Immune Checkpoint Inhibitors for Patients With Advanced Non–Small-Cell Lung Cancer: A Systematic Review

Second-line treatment options are limited for patients with advanced non–small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC. Medline, Embase, and PubMed were searched for randomized controlled trials comparing treatment with immune checkpoint inhibitors against treatment with chemotherapy in patients with stage IIIB or IV NSCLC. Nine randomized controlled trials with 15 publications were included. A significant overall survival benefit of second-line nivolumab (nonsquamous: hazard ratio [HR] = 0.72, 95% confidence interval [CI], 0.60-0.77; P < .001; squamous: HR = 0.59, 95% CI, 0.44-0.79; P < .001) or second-line atezolizumab (HR = 0.73, 95% CI, 0.62-0.87; P = .0003) or second-line pembrolizumab (in patients with programmed cell death ligand 1 [PD-L1]-positive tumors) (pembrolizumab 2 mg/kg HR = 0.71, 95% CI, 0.58-0.88; P = .0008; pembrolizumab 10 mg/kg HR = 0.61, 95% CI, 0.49-0.75; P < .0001) or first-line pembrolizumab (HR = 0.60, 95% CI, 0.41-0.89; P = .005) compared with chemotherapy was found. The adverse effects were mainly higher in the chemotherapy arms. For patients with advanced stage IIIB/IV NSCLC, the improvement in overall survival outweighed the harms and supported the use of first-line pembrolizumab (in patients with ≥ 50% PD-L1–positive tumors) or second-line nivolumab, atezolizumab, or pembrolizumab (in patients with PD-L1–positive tumors).     

Immune checkpoint inhibitor for patients with advanced biliary tract cancer: A cost-effectiveness analysis

Background and Aims

The increasingly widespread of immune checkpoint inhibitors (ICIs) in the field of antitumors has brought a new dawn for patients with advanced biliary tract cancer (aBTC). However, the choice of treatment needs to be supported by economic evaluation. Therefore, the cost-effectiveness comparison of first-line durvalumab or pembrolizumab plus gemcitabine and cisplatin (GemCis) treatment of aBTC was explored from the perspective of American and Chinese healthcare systems.

Methods

Ground on the TOPAZ-1 and KEYNOTE-966 trials, the Markov model with a 15-year horizon including three health states to imitate cost and effective outcomes was established. Incremental cost-effectiveness ratio (ICER) at willingness-to-pay (WTP) thresholds of $100 000/QALY and $37 408/ALY in the USA and China was used as the most important indicator. Other endpoint indexes included total cost, life years (LYs), quality-adjusted life years (QALYs) and incremental net-health benefit (INHB). To verify the robustness, sensitivity and subgroup analyses were performed.

Results

Durvalumab plus GemCis ($322 211 [2.94 QALYs] and $35 695 [2.76 QALYs]) increased cost (effectiveness) by $63 777 (.22 QALYs) and $5234 (.20 QALYs) than pembrolizumab plus GemCis ($258 434 [2.72 QALYs] and $30 461 [2.56 QALYs]) in the USA and China, respectively. The corresponding ICER was $288 725/QALY and $26 401/QALY, with INHB of −.42 and .06 QALYs, respectively. The cost of ICIs was the most important factor influencing results.

Conclusions

In China, first-line durvalumab plus GemCis versus pembrolizumab plus GemCis was a cost-effective option for patients with aBTC, but not in the USA.     

Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study

BackgroundPembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC).ObjectiveTo evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC.Design, setting, and participantsCohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening.InterventionPembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily.Outcome measurements and statistical analysisThe primary endpoints were safety, confirmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS).Results and limitationsOf 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65–76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22–47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0–6.5) and median OS was 14 mo (95% CI, 10.4–18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1)-positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3–5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design.ConclusionsPembrolizumab plus olaparib had a safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC.Patient summaryPembrolizumab plus olaparib showed antitumor activity and expected safety in patients with metastatic castration-resistant prostate cancer.     

1例帕博利珠单抗致持续4级血小板减少症的病例分析

目的 探讨帕博利珠单抗致持续严重血小板减少症的临床特征和治疗方案。方法 以1例帕博利珠单抗致持续4级血小板减少症的病例分析为切入点，查阅文献，分析其临床特征及治疗方案。结果 数据显示帕博利珠单抗引起严重血小板减少的发生率很低，部分患者经糖皮质激素、环孢素等免疫抑制治疗效果不佳，其原因可能与反复使用程序性死亡受体1（PD-1）抑制剂后体内“免疫刹车”失灵导致自身免疫异常有关。结论 临床医生应权衡利弊，密切监测患者血小板计数，保障患者用药安全。     

The 2022 Updated European Association of Urology Guidelines on the Use of Adjuvant Immune Checkpoint Inhibitor Therapy for Renal Cell Carcinoma

In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient.Patient summaryNew results from three trials of immunotherapy after surgery for kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed.