Predictors of Response,Progression-Free Survival,and Overall Survival in Patients With Lung Cancer Treated With Immune Checkpoint Inhibitors

Monoclonal antibodies that target immune checkpoint proteins, so-called immune checkpoint inhibitors, prevent tumor evasion of the immune system and are often effective in the treatment of lung cancer. Studies have revealed improved objective response rates, progression-free survival, and overall survival with immune checkpoint inhibitors when used in both first and subsequent-line settings. Unfortunately, only a subset of unselected patients with lung cancer responds to these therapies. An important area of ongoing research is to identify biomarkers that can predict which patients are most likely to derive clinical benefit. This review will discuss established and emerging biomarkers from some of the clinical trials that have demonstrated the efficacy of immune checkpoint inhibitors for the treatment of both NSCLC and SCLC.     

Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Previously Untreated Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and safety of immune checkpoint inhibitors plus platinum–etoposide (ICIs+EP) with platinum–irinotecan (IP) or directly compared different ICIs+EP for previously untreated ES-SCLC. This study used a Bayesian approach for network meta-analysis to compare efficacy and safety between ICIs+EP and IP and between each pair of three ICIs+EP. The six treatment arms were: pembrolizumab plus platinum–etoposide (Pem+EP), durvalumab plus platinum–etoposide (Dur+EP), atezolizumab plus platinum–etoposide (Atz+EP), platinum–amrubicin (AP), IP, and platinum–etoposide (EP). No significant differences in overall survival were observed between ICIs+EP and IP and between each pair of three ICIs+EP. The incidence of ≥grade 3 adverse events (G3-AEs) was significantly higher in ICIs+EP than IP, whereas no significant difference was found in G3-AEs between each pair of three ICIs+EP. The incidence of ≥grade 3 neutropenia and thrombocytopenia was significantly higher in ICIs+EP than IP, whereas the incidence of ≥grade 3 diarrhea was significantly lower in ICIs+EP than IP. These findings will help clinicians better select treatment strategies for ES-SCLC.     

Developing a Predictive Model for Clinical Outcomes of Advanced Non-Small Cell Lung Cancer Patients Treated With Nivolumab

Introduction

Despite significant improvement of clinical outcomes of advanced non–small-cell lung cancer (NSCLC) patients treated with immunotherapy, our knowledge of optimal biomarkers is still limited.

肿瘤突变负荷对PD-1/PD-L1抑制剂治疗非小细胞肺癌临床疗效预测的Meta分析

目的 探讨肿瘤突变负荷(TMB)与PD-1/PD-L1抑制剂治疗非小细胞肺癌(NSCLC)疗效的相关性.方法 系统检索PubMed、Embase和Cochrane Library、CNKI、中国生物医学数据库(Chinese Biomedical Literature Database,CBM)和万方数据库,检索日期截...     

Wait Times and Survival in Lung Cancer Patients across the Province of Quebec,Canada

Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017. Patients were followed for 3 years. Wait times for diagnosis and treatment were collected, and survival analysis using a Cox regression model was conducted. We included 1309 patients, of whom 39% had stage IV non-small cell lung cancer (NSCLC). Median wait times were, in general, significantly shorter in patients with stage III–IV NSCLC or SCLC. Surgery was associated with delays compared to other types of treatments. Median survival was 12.9 (11.1–15.7) months. The multivariate survival model included age, female sex, performance status, histology and stage, treatment, and the time interval between diagnosis and treatment. Longer wait times had a slightly protective to neutral effect on survival, but this was not significant in the stage I–II NSCLC subgroup. Wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced NSCLC and SCLC might indicate a tendency for clinicians to act quicker on sicker patients. This study did not demonstrate the detrimental effect of longer wait times on survival.     

KRAS Mutation as a Biomarker for Survival in Patients with Non-Small Cell Lung Cancer,A Meta-Analysis of 12 Randomized Trials

Background: Because there is no clear consensus for the prognostic implication of KRAS mutations in patientswith non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to drawa more accurate conclusion. Materials and Methods: A systematic computer search of articles from inception toMay 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articlesand extraction of data were independently performed by two authors. Results: Our analysis was based onthe endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS)comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations.In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) andPFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC.According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS andPFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However,the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treatedwith chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643).Conclusions: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLCbut not for those treated with chemotherapies integrating cetuximab.     

