Caregiver survey in glioblastoma focused on cognitive dysfunction: development and results from a multicenter study.

Aim: To develop a cognitive dysfunction (CD) focused questionnaire to evaluate caregiver burden in glioblastoma. Materials & methods: The survey was developed from stakeholder consultations and a pilot study, and disseminated at eight US academic cancer centers. Caregivers self-reported caring for an adult with glioblastoma and CD. Results: The 89-item survey covered demographics, CD symptoms and caregiver burden domains. Among 185 caregivers, most were white, educated females and reported memory problems as the most common CD symptom. An exposure-effect was observed, with increase in number of CD symptoms significantly associated with greater caregiver burden. Conclusion: This questionnaire could guide caregiver interventions and be adapted for use longitudinally, in community cancer settings, and in patients with brain metastases.

Glioblastoma (GBM) is a very aggressive brain cancer. People who have GBM have trouble remembering things and are unable to do things they used to do. These changes can be very hard. Researchers are trying to better understand what it is like for people who take care of people with GBM (or caregivers). In this study, researchers created a new survey for caregivers. The survey included questions about what caregivers see happening in their loved one with GBM. Caregivers said that memory problems were common. Also, when the patient had more problems the caregiver had a harder time, too. Researchers hope to improve the survey and use it in the future for more studies.

Caregiver burden by treatment and clinical characteristics of patients with glioblastoma.

BACKGROUND: Glioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL). METHODS: Caregiver-patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses. RESULTS: The final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions. CONCLUSION: This study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.

Developing real-world comparators for clinical trials in chemotherapy-refractory patients with gastric cancer or gastroesophageal junction cancer.

BACKGROUND: There are few third-line or later (3L+) treatment options for advanced/metastatic (adv/met) gastric cancer/gastroesophageal junction cancers (GC/GEJC). 3L+ Nivolumab demonstrated encouraging results in Asian patients in the ATTRACTION-2 study compared with placebo (12-month survival, 26% vs 11%), and in Western patients in the single-arm CheckMate 032 study (12-month survival, 44%). This analysis aimed to establish comparator cohorts of US patients receiving routine care in real-world (RW) clinical practice. METHODS: A 2-step matching process generated RW cohorts from Flatiron Health's oncology database (January 1, 2011-April 30, 2017), for comparison with each trial: (1) clinical trial eligibility criteria were applied; (2) patients were frequency-matched with trial arms for baseline variables significantly associated with survival. Median overall survival (OS) was calculated by Kaplan-Meier analysis from last treatment until death. RESULTS: Of 742 adv/met GC/GEJC patients with at least 2 prior lines of therapy, matching generated 90 US RW ATTRACTION-2-matched patients (median OS: 3.5 months) versus 163 ATTRACTION-2 placebo patients (median OS: 4.1 months), and 100 US RW CheckMate 032-matched patients (median OS: 2.9 months) versus 42 CheckMate 032 nivolumab-treated patients (median OS: 8.5 months). Baseline characteristics were generally similar between clinical trial arms and RW-matched cohorts. CONCLUSIONS: We successfully developed RW cohorts for comparison with data from clinical trials, with comparable baseline characteristics. Survival in US patients receiving RW care was similar to that seen in Asian patients receiving placebo in ATTRACTION-2; survival with nivolumab in CheckMate 032 appeared favorable compared with US RW clinical practice.

Correction to: Developing real-world comparators for clinical trials in chemotherapy-refractory patients with gastric cancer or gastroesophageal junction cancer.

ping real-world comparators for.

Characterizing fatigue associated with sunitinib and its impact on health-related quality of life in patients with metastatic renal cell carcinoma.

