Phase II Trial of Combination Nab-paclitaxel and Gemcitabine in Non–squamous Non–small Cell Lung Cancer After Progression on Platinum and Pemetrexed

BackgroundBetter therapies are needed to improve survival in metastatic non–small cell lung cancer (NSCLC). Given the synergy of combination nab-paclitaxel and gemcitabine in metastatic pancreatic cancer and their individual activity in advanced NSCLC, we sought to determine whether the same combination would confer a therapeutic benefit in the second-line therapy of recurrent or metastatic non–squamous (NSQ) NSCLC.Materials and MethodsThis single-arm phase II trial of nab-paclitaxel and gemcitabine was performed from June 2015 to April 2020 at an academic referral cancer center. Patients with advanced NSQ-NSCLC whose disease progressed on first-line pemetrexed plus platinum +/- immunotherapy were enrolled. Patients received intravenous nab-paclitaxel 100 mg/m² and gemcitabine 1000 mg/m² on days 1 and 8 of each 21-day cycle. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Safety and tolerability were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.ResultsThirty-seven patients (15 men [41%] and 22 women [59%]; median age, 66 years [range, 41-81 years]) were accrued. ORR was 13.5% (95% CI, 2.5-24.5%). DCR was 59.5% (95% CI, 43.5-75.5%). Median PFS was 2.6 months (95% CI, 1.4-3.8 months). Median OS was 6.2 months (95% CI, 4.2-8.2 months). 1-year OS was 24% (95% CI, 10-38%). Safety and tolerability were similar to other second-line chemotherapies, although there was an 11% incidence of grade 2-3 pneumonitis.ConclusionCombination nab-paclitaxel and gemcitabine after platinum and pemetrexed for NSQ-NSCLC was not associated with greater efficacy than would be expected for single-agent chemotherapy in this setting. The higher-than-expected risk of pneumonitis was also concerning.Trial RegistrationClinicalTrials.gov Identifier: NCT02303977Micro-AbstractIn this phase II trial, 37 patients with metastatic non–squamous non–small cell lung cancer were treated with nab-paclitaxel/gemcitabine in second-line. ORR = 13.5% (95% CI, 2.5%-24.5%). Median PFS = 2.6 months (95% CI, 1.4-3.8 months). Median OS = 6.2 months (95% CI, 4.2-8.2 months). Nab-paclitaxel and gemcitabine was not associated with greater efficacy than would be expected for single-agent chemotherapy in this setting.     

Effect of front-line chemotherapy on circulating CK-19 mRNA-positive cells in patients with metastatic breast cancer

Purpose

The incidence of lung cancer in patients with interstitial lung disease (ILD) is higher than in the general population; however, the clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with ILD remain unclear. This study was conducted to elucidate the safety and efficacy of palliative chemotherapy with gemcitabine or pemetrexed, both in combination with a platinum agent in NSCLC patients with ILD.

Patients and methods

Patients with advanced or recurrent NSCLC and ILD who received gemcitabine or pemetrexed in combination with a platinum agent as first-line chemotherapy were retrospectively analyzed. Clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), in addition to the acute exacerbation of ILD after chemotherapy were investigated.

Results

Between January 2007 and December 2011, 52 patients were analyzed. The median age at chemotherapy was 67. Thirty-two patients (61.5 %) had adenocarcinoma histology. With respect to the types of ILD, idiopathic interstitial pneumonia (IIP) and non-IIP were observed in 42 (80.8 %) and 10 (19.2 %) patients, respectively. The FEV1 level was less than 80 % of the predicted value in 15 of the 41 patients in whom it was measured. The overall response rate was 42.3 % (95 % CI 28.8–55.9), and the median PFS was 5.4 months (95 % CI 4.6–6.2). The median OS was 7.9 months (95 % CI 5.5–10.3), and the 1-year survival rate was 31.7 % (95 % CI 19.0–44.4). Eight patients (15.4 %) died within 3 months of first-line chemotherapy. Multivariate analysis demonstrated that a heavy smoking history (40 or more pack-year smoking history) was an independent adverse prognostic factor for OS. An acute exacerbation of ILD (AE-ILD) caused by first-line chemotherapy was noted in 5.8 % of patients.