Long-Term Survival of Patients With Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitor Monotherapy in Real-World Settings

BackgroundImmune checkpoint inhibitor (ICI) monotherapy is more effective than cytotoxic chemotherapy in improving overall survival (OS) among patients with advanced-stage non-small cell lung cancer (NSCLC). Recently, chemotherapy combined with ICI has been found to yield good outcomes. However, ICI monotherapy is still considered an important treatment option. Data on long-term progression-free survival (PFS) and OS in real-world settings are limited.Patients and MethodsThis was a multicenter retrospective observational study. A total of 435 consecutive patients histologically diagnosed with advanced, metastatic, or recurrent NSCLC treated with ICI monotherapy were enrolled in this study from December 2015 to December 2018. Clinical data were collected from electronic medical records and pharmacy databases.ResultsThe PFS and OS of the patients were 3.4 and 13.0 months, respectively. The objective response and disease control rates were 22.8% and 54.9%, respectively, and the 4-year survival rate was 17.9%. Multivariate analyses revealed that elder patients (>70 years), good Eastern Cooperative Oncology Group Performance Status (ECOG PS) score, programmed death-ligand 1 tumor proportion score (PD-L1 TPS) of ≥ 50%, absence of bone metastasis, and presence of immune-related skin toxicity, which is an immune-related adverse event, were correlated with good PFS. Moreover, good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good OS.ConclusionsThe 4-year survival rate was 17.9%. Good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good PFS and OS.     

Clinical Application of Recombinant Human Endostatin in Postoperative Early Complementary Therapy on Patients with Non-small Cell Lung Cancer in Chinese Mainland

Objective: To explore the clinical application of recombinant human endostatin (Endostar) in the treatmentof patients with non-small cell lung cancer (NSCLC) in Chinese mainland. Materials and Methods: A total of75 patients diagnosed as NSCLC were randomly divided into control group (37 cases) and treatment group(38 cases). Control group was treated with postoperative complementary chemotherapy containing two-agentplatinum protocol on postoperative d21, 3 weeks as a cycle, for totally 4~6 cycles. On this basis, treatment groupwas added with Endostar 7.5 mg/m2 on postoperative d8~9, 3~4 h/time, qd, 14 weeks as a cycle, for totally 4cycles. The interval between every two cycles was 7 d. The 5-year progression-free survival (PFS), 5-year survivaltime and complications in both groups were observed. Results: Compared with control group, the average PFSincreased evidently in treatment group by 9.8 months (41.6 months vs. 31.8 months), and there was significantdifference (P<0.05). And the median PFS was 42.5 months in treatment group, obviously longer than that incontrol group (33.7 months) by 8.8 months (P<0.05). Additionally, the 5-year overall survival rate (OS), averagesurvival time and median survival time (MST) were 47.4%, 50.1 months and 59.3 months in treatment group,significantly higher than the 29.7%, 42.1 months and 43.5 months in control group (P<0.05). Only 1 patientshowed poor healing of surgical wound in treatment group, but no surgery-associated complication was foundin control group. Moreover, the postoperative complementary therapy-connected complication rates were63.2% (24/38) and 59.5% (22/37) in treatment group and control group respectively, but there was no significantdifference (P>0.05). Conclusions: The application of Endostar combined with sensitive platinum-containedchemotherapeutic agents in the postoperative complementary chemotherapy can be widely used in clinic becauseit can significantly prolong the long-term survival time of patients with NSCLC.     