BACKGROUND: Using phase 3 trial data for sunitinib versus interferon (IFN)-α in treatment-naive patients with metastatic renal cell carcinoma, retrospective analyses characterized sunitinib-associated fatigue and its impact on patient-reported health-related quality of life (HRQoL). METHODS: Patients received sunitinib at a dose of 50 mg/day on a schedule of 4 weeks on/2 weeks off (375 patients) or IFN-α at a dose of 9 MU subcutaneously 3 times per week (360 patients). HRQoL was self-assessed using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-15-item (FKSI-15) questionnaire, with fatigue assessed using its Disease-Related Symptoms subscale. Fatigue was also assessed by providers using Common Terminology Criteria for Adverse Events (CTCAE). A repeated-measures model (M1) and random intercept-slope model (M2) characterized sunitinib-associated fatigue over time. Another repeated-measures model examined the relationship between HRQoL scores and CTCAE fatigue grade. RESULTS: M1 demonstrated that the initial increase in patient-reported fatigue with sunitinib was worst during cycle 1, with mean values numerically better at subsequent cycles; most pairwise comparisons of consecutive CTCAE fatigue cycle means were not found to be statistically significant. M2 demonstrated that the overall trend (slope) for patient-reported and CTCAE fatigue with sunitinib was not statistically different from 0. The relationship between most HRQoL scores and CTCAE fatigue was close to linear regardless of treatment, with lower scores (worse HRQoL) corresponding to higher fatigue grade. The majority of HRQoL scores were better with sunitinib versus IFN-α for the same CTCAE fatigue grade. CONCLUSIONS: Patients reported worse fatigue during the first sunitinib cycle. However, in subsequent consecutive cycles, less fatigue was reported with no statistically significant worsening. CTCAE fatigue assessment may not fully capture patient treatment experience.

Brain metastases in clinical trial participants with KRAS-mutated advanced non-small cell lung cancer receiving docetaxel: Pooled data analysis.

OBJECTIVES: Limited data are available on central nervous system (CNS) efficacy with standard-of-care therapies for KRAS-mutated (KRASmut) advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the incidence and progression of brain metastases in KRASmut advanced NSCLC treated with docetaxel using pooled data from historical clinical trials. MATERIALS AND METHODS: Data from phase 2/3 trials of docetaxel-containing regimens in advanced NSCLC were sourced from the Medidata platform. Analysis was restricted to stage IIIB-IV KRASmut NSCLC with disease progression after ≥ 1 systemic anticancer therapy. Participants with asymptomatic, treated, and stable brain metastases were included. Endpoints included 12-month CNS disease control rate (CNS-DCR) and CNS progression per Response Evaluation Criteria in Solid Tumors; progression-free survival (PFS); and overall survival (OS). Data were pooled and analyses stratified by baseline brain metastases status. RESULTS: A total of 595 participants were included in the analysis (62 [10%] with baseline brain metastases and 533 [90 %] without). Among participants with brain metastases, 17 (27.4 %) had CNS progression during docetaxel treatment and 12-month CNS-DCR was 75.8 %; 45 (8.4 %) participants without baseline brain metastases developed brain metastases during treatment. In an analysis restricted to patients with metastatic disease, outcomes with and without baseline brain metastases included: median PFS, 3.3 and 4.9 months (p < 0.005); 12-month PFS, 5 % and 16 %; median OS, 6.9 and 10.4 months (p < 0.005); and 12-month OS, 20 % and 44 %, respectively. CONCLUSION: These findings establish CNS progression rates with docetaxel in previously treated KRASmut advanced NSCLC and facilitate interpretation of data from ongoing randomized clinical trials of novel KRAS-targeted therapeutic strategies vs. docetaxel.

Retrospective observational cohort study on innovation in oncology and progress in survival: How far have we gotten in the two decades of treating patients with advanced non-small cell lung cancer as a single population?

We assessed the impact of new antineoplastic agents on the overall survival (OS) of advanced non-small cell lung cancer (aNSCLC) patients followed up until 2012. Multivariate regression models were run for OS (outcome) and four proxies for innovation (exposure): Index (InnovInd, for SEER-Research data 1973-2012) and three levels of aggregation of Mean Medication Vintage, i.e. Overall (MMVOverall), using data aggregated at the State Level (MMVState), and using patient-level data (MMVPatient) using data from the US captured in SEER-Medicare 1991-2012. We derived Hazard ratios (HR) from Royston-Parmar models and odds ratios (OR) from a logistic regression on 1-year OS. Including 164,704 patients (median age 72 years, 56.8% stage IV, 61.8% with no comorbidities, 37.8% with adenocarcinoma, 22.9% with squamous-cell, 6.1% were censored). One-year OS improved from 0.22 in 1973 to 0.39 in 2012, in correlation with InnovInd (r = 0.97). Ten new NSCLC drugs were approved and 28 more used off-label. Regression-models results indicate that therapeutic innovation only marginally reduced the risk of dying (HROverall = 0.98 [0.98-0.98], HRMMV-Patient = 0.98 [0.97-0.98], and HRMMV-State = 0.98 [0.98-0.98], and slightly improved 1-year survival (ORMMV-Overall = 1.05 95%CI [1.04-1.05]). These results were validated with data from the Swedish National Health Data registers. Until 2013, aNSCLC patients were treated undifferentiated and the introduction of innovative therapies had statistically significant, albeit modest, effects on survival. Most treatments used off-guidelines highlight the high unmet need; however new advancements in treatment may further improve survival.

Comparative effectiveness of nivolumab versus clinical practice for advanced gastric or gastroesophageal junction cancer.

Aim: To determine the effectiveness of nivolumab compared with routine clinical practice (RCP) for patients with gastric or gastroesophageal cancer refractory to, or intolerant of, two or more previous regimens, using real-world electronic patient records from a US population, a single-arm trial (CheckMate 032) and a randomized controlled trial in an Asian setting (ATTRACTION-2). Materials & methods: A simulated treatment comparison was conducted to predict overall survival for patients treated with nivolumab compared with RCP in the USA. Results: Results of the indirect simulated treatment comparison suggest that nivolumab is associated with a 50% reduction in the risk of all-cause mortality relative to RCP (Hazard ratio: 0.50; 95% CI: 0.36, 0.68). Conclusion: The survival benefit of nivolumab may extend more generally to the USA.

Treatment Patterns and Economic Burden by Lines of Therapy Among Patients with Advanced Hepatocellular Carcinoma Treated with Systemic Cancer Therapy.

PURPOSE: This study examined clinical and economic outcomes among patients with advanced hepatocellular carcinoma (HCC) treated with systemic agents by line of therapy. METHODS: Adults with ≥ 2 medical claims for primary diagnosed HCC (from January 1, 2008, through September 30, 2015) and ≥ 1 claim for systemic HCC-related therapy were identified in the IBM MarketScan® Research Databases. Continuous enrollment was required 6 months before and 1 month after diagnosis. Patients were categorized into first- (1L) and second-line (2L) treatment cohorts; those receiving sorafenib as 1L were evaluated. Treatment patterns, healthcare resource utilization, costs, and survival during 1L and 2L therapy were measured. Survival was assessed for patients linked to the Social Security Administration Master Death File. RESULTS: 1459 patients, 758 with death data, met the 1L cohort criteria; 163 patients, 87 with death data, later received 2L therapy. 77.1% had 1L sorafenib, alone or in combination. Median 1L treatment duration was 3.0 months; median survival time from start of 1L to death or censor was 6.8 months. There was no predominant 2L agent. Median 2L treatment duration was 3.0 months; median survival time from start of 2L was 9.3 months. Median total healthcare costs per patient per month were $13,297 for 1L (all), $13,471 for 1L (sorafenib), and $11,786 for 2L. CONCLUSIONS: Findings confirm high 1-year mortality for advanced HCC, suggesting a high cost burden. While no 2L therapy was available during this analysis, recently approved 2L agents have the potential to improve survival after sorafenib failure or intolerance.

Real-world treatment patterns, cost of care and effectiveness of therapies for patients with squamous cell carcinoma of head and neck pre and post approval of immuno-oncology agents.

Aims: In 2016, nivolumab and pembrolizumab were approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN) following progression after initial platinum-based therapy. We sought to explore the uptake, effectiveness, and impact on healthcare resource utilization (HRU) and total costs of care pre and post introduction of immuno-oncology (IO) agents.Materials and Methods: Recurrent/metastatic SCCHN patients were identified from a healthcare claims clearinghouse by selecting patients with a claim for distant metastases or who initiated systemic therapy at least 120 days following discontinuation of platinum-based therapy. Two cohorts were created according to the date of post-platinum therapy (PPT) initiation: pre-IO = 08/01/2014-07/31/2015; post-IO = 08/01/2016-07/31/2017. Treatment patterns and effectiveness (duration of treatment, time to next treatment) during first-line (1 L) PPT, HRU, and costs were compared between propensity-score matched patients from each cohort.Results: Of 716 patients identified (pre-IO = 265, post-IO = 451) 46.3% of post-IO patients received IO post-platinum. In 229 matched patients 20.0% of the post-IO compared to 10.7% of the pre-IO (p=.02) had at least a 6 month duration of 1 L PPT. Inpatient admissions during 1 L PPT: 34.1% post-IO versus 48.0% pre-IO (p= <.01). PPPM total costs of care in 1 L PPT were significantly greater post-IO ($11,535) compared to pre-IO ($9,054, p=.002). Time to next treatment (from 1 L PPT start) was 6.1 months pre-IO versus 7.4 months post-IO (p=.046).Limitations: Recurrent SCCHN patients were identified using a validated claims-based algorithm but misclassification may occur. Requiring patients to have received 1 L PPT the pre-IO cohort may be systematically different that the post-IO cohort as pre-IO patients were more likely to have not received further treatment beyond 1 L PPT.Conclusions: The significant uptake of IO therapy resulted in longer durations of therapy, lower rates of hospitalizations although higher treatment costs. The results suggest IO treatment provides additional clinical benefits to recurrent/metastatic SCCHN patients.

Survival, costs, and health care resource use by line of therapy in US Medicare patients with newly diagnosed glioblastoma: a retrospective observational study.

BACKGROUND: Glioblastoma (GBM) is associated with poor prognosis, large morbidity burden, and limited treatment options. This analysis evaluated real-world treatment patterns, overall survival, resource use, and costs among Medicare patients with GBM. METHODS: This retrospective observational study evaluated Medicare patients age 66 years or older with newly diagnosed GBM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2007 through 2013. Patients were followed from diagnosis to death or end of follow-up. An algorithm defined treatment patterns as lines of therapy (LOTs). The Kaplan-Meier method was used to estimate overall survival for the full sample as well as by LOT, surgical resection, Charlson Comorbidity Index (CCI), tumor size, and age. Resource use and costs during the follow-up period were reported in terms of total and per-patient-per-month (PPPM) estimates. RESULTS: A total of 4308 patients with GBM were identified (median age, 74 years; CCI of 0, 52%). The most commonly used first LOT was temozolomide (82%), whereas chemotherapy + bevacizumab was most prevalent for second-line (42%) and third-line (58%) therapy. The median overall survival was 5.9 months for resected patients and 3 months for unresected patients, with considerable heterogeneity depending on patient characteristics. A great proportion of patients had claims for an ICU admission (86.2%), skilled nursing facility (76.9%), and home health (56.0%) in the postdiagnosis period. The cumulative mean cost was $95 377 per patient and $18 053 PPPM, mostly attributed to hospitalizations. CONCLUSIONS: Limited treatment options, poor survival, and economic burden emphasize the need for novel interventions to improve care for Medicare patients with GBM.

Real-world Treatment Patterns and Clinical Outcomes Across Lines of Therapy in Patients With Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer.

BACKGROUND: First-line (1L) and second-line (2L) therapies for advanced/metastatic gastric cancer (GC) and gastroesophageal junction cancer (GEJC) have modest efficacy, and therapeutic options in subsequent lines are limited as disease progresses. We assessed real-world treatment patterns and outcomes for advanced/metastatic GC/GEJC. PATIENTS AND METHODS: Adult patients diagnosed with advanced/metastatic GC/GEJC between January 1, 2011 and April 30, 2018 were identified using the Flatiron Health database. Median overall survival (OS) from start of each line of therapy until death was estimated by the Kaplan-Meier method. Duration of therapy (DoT) was time from start date until end date of each line. RESULTS: We identified 3291 patients with advanced/metastatic GC/GEJC adenocarcinoma. At diagnosis, the median age was 68 years, 60% were white, 53% had initial stage IV disease, and 57% had GC. Of these 3291 patients, most (75%) received at least 1 therapy; 32% received 2L, 14% received third-line (3L) therapy, and 6% received at least 4 lines of therapy (