Conclusion

Our results suggest that gemcitabine or pemetrexed in combination with platinum agents could be a feasible option for advanced NSCLC with ILD with some risk of AE-ILD or early death. To establish the efficacy of palliative chemotherapy for patients with NSCLC and ILD, further well-controlled prospective studies are needed.     

TTD consensus document on the diagnosis and management of exocrine pancreatic cancer

Exocrine pancreatic cancer (PC) is a very aggressive and heterogeneous tumor with several cellular signaling pathways implicated in its pathogenesis and maintenance. Several risk factors increase the risk of developing PC. Therapeutic strategies used are dictated by the extent of disease. Supportive treatment is critical because of the high frequency of symptoms. For localized disease, surgery followed by adjuvant gemcitabine is the standard. Neoadjuvant and new adjuvant chemotherapy regimens are being evaluated. Locally advanced disease should respond best guided by a multidisciplinary team. Various treatment options are appropriate such as chemotherapy alone or chemoradiotherapy with integration of rescue surgery if the tumor becomes resectable. In metastatic disease, chemotherapy should be reserved for patients with ECOG 0–1 using Folfirinox or gemcitabine plus nab-paclitaxel as the most recommended options. Several therapeutic strategies targeting unregulated pathways are under evaluation with an unmet need for biomarkers to guide management.     

Real World First-Line Treatments and Outcomes of Nab-Paclitaxel Plus Gemcitabine,mFOLFIRINOX and GEMOX in Unresectable Pancreatic Cancer from a Chinese Single Institution

Background: There have not been any head-to-head prospective studies to compare the effects of different chemotherapy regimens as first-line treatments for unresectable pancreatic cancer (UPC). We aimed to compare the effectiveness of nab-paclitaxel plus gemcitabine, mFOLFIRINOX and gemcitabine plus oxaliplatin (GEMOX) as first-line treatments by using real-world data from Chinese patients. Methods: We retrospectively included patients with UPC treated with nab-paclitaxel plus gemcitabine, mFOLFIRINOX or GEMOX as a first-line treatment at Sun Yat-sen University Cancer Center. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed. Results: A total of 117 patients were administered nab-paclitaxel plus gemcitabine (n = 62), mFOLFIRINOX (n = 30) or GEMOX (n = 25) as first-line chemotherapy. The median OS was 11.1, 10.1 and 10.2 months (p = 0.75) in the nab-paclitaxel plus gemcitabine, mFOLFIRINOX and GEMOX, respectively. The ORR was similar among the three groups (24%, 23% and 32%, p = 0.76) and the DCR was higher in the nab-paclitaxel-gemcitabine group (82%) than the other two groups (60% and 64%, p = 0.04). The most common adverse events of grade 3 or 4 were neutropenia (32%, 28% and 5%), peripheral neuropathy (13%, 16% and 0) and fatigue (9%, 16% and 5%). Febrile neutropenia occurred in 2%, 4% and 5% of the patients in the three groups. Conclusion: In the first line treatment of UPC, our results suggest that nab-paclitaxel plus gemcitabine was associated with a higher DCR than mFOLFIRINOX or GEMOX, while all groups demonstrated similar OS, PFS and ORR.     

Results from the prospective German TPK clinical cohort study: Treatment algorithms and survival of 1,174 patients with locally advanced,inoperable, or metastatic pancreatic ductal adenocarcinoma

Pancreatic cancer is a highly lethal malignancy. Developments in recent years have broadened our therapeutic armamentarium. Novel drugs such as nab-paclitaxel, liposomal irinotecan and chemotherapy regimens such as FOLFIRINOX have been successfully tested in clinical trials. Data on patients outside of clinical trials are scarce but necessary to assess and improve the standard of care. We present data on treatment and survival of 1,174 patients with locally advanced, inoperable, or metastatic pancreatic ductal adenocarcinoma. Between February 2014 and June 2017, patients were recruited by 104 sites at start of first-line therapy into the ongoing, prospective clinical cohort study TPK (Tumour Registry Pancreatic Cancer). As first-line therapy, 89% of patients received one of the three treatment regimens: gemcitabine monotherapy (23%), nab-paclitaxel plus gemcitabine (42%), or FOLFIRINOX (24%). The corresponding subgroups differed: Patients receiving gemcitabine monotherapy were older and more comorbid (median age 78 years, 73% ECOG ≥ 1) than patients receiving nab-paclitaxel plus gemcitabine (median age 71, 64% ECOG ≥ 1) or patients receiving FOLFIRINOX (median age 60, 52% ECOG ≥ 1). At least 40% of patients died before receiving second-line treatment. First-line progression-free survival was 4.6 months (95% CI: 3.7–5.2) for gemcitabine, 5.6 months (95% CI: 5.0–6.2) for nab-paclitaxel plus gemcitabine, and 6.3 months (95% CI: 5.5–6.9) for FOLFIRINOX. Our data represent the treatment reality in a German community setting. Although there are no stringent inclusion criteria for our cohort study, overall survival is comparable to that reported by randomised clinical trials.     