Meta-Analysis of Neoadjuvant Immunotherapy for Patients with Resectable Non-Small Cell Lung Cancer

Purpose: Immunotherapy has created a paradigm shift in the treatment of metastatic non-small cell lung cancer (NSCLC), overcoming the therapeutic plateau previously achieved by systemic chemotherapy. There is growing interest in the utility of immunotherapy for patients with resectable NSCLC in the neoadjuvant setting. The present systematic review and meta-analysis aim to provide an overview of the existing evidence, with a focus on pathological and radiological response, perioperative clinical outcomes, and long-term survival. Methods: A systematic review was conducted using electronic databases from their dates of inception to August 2021. Pooled data on pathological response, radiological response, and perioperative outcomes were meta-analyzed where possible. Results: Eighteen publications from sixteen studies were identified, involving 548 enrolled patients who underwent neoadjuvant immunotherapy, of whom 507 underwent surgery. Pathologically, 52% achieved a major pathological response, 24% a complete pathological response, and 20% reported a complete pathological response of both the primary lesion as well as the sampled lymph nodes. Radiologically, 84% of patients had stable disease or partial response. Mortality within 30 days was 0.6%, and morbidities were reported according to grade and frequency. Conclusion: The present meta-analysis demonstrated that neoadjuvant immunotherapy was feasible and safe based on perioperative clinical data and completion rates of surgery within their intended timeframe. The pathological response after neoadjuvant immunotherapy was superior to historical data for patients who were treated with neoadjuvant chemotherapy alone, whilst surgical and treatment-related adverse events were comparable. The limitations of the study included the heterogenous treatment regimens, lack of long-term follow-up, variations in the reporting of potential prognostic factors, and potential publication bias.     

Outcomes With First-line PD-1/PD-L1 Inhibition in Advanced Urothelial Cancer: A Single Institution Experience

BackgroundFirst-line PD-inhibition in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer represents a novel clinical setting, with uncertainty concerning second-line outcomes. Specifying second-line treatment and outcomes will provide guidance in this new sequence. We performed a retrospective chart review to document the outcomes of these patients treated at our institution.Patients and MethodsOur cohort consisted of 43 patients with advanced urothelial cancer receiving first-line checkpoint inhibition. Baseline factors, programmed death-ligand 1 (PD-L1) status, treatments, and outcomes during and beyond the first line were obtained. Response was scored using Response Evaluation Criteria in Solid Tumors, version 1.1 criteria. Log rank tests were used to compare outcomes in prognostic subgroups, and outcome associations with PD-L1 status were analyzed with Fisher exact tests.ResultsA total of 43 patients received first-line atezolizumab or pembrolizumab from June 2014 until June 2018. The median age was 76.8 years, and the population was 74% male, with 60% having visceral metastases. Reasons for cisplatin ineligibility were Eastern Cooperative Oncology Group performance status 2%, 30%; renal insufficiency, 44%, and both, 21%. First-line objective response rate (ORR) was 30%, and complete response was 14%. The median overall survival was 11.7 months. Of 29 patients progressing, 17 received second-line treatment (most commonly, gemcitabine/carboplatin [10 patients]). The second-line response rate was 33%, and the ORR was 11%. The second-line median overall survival was 6.2 months. No association was found between PD-L1 status and outcomes.ConclusionOutcomes with first-line immunotherapy are consistent with historical outcomes. The ORR after first-line checkpoint inhibition falls short of historical comparators; however, the response rate compares favorably to those of chemotherapies used in previous second-line regimens. The older age and poorer performance status may have contributed to second-line outcomes.     

Association of PD-L1 expression status with the efficacy of PD-1/PD-L1 inhibitors and overall survival in solid tumours: A systematic review and meta-analysis

Whether PD-L1-positive patients derive more overall survival benefit from PD-1/PD-L1 inhibitors in the treatment of advanced solid tumours is unclear. We systematically searched the PubMed, Cochrane library and EMBASE databases from January 1, 1966 to March 1, 2019, to identify randomised controlled trials of PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, atezolizumab, durvalumab and avelumab) that had available hazard ratios (HRs) for death according to PD-L1 status. A random-effects model was used to calculate the pooled overall survival (OS) HR and 95% CI among PD-L1-positive and PD-L1-negative patients. An interaction test was performed to evaluate the heterogeneity between the two estimates. A total of 24 randomised trials, involving 12,966 participants, fulfilled the inclusion criteria. An OS benefit of PD-1/PD-L1 inhibitors was found in both PD-L1-positive patients (HR, 0.65; 95% CI, 0.60–0.70) and PD-L1-negative patients (HR, 0.82; 95% CI, 0.74–0.91) even at the minimum cut-off value of 1%. Significant differences in the efficacy of PD-1/PD-L1 inhibitors between PD-L1-positive and PD-L1-negative patients were noted at different cut-off values. Moreover, there was a positive dose–response relationship between PD-L1 positivity and OS benefit (HR for 1%, 0.58, [0.50, 0.67]; 5%, 0.52 [0.43, 0.64]; 10%, 0.50 [0.40, 0.63]). Subgroup analyses showed that these results were generally consistent, regardless of study design, line of treatment, treatment type, tumour type, PD-L1 staining cell type and median follow-up time. We demonstrated that PD-1/PD-L1 inhibitors significantly improved OS in both PD-L1 positive and PD-L1 negative patients compared to controls, but the magnitude of benefit was clinically PD-L1-dependent.     

