Lisa,Al-Sawaihey Hamad,Abbas Engy,Namini Amirali,Siu Lillian L,Hansen Aaron,Razak Albiruni Abdul,Spreafico Anna,Leighl Natasha,Joshua Anthony M,Butler Marcus O,Hogg David,Chappell Mary Anne,Soultani Ludmilla,Chow Kayla,Boujos Samantha,Bedard Philippe L
BACKGROUND:A subset of patients treated with immune checkpoint inhibitors experience an accelerated tumor growth rate (TGR) in comparison with pretreatment kinetics; this is known as hyperprogression. This study assessed the relation between hyperprogressive disease (HPD) and treatment-related toxicity and clinical factors. METHODS:This study reviewed patients with solid tumors who were enrolled in early-phase immunotherapy trials at Princess Margaret Cancer Centre between August 2012 and September 2016 and had computed tomography scans in the pre-immunotherapy (reference) and on-immunotherapy (experimental) periods. HPD was defined as progression according to Response Evaluation Criteria in Solid Tumors 1.1 at the first on-treatment scan and a ≥2-fold increase in TGR between the reference and experimental periods. Treatment-related toxicities requiring systemic therapy, drug delays, or discontinuation were considered clinically significant adverse events (CSAEs). RESULTS:Of 352 patients, 182 were eligible for analysis. The median age was 60 years, and 54% were male. The Eastern Cooperative Oncology Group performance status was 0 (32%) or 1 (68%). The Royal Marsden Hospital (RMH) prognostic score was 0/1 in 59%. Single-agent immunotherapy was given to 80% of the patients. Most patients (89%) received anti-programmed death (ligand) 1 antibodies alone or in combination with other therapies. HPD occurred in 12 of 182 patients (7%). A higher proportion of females was seen among HPD patients (P = .01), but no association with age, performance status, tumor type, RMH prognostic score, combination immunotherapy, or CSAEs was found. The 1-year overall survival rate was 28% for HPD patients and 53% for non-HPD patients (hazard ratio, 1.7; 95% confidence interval, 0.9-3.3; P = .11). CONCLUSIONS:HPD was observed in 7% of patients with solid tumors treated with immunotherapy. HPD was not associated with CSAEs, age, tumor type, or the type of immunotherapy but was more common in females.