First‐Line Treatment Patterns and Clinical Outcomes in Patients With HER2‐Positive and Hormone Receptor‐Positive Metastatic Breast Cancer From registHER

Background.

Limited data are available describing the natural history of patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer (MBC). We examined first-line treatment patterns and clinical outcomes in patients with HER2-positive, HR-positive MBC in a real-world setting.

Methods.

registHER is a prospective, observational cohort of 1,023 patients with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up time: 27 months). Demographics, first-line treatment patterns, and clinical outcomes were examined for 530 HER2-positive, HR-positive patients. Progression-free survival (PFS) and overall survival (OS) times were examined. Multivariate analyses adjusted for baseline demographic and prognostic factors.

Results.

HER2-positive, HR-positive patients receiving first-line trastuzumab plus hormonal therapy had significantly longer PFS times than patients who received hormonal therapy only (13.8 vs. 4.8 months; adjusted hazard ratio [HR]: 0.37, 95% confidence interval [CI]: 0.22–0.60); a nonsignificant reduction in OS time was observed (adjusted HR: 0.55, 95% CI: 0.27–1.14). Compared with patients who received first-line trastuzumab plus chemotherapy, patients who received first-line trastuzumab plus chemotherapy and hormonal therapy had longer median PFS times (20.4 months vs. 9.5 months; adjusted HR: 0.53, 95% CI: 0.42–0.68); a statistically significant reduction in risk of death was observed (adjusted HR: 0.50, 95% CI: 0.36–0.70). Sequential use of chemotherapy and hormonal therapy was associated with improved OS times when compared with concurrent use (adjusted PFS HR: 0.81, 95% CI: 0.54–1.21; adjusted OS HR: 0.48, 95% CI: 0.26–0.89).

Conclusions.

These real-world data in patients with HER2-positive/HR-positive MBC provide evidence that, with or without chemotherapy, dual targeting of HRs and HER2 receptors is associated with significantly prolonged PFS and OS times.     

Prognostic significance of preexisting interstitial lung disease in Japanese patients with small-cell lung cancer

BackgroundIn Japan, iatrogenic acute exacerbation of interstitial lung disease (ILD) is a serious complication in patients with lung cancer and simultaneous ILD. Results of some reports suggest that patients with ILD and small-cell lung cancer (SCLC) might benefit from chemotherapy, but the influence of ILD on prognosis is unclear.Patients and MethodsRetrospective study of patients with SCLC with or without ILD. Between April 2006 and March 2011, 122 patients with SCLC who were receiving platinum-based combination chemotherapy participated.ResultsTwenty-eight patients (23.0%) had ILD at diagnosis. Pneumonitis associated with chemotherapy, including acute exacerbation–ILD was significantly increased in patients with preexisting ILD (8/28 vs. 2/94; P = .0001). In patients receiving chemotherapy alone, response rates and median progression-free survival of first-line chemotherapy in patients with or without preexisting ILD was not significantly different (P = .26; 20/26 vs. 52/60 and P = .089; 4.4 months vs. 5.4 months, respectively). The median overall survival of all patients was 15.5 months, but those without preexisting ILD survived significantly longer (P = .0010; 17.8 months vs. 10.7 months). Multivariate analysis revealed that performance status of 0 or 1 (hazard ratio [HR] 0.19 [95% confidence interval {CI}, 0.10-0.37]; P < .0001) limited disease (HR 0.42 [95% CI, 0.23-0.73]; P = .0017), and no preexisting ILD (HR 0.36 [95% CI, 0.19-0.69]; P = .0027) were significantly associated with longer overall survival.ConclusionPatients with SCLC and ILD might benefit from chemotherapy, but preexisting ILD is an independent prognostic factor for poorer survival.     