Hypofractionated Concomitant Chemoradiation in Inoperable Locally Advanced Non-small Cell Lung Cancer: A Report on 100 Patients and a Systematic Review

Aims

Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation.

Lung Cancer in Women,a Different Disease: Survival Differences by Sex in Turkey

Purpose: In this study, we aimed to evaluate the effects of sex-based non-small cell lung cancer (NSCLC)varieties on survival rates. Materials and Methods: A retrospective study was performed in patients with NSCLCwho were diagnosed by histological methods between the years 2000 and 2010. A chi-square test was used tocompare variables. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Of the 844patients, 117 (13.9%) were women and 727 (86.1%) were men. Adenocarcinoma was more common in womenthan in men (p<0.0001). There were more women non-smokers than men (p<0.0001). There was no statisticallysignificant difference in ECOG PS, weight loss>10%, stage, LDH, albumin and treatment between women andmen. Women younger than 65 years (17.0 vs 12.0 months; p=0.03), who had adenocarcinoma histology (15.0 vs10.0 months; p=0.006) and who had a hemoglobin level ≥12g/dL (18.0 vs 12.0 months; p=0.01) were found to havea better median OS rate than men. Median OS rates were found to be 13.0 months in females and 12.0 monthsin males (p=0.14). Among metastatic patients, the median OS was 11.0 months in females and 8.0 months inmales (p=0.005). Among stage IIIB and stage IV patients who had first line platinum-based chemotherapy, themedian OS was 17.0 months in women and 11.0 months in men (p=0.002). The response rate of chemotherapywas higher in women than in men (p=0.03). Conclusions: In our study, we found that survival duration is longerand chemotherapy response is better in women with NSCLC who do not have anemia or comorbidities and whoare mostly non-smokers with adenocarcinomas. Further studies regarding the causes of these differences mayprovide clarity on this subject.     

Clinical Outcomes With Pembrolizumab-Based Therapies in Recurrent/Refractory NSCLC After Chemoradiation and Consolidative Durvalumab

BackgroundOften, patients with NSCLC experience recurrent/refractory (R/R) disease within 2 years of chemoradiation (CRT) and consolidative durvalumab. Despite prior immune checkpoint inhibitor exposure, immunotherapy with or without chemotherapy is typically initiated if a driver-oncogene is absent. However, there remains a paucity of data regarding the efficacy of immunotherapy in this patient population. Here, we present survival outcomes associated with pembrolizumab for R/R NSCLC.Materials and MethodsWe retrospectively assessed adults with NSCLC who received pembrolizumab for R/R disease between January 2016 to January 2023. Primary objective was to estimate OS and PFS in this cohort compared to historical outcomes. Secondary objective was to compare OS and PFS among subgroups.ResultsFifty patients were evaluated. Median follow-up time was 11.3 months (2.9-38.2). OS was 10.6 months (95% CI, 8.8-19.2); 1-year OS rate 49% (95% CI, 36 - 67%). PFS was 6.1 months (95% CI, 4.7-9.0); 1-year PFS rate 25% (95% CI, 15%-42%). Current smokers had significantly better median OS/PFS as compared to former smokers (NA vs. 10.5 and 9.9 vs. 6.0 months, respectively). The addition of chemotherapy demonstrated an OS benefit (median OS 12.9 vs. 6.0 months) but was not statistically significant.ConclusionPatients with R/R NSCLC represent a distinct cohort with inferior survival outcomes when compared to those with de novo stage IV disease treated with pembrolizumab-based regimens. Based on our findings, we recommend oncologists exercise caution when considering checkpoint inhibitor monotherapy in the front-line setting for R/R NSCLC, regardless of PD-L1 expression.     