Cardiac toxicity associated with anthracycline‐containing chemotherapy in older women with breast cancer

BACKGROUND:

The purpose of this study was to determine the risk of chemotherapy‐associated cardiac toxicity, including cardiac dysrhythmia, cardiomyopathy, congestive heart failure, ischemic heart disease, and conduction disorders among breast cancer patients with up to 16 years of follow‐up.

METHODS:

The authors studied 19,478 women aged >65 diagnosed with breast cancer in 1991‐1997 from 16 regions in the Surveillance, Epidemiology, and End Results program. Incidence density and cumulative incidence of cardiac toxicities were calculated, and the time‐to‐event (cardiac toxicity) analysis was conducted by using the Cox hazard regression model.

RESULTS:

The excess cumulative incidence of congestive heart failure in Year 10 among patients receiving anthracycline‐containing chemotherapy compared with patients without chemotherapy was 4.7% (31.9% vs 27.2%). After adjusting for patient and tumor characteristics, patients receiving anthracyclines were 25% more likely to have congestive heart failure compared with those without chemotherapy (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07‐1.46). Those receiving other agents did not have a significantly elevated risk of developing congestive heart failure. The adjusted risk of cardiomyopathy was 2‐fold higher in women who received anthracyclines (HR, 1.95; 95% CI, 1.44‐2.62) and was 16% higher in those receiving other agents (HR, 1.16; 95% CI, 0.97‐1.39) compared with those without chemotherapy. The increased risk for developing congestive heart failure, cardiomyopathy, and cardiac dysrhythmias in association with chemotherapy were similar after adjusting for hypertension and diabetes. The risk of ischemic heart disease and conduction disorders were not significantly different among the 3 groups.

CONCLUSIONS:

Anthracycline‐containing chemotherapy regimens were associated with an increased risk of congestive heart failure, cardiomyopathy, and cardiac dysrhythmias, but not significantly associated with ischemic heart disease or conduction disorders. Cancer 2009. © 2009 American Cancer Society.     

Patterns of chemotherapy,toxicity, and short-term outcomes for older women receiving adjuvant trastuzumab-based therapy

Limited data are available regarding patterns of chemotherapy receipt and treatment-related toxicities for older women receiving adjuvant trastuzumab-based therapy. We used surveillance, epidemiology and end results (SEER)-Medicare data to identify patients ≥66 years with stage I–III breast cancer treated during 2005–2009, who received trastuzumab-based therapy. We examined patterns of chemotherapy receipt, and using multivariable logistic regression, we examined associations of age and comorbidity with non-standard chemotherapy. In propensity-weighted cohorts of women receiving standard and non-standard trastuzumab-based therapy, we also examined rates of (1) hospital events during the first 6 months of chemotherapy and (2) short-term survival. Among 2,106 women, 29.7 % were aged ≥76 and 66 % had a comorbidity score = 0. Overall, 31.3 % of women received non-standard chemotherapy. Compared to patients aged 66–70, older patients more often received non-standard chemotherapy [adjusted odds ratio (OR) = 4.1, 95 % confidence interval (CI) = 3.40–4.92 (ages 76–80); OR = 15.3, 95 %CI = 9.92–23.67 (age ≥ 80)]. However, comorbidity was not associated with receipt of non-standard chemotherapy. After propensity score adjustment, hospitalizations were more frequent in the standard (vs. non-standard) group (adjusted OR = 1.7, 95 % CI = 1.29–2.24). With a median follow-up of 2.8 years, 276 deaths occurred; the adjusted hazard ratio (HR) for death was lower in standard versus non-standard treated women (HR = 0.69, 95 % CI = 0.52–0.91). Among a population-based cohort of older women receiving trastuzumab, nearly one-third received non-standard chemotherapy, with the highest rates among the oldest women. Non-standard chemotherapy was associated with fewer toxicity-related hospitalizations but worse survival. Further exploration of treatment toxicities and outcomes for older women with HER2-positive breast cancer is warranted.     

非小细胞肺癌吉西他滨诱导化疗+放疗后放射性肺炎危险因素及剂量学分析

目的 对非小细胞肺癌(NSCLC)吉西他滨化疗后急性放射性肺炎(ARP)的发生情况进行总结,阐明吉西他滨诱导化疗后发生急性放射性肺炎的高危因素及剂量学限制。方法 回顾性分析2010-2017年间浙江省肿瘤医院放疗科收治的接受吉西他滨化疗+胸部放疗的NSCLC患者191例,收集患者的基本信息、放化疗情况以及ARP情况。Logistic法单因素和多因素分析影响ARP发生的因素。结果 共49例患者发生≥2级ARP,占25.7%。单因素分析显示吉西他滨累积剂量≥9.0g发生ARP概率是<9.0g的3.45倍(P=0.015),放疗剂量≥50Gy与ARP发生有关(P=0.008),放化疗间隔时间在10周内ARP发生风险增加7.69倍(P=0.047);双肺V5Gy、V20Gy、V30Gy和平均肺剂量(MLD)均能有效预测ARP发生(P≤0.001)。多因素分析仅有放疗剂量(P=0.044)和V5Gy(P=0.02)是ARP发生的预测因素。结论 对于接受吉西他滨化疗的NSCLC患者来说,吉西他滨累积剂量、化放疗间隔时间以及放疗剂量均与ARP的发生有关,同时应当限制双肺V5Gy、V20Gy、V30Gy和MLD,以减少ARP的发生。     

Efficacy and treatment-related adverse events of gemcitabine plus nab-paclitaxel for treatment of metastatic pancreatic cancer “in a Korean” population: A single-center cohort study

Pancreatic cancer has poor prognosis because of its rapid progression and treatment resistance. Based on the results of the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), a combination regimen of gemcitabine with nab-paclitaxel is currently used as standard therapy for the treatment of metastatic pancreatic cancer. However, because studies in Asian populations are lacking, we investigated the treatment efficacy and safety of this combination therapy in Korean population. Patients with metastatic pancreatic cancer (n=81) treated with gemcitabine and nab-paclitaxel (1,000 and 125 mg/m², respectively) as the first-line chemotherapy from January 2016 were identified using the Severance Hospital Pancreatic Cancer Cohort Registry. Treatment efficacy and treatment-related adverse events (AEs) were analyzed. The median follow-up period was 10.7 months (range, 1.5–23.3 months). Median overall survival, progression-free survival, and objective response rates were 12.1 months (95% confidence interval [CI], 10.7–not estimable), 8.4 months (95% CI, 5.0–11.8), and 46.9%, respectively. The incidence of grade ≥3 neurotoxicity and neutropenia were 18.5% and 46.9%, respectively. Febrile neutropenia and grade ≥3 gastrointestinal AEs occurred in 13 (16.0%) and 16 (19.8%) patients, respectively. Dose reductions because of AEs were required in 60.5% of patients. The combination of gemcitabine with nab-paclitaxel is an effective anti-cancer regimen in Korean population of patients with metastatic pancreatic adenocarcinoma. However, careful monitoring and management are required because of occurrence of treatment-related AEs.     

Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma

BACKGROUND: The current study was conducted to characterize the risks and clinical consequences of oral mucositis (OM) in patients with head and neck carcinoma (HNC) who are receiving radiation therapy. METHODS: Data regarding 450 HNC patients who had received radiation therapy were collected via chart review from 154 U.S. medical and radiation oncologists. Information obtained included patient characteristics, treatments received, highest recorded grade of OM during radiation therapy (none, mild, moderate, or severe), and outcomes potentially associated with mucosal injury. RESULTS: The mean age (+/- standard deviation [SD]) of the study subjects was 61.3 years (12.3 yrs); the majority of patients (80%) were men. Primary tumor locations included the oropharynx (26.4%), larynx (26.4%), oral cavity including the lip (24.4%), hypopharynx (13.6%), and nasopharynx (9.1%). The majority of tumors were new and were classified as AJCC Stages III or IV. The majority of patients (83%) received standard radiation therapy; the mean (+/- SD) cumulative dose was 6285 centigrays (cGy) (+/- 1158 cGy). Approximately 33% of the patients received concomitant chemotherapy. The majority of patients (83%) developed OM; 29% developed severe OM. Patients with severe OM were more likely to have nasopharyngeal or oropharyngeal tumors (adjusted odds ratio [OR] of 10.1 [95% confidence interval (95% CI), 2.1-49.9] and 6.9 [95% CI, 2.4-19.7], respectively), and to have received cumulative radiation doses > 5000 cGy (OR of 10.4; 95% CI, 2.9-37.1) and concomitant chemotherapy (OR of 3.3; 95% CI, 1.4-8.0). Patients with OM had more unplanned breaks in radiation therapy (OR of 3.8; 95% CI, 1.7-8.5) and hospital admissions (OR of 3.5; 95% CI, 1.3-9.5). CONCLUSIONS: HNC patients with nasopharyngeal or oropharyngeal tumors, and those who receive cumulative radiation doses > 5000 cGy or concomitant chemotherapy, are more likely to develop OM. Patients with OM are at a higher risk of unplanned breaks in radiation therapy and hospitalization.     

Real-World Evaluation of Factors for Interstitial Lung Disease Incidence and Radiologic Characteristics in Patients With EGFR T790M–positive NSCLC Treated With Osimertinib in Japan

IntroductionUsing real-world Japanese postmarketing data, we characterized interstitial lung disease (ILD) development during the second- or later-line osimertinib treatment for EGFR mutation-positive NSCLC. Retrospective radiologic image evaluation of patients developing ILD was also performed.MethodsPatients who had ILD events reported as an adverse drug reaction by their physicians and who were assessed as having developed ILD as assessed by an ILD expert committee in Japan were included.ResultsAmong 3578 patients, 252 ILD events were reported in 245 patients (6.8%) by their attending physicians. The median (range) time to the first onset of ILD after osimertinib treatment initiation was 63.0 (5–410) days, and 29 patients with a fatal outcome were reported. The ILD expert committee assessed 231 of 3578 patients (6.5%) as having ILD. A previous history of nivolumab therapy (adjusted OR: 2.84; 95% confidence interval: 1.98–4.07) and a history or concurrence of ILD (3.51; 2.10–5.87) were identified as factors potentially associated with ILD onset during osimertinib treatment. In patients who had received a previous nivolumab treatment, the number and proportion of patients developing ILD were highest for patients who discontinued nivolumab treatment within the first month before initiating osimertinib; trends for decreasing incidence and proportion were observed, with an increasing duration between the end of nivolumab treatment and the initiation of osimertinib treatment.ConclusionsThe frequency of ILD was consistent with the known osimertinib safety profile in the Japanese population. A history or concurrence of ILD and history of previous nivolumab therapy are factors potentially associated with ILD onset during osimertinib treatment.     

A Randomized,Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407

IntroductionIn the randomized KEYNOTE-407 study (ClinicalTrials.gov, NCT02775435), pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel (chemotherapy) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC. We report updated efficacy outcomes from the protocol-specified final analysis and, for the first time, progression on next line of treatment.MethodsEligible patients were randomized to chemotherapy plus either pembrolizumab (n = 278) or placebo (n = 281). After positive results from the second interim analysis, patients still receiving placebo could cross over to pembrolizumab monotherapy at the time of confirmed progressive disease. The primary end points were OS and PFS. PFS-2 (time from randomization to progression on next-line treatment/death, whichever occurred first) was an exploratory end point.ResultsAfter median (range) follow-up of 14.3 (0.1–31.3) months, pembrolizumab plus chemotherapy continued to exhibit a clinically meaningful improvement over placebo plus chemotherapy in OS (median, 17.1 mo [95% confidence interval (CI): 14.4‒19.9] versus 11.6 mo [95% CI: 10.1‒13.7]; hazard ratio [HR], 0.71 [95% CI: 0.58‒0.88]) and PFS (median, 8.0 mo [95% CI: 6.3‒8.4] versus 5.1 mo [95% CI: 4.3‒6.0]; HR, 0.57 [95% CI: 0.47‒0.69]). PFS-2 was longer for patients randomized to first-line pembrolizumab plus chemotherapy (HR, 0.59 [95% CI: 0.49‒0.72]). Grade 3 to 5 adverse events occurred in 74.1% and 69.6% of patients receiving pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively.ConclusionsPembrolizumab plus chemotherapy continued to exhibit substantially improved OS and PFS in patients with metastatic squamous NSCLC. The PFS-2 outcomes support pembrolizumab plus chemotherapy as a standard first-line treatment in patients with metastatic squamous NSCLC.     

Infused therapy and survival in older patients diagnosed with metastatic breast cancer who received trastuzumab

We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane. In multivariate analysis, trastuzumab plus chemotherapy was associated with a lower adjusted cancer mortality rate (Hazard Ratio [HR] 0.54; 95% Confidence Interval [CI] 0.39-0.74; p < .001) than trastuzumab alone among patients who received trastuzumab as part of first-line therapy. Adding chemotherapy to first-line trastuzumab for metastatic breast cancer is associated with improved cancer survival.     

白蛋白结合型紫杉醇联合吉西他滨动脉灌注治疗进展期胰腺癌的安全性和有效性回顾性研究

背景与目的：白蛋白结合型紫杉醇联合吉西他滨（nab-paclitaxel combined with gemcitabine,AG）方案静脉化疗是进展期胰腺癌有效治疗方案之一,动脉灌注化疗（transcatheter arterial chemotherapy,TAC）具有增强疗效并降低不良反应的优势,观察AG方案经TAC治疗进展期胰腺癌患者的有效性和安全性。方法：回顾性分析2016年1月—2019年6月复旦大学附属肿瘤医院收治的63例接受治疗的进展期胰腺癌患者,患者均经病理学检查确诊为胰腺导管腺癌,其中Ⅲ期15例,Ⅳ期48例,所有患者接受经动脉灌注化疗和（或）栓塞治疗,动脉灌注化疗用药方案为盐酸吉西他滨1 000 mg/m ² 联合白蛋白结合型紫杉醇125 mg/m ² ,灌注时间≥10 min,伴有肝转移者同时行供血动脉栓塞。结果：63例患者中,术中行数字减影血管造影（digital subtraction angiography,DSA）可见胰腺肿瘤和肝转移灶动脉供血比例分别为66.67%和35.29%;接受治疗1次4例,2次6例,3次6例,4次及以上47例,治疗次数最多为9次,间隔时间为21～45 d。1年生存率为36.51%,中位生存期（median overall survival,mOS）为9.2个月,6个月无进展生存（progression-free survival,PFS）率为44.44%,中位PFS（median PFS,mPFS）为4.7个月。多因素分析显示KPS≥80、Ⅲ期与较长的生存期相关,接受多次动脉灌注化疗和（或）栓塞是良好的生存预后相关因素。发生治疗相关的Ⅲ度及以上血液学不良反应包括中性粒细胞减少（3.17%）和血小板下降（4.76%）,非血液学不良反应包括乏力（6.35%）、恶心呕吐（9.52%）、腹泻（4.76%）和转氨酶升高（4.76%）;17.46%和22.22%的患者出现发热及肝区疼痛栓塞综合征,所有不良反应经治疗后均好转,无治疗相关性死亡病例。结论：白蛋白结合型紫杉醇联合吉西他滨经动脉灌注治疗进展期胰腺癌具有较好的安全性,不良反应与静脉给药相比有所减少,可有效地控制病情,使患者生存获益。     

Comparative Effectiveness and Resource Usage in Patients Receiving First-line Taxane-based Chemotherapy for Stage IV Non–Small-cell Lung Cancer in a US Community Oncology Setting