肺癌神经内分泌分化与术后生存关系探讨(英文)

目的探讨非小细胞肺癌神经内分泌(NSCLC-NE)分化与患者手术后生存关系。方法收集1997年4月～1999年4月98例肺癌手术切除病理标本,采用免疫组化标记特异性烯醇化酶(NSE)及突触素(SY),并按强弱区分为“+、++、+++”。对同一手术病例标本采用电镜观察特异性 NE 颗粒。术后病例随访36例,最长60月。采用Cox 多因素风险模型分析 NSCLC-NE 分化与患者术后生存的关系。结果 91例为非小细胞肺癌。非小细胞肺癌 NE 阳性表达率为63.7%(58/91),其中 NSE 阳性表达54例(59.3%),SY 阳性表达22例(24.1%),电镜观察 NE 特异性颗粒30例(33.0%)。结合免疫组化和电镜观察 NSCLC-NE 分化44例(48.4%)。Cox 模型多因素分析结果表明 NSCLC-NE 分化者术后生存时间明显缩短(P=0.048)。术后生存与肺癌细胞分化程度(P=0.006)、病理分期(P=0.001)、NE 表达强弱(P=0.054)有密切关系。结论 NSCLC-NE 分化与肿瘤细胞分化和患者术后生存有关。采用 NE 标志特标记肿瘤,并观察其强弱改变,对术后评估具有较重要的参考意义,可作为临床判断患者预后指标之一。     

肺癌神经内分泌分化与术后生存关系探讨

目的探讨非小细胞肺癌神经内分泌(NSCLC-NE)分化与患者手术后生存关系。方法收集1997年4月-1999年4月98例肺癌手术切除病理标本,采用免疫组化标记特异性烯醇化酶(NSE)及突触素(SY),并按强弱区分为“ 、 、 ”。对同一手术病例标本采用电镜观察特异性NE颗粒。术后病例随访36例,最长60月。采用Cox多因素风险模型分析NSCLC-NE分化与患者术后生存的关系。结果91例为非小细胞肺癌。非小细胞肺癌NE阳性表达率为63.7%(58/91),其中NSE阳性表达54例(59.3%),SY阳性表达22例(24.1%),电镜观察NE特异性颗粒30例(33.0%)。结合免疫组化和电镜观察NSCLC-NE分化44例(48.4%)。Cox模型多因素分析结果表明NSCLC-NE分化者术后生存时间明显缩短(P=0.048)。术后生存与肺癌细胞分化程度(P=0.006)、病理分期(P=0.001)、NE表达强弱(P=0.054)有密切关系。结论NSCLC-NE分化与肿瘤细胞分化和患者术后生存有关。采用NE标志特标记肿瘤,并观察其强弱改变,对术后评估具有较重要的参考意义,可作为临床判断患者预后指标之一。     

Assessment of Immune-Related Interstitial Lung Disease in Patients With NSCLC Treated with Immune Checkpoint Inhibitors: A Multicenter Prospective Study

IntroductionProgrammed cell death protein 1 immune checkpoint inhibitors (ICIs) have been reported to improve the survival of patients with NSCLC. On the expansion of clinical administration for a variety of cancers, immune-related adverse events have been typically recognized to be associated with ICIs, therefore, necessitating the monitoring and management of these patients. Among immune-related adverse events, immune-related interstitial lung disease (ir-ILD) is a serious complication that interrupts treatment and can occasionally be fatal. However, no prospective studies have investigated the incidence of ir-ILD and associated risk factors for its development in the clinical setting.MethodsThis is a prospective cohort study consisting of patients with NSCLC treated with ICIs. Baseline characteristics, including laboratory data, pulmonary function tests, daily symptoms of dyspnea defined by the modified Medical Research Council, and antitumor response were assessed.ResultsAmong the 138 patients with NSCLC who received anti–programmed cell death protein 1 monotherapy, 20 patients (14.5%) had ir-ILD within median 51.5 days (interquartile range: 29–147). This was approximately three times higher than those in clinical trials. A total of 11 patients (55.0%), including all eight patients with high-grade ir-ILD (≥grade 3), developed ir-ILD within 60 days. Impaired spirometry, decreased forced vital capacity and forced expiratory volume in 1 second, and daily symptoms of dyspnea measured using the modified Medical Research Council scale were identified as risk factors for ir-ILD development. In addition, combination assessment of forced vital capacity and forced expiratory volume in 1 second successfully classified patients at risk for ir-ILD development.ConclusionsThe incidence of ir-ILD was substantially higher in the clinical setting. Assessment of spirometry and daily dyspneic symptoms before ICI treatment may be useful in monitoring and managing patients with NSCLC.     