BackgroundWeekly (qw) nanoparticle albumin-bound (nab)-paclitaxel was approved for advanced non–small-cell lung cancer based on the results from a phase III trial in which nab-paclitaxel/carboplatin demonstrated a significantly greater response rate compared with paclitaxel/carboplatin every 3 weeks (q3w). Little information exists on relative real-world results.Materials and MethodsThe present retrospective study used data from a national electronic medical record database. Patients receiving first-line nab-paclitaxel qw, paclitaxel qw, or paclitaxel q3w for stage IV non–small-cell lung cancer (NSCLC) were identified. The total cumulative dose, time to treatment discontinuation (TTD), and database persistence (a proxy measure for survival) were analyzed for all patients and for the squamous and elderly subgroups.ResultsA total of 114, 208, and 153 patients received nab-paclitaxel qw, paclitaxel qw, and paclitaxel q3w, respectively. In the corresponding treatment arms, the median age was 72, 69, and 67 years; 56%, 48%, and 37% were aged ≥ 70 years; and 75%, 43%, and 23% had squamous cell NSCLC. The total cumulative dose was significantly greater with nab-paclitaxel qw. The TTD was longer with nab-paclitaxel qw than with paclitaxel qw (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.40-0.72; P < .001) or with paclitaxel q3w (HR, 0.53; 95% CI, 0.38-0.73; P < .001). Database persistence was longer with nab-paclitaxel qw than with paclitaxel qw (HR, 0.56; 95% CI, 0.39-0.79; P = .001) or with paclitaxel q3w (HR, 0.52; 95% CI, 0.34-0.78; P = .002). The TTD after experiencing any hematologic adverse event was longer with nab-paclitaxel qw. The findings were consistent across the subgroup analyses.ConclusionIn a real-world setting, nab-paclitaxel qw was associated with a significantly greater cumulative dose and significantly longer TTD and database persistence compared with paclitaxel qw and paclitaxel q3w.     

The survival impact of delayed surgery and adjuvant chemotherapy on stage II/III rectal cancer with pathological complete response after neoadjuvant chemoradiation

Neoadjuvant concurrent chemoradiation (CCRT) is standard treatment for clinical stage II/III rectal cancers. However, whether patients with pathological complete response (pT0N0, pCR) should receive adjuvant chemotherapy and whether delayed surgery will influence the pCR rate remains controversial. A nationwide population study was conducted using the Taiwan Cancer Registry Database from January 2007 to December 2013. Kaplan‐Meier survival analysis was performed. Cox proportional hazards models were used to estimate multivariate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). Of the 1,914 patients who received neoadjuvant CCRT, 259 (13.6%) achieved pCR and had better survival (adjusted HR: 0.37, 95% CI: 0.24‐0.58; p < 0.001). The cumulative rate of pCR rose up to 83.4% in the 9th week and slowly reached a plateau after the 11th week. Among the patients with pCR, those who received adjuvant chemotherapy had no survival benefits compared to those without adjuvant chemotherapy (adjusted HR: 0.72, 95 CI: 0.27–1.93; p = 0.52). By subgroup analysis, those younger than 70‐year old and received adjuvant chemotherapy had better survival benefit than those without adjuvant chemotherapy (adjusted HR: 0.19, 95% CI: 0.04–0.97; p = 0.046). Delayed surgery by 9–12 weeks after the end of neoadjuvant CCRT can maximize the pCR rate, which is correlated with better survival. Adjuvant chemotherapy may be considered in patients with pCR and aged <70‐year old, but further prospectively randomized controlled trials are warranted to validate these findings.     

Myeloid leukaemia following therapy for a first primary cancer

To evaluate the risk of second primary myeloid leukaemia due to radiotherapy and chemotherapy administered for a first primary cancer, we conducted a population-based case-control study consisting of 97 cases and 194 controls matched on age, date of diagnosis, and site of initial primary cancer among residents of 13 counties in western Washington State. The risk of myeloid leukaemia in patients who received cyclophosphamide as part of their chemotherapy regimen was 7.4 (95% confidence interval 1.3-43.8). This risk was not altered appreciably by the administration of radiotherapy. Compared to patients not receiving any chemotherapy, the relative risk among patients who received prednisone in combination with cyclophosphamide (odds ratio 44.4 95% confidence interval 4.0-496.2) was nearly four times that among patients receiving cyclophosphamide without this steroid (odds ratio 12.6 95% confidence interval 2.4-64.9). The relative risk of second primary myeloid leukaemia in patients who received both prednisone and drugs other than cyclophosphamide (odds ratio 64.2 95% confidence interval 2.6-1582) was 20 times that among patients receiving drugs other than cyclophosphamide and no prednisone (odds ratio 3.2 95% confidence interval 0.6-16.9). These risk estimates were higher when the analysis was restricted to acute myeloid leukaemia. There was no increased risk of second primary myeloid leukaemia associated with radiotherapy. The single unique finding is that the use of prednisone in chemotherapy regimens may enhance the leukaemogenic effect of other chemotherapy drugs.