Post-operative Treatment with Cisplatin and Vinorelbine in Chinese Patients with Non-small Cell Lung Cancer: A Clinical Prospective Analysis of 451 Patients

Purpose: To determine the efficacy of post-operative chemotherapy with cisplatin plus vinorelbine (NP) inChinese patients with non-small cell lung cancer (NSCLC). Methods: A total of 451 patients with NSCLCs atstages I, II, and IIIA after surgical resection were treated with cisplatin plus vinorelbine for 4 cycles or volunteersobserved between January 2002 and November 2004 and were followed for five years. The therapeutic efficacywas evaluated with reference to overall survival (OS) and disease-free survival (DFS), and adverse effects werealso recorded. Potential factors affecting the lengths of OS and DFS were analyzed by multivariate analysis.Results: Most patients (86.7%) completed at least 4 cycles of treatment. Patients with chemotherapy survivedsignificantly longer than those in the observation group (p<0.001). The absolute improvements in the 2 and 5-yearOS were 3.8% [hazard ratio (HR) =0.674, 95% confidence interval (CI): 0.554-0.820, P<0.0001] and 13.0%(HR=0.732, 95% CI: 0.579-0.926, P=0.009), respectively. The improvement at 4-year DFS was 2.1% (HR=0.327,95% CI: 0.214-0.500, P<0.0001). Stratification analysis revealed that older age, histological type, pathologicaldegree, but not the gender and smoking status, are independent factors affecting the length of survival in thispopulation. Many patients (63.3%) had grade 1-III tolerable adverse effects, and there was no treatment-relateddeath. Conclusions: Post-operative chemotherapy with NP regimen is effective and tolerable in Chinese patientswith NSCLC.     

Hyperprogressive Disease in Patients With Urothelial Carcinoma or Renal Cell Carcinoma Treated With PD-1/PD-L1 Inhibitors

BackgroundA rapid progression pattern called hyperprogressive disease (HPD) has been observed during early cycles of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy. Data regarding HPD in patients with genitourinary cancer are limited.Patients and MethodsWe included 203 patients with genitourinary cancer treated with PD-1/PD-L1 inhibitors between February 2015 and June 2018. HPD was defined as a greater than 50% increase in tumor burden, greater than 2-fold increase in tumor growth rate, or development of extensive (10 or more) new lesions.ResultsPatients (n = 102) with renal cell carcinoma (RCC) and patients (n = 101) with urothelial carcinoma (UC) were included. HPD was observed in 13 (6.4%) patients. The median overall survival for patients with progressive disease and HPD was 7.3 months and 3.5 months, respectively. HPD occurred more frequently in patients with UC than in those with RCC (11.9% vs. 0.9%; P = .01). Multivariate analysis showed that UC and creatinine above 1.2 mg/dL were independent predictive factors for HPD. A 30% increase in lymphocyte number following PD-1/PD-L1 inhibitor treatment was a negative predictor of HPD. The incidence of HPD in patients with UC treated with paclitaxel-based chemotherapy was one-third of those treated with PD-1/PD-L1 inhibitors.ConclusionHPD developed predominantly in patients with UC, and the incidence of HPD in patients with RCC was negligible. Treatment with PD-1/PD-L1 inhibitors should be prescribed with caution in patients with UC and creatinine above 1.2 mg/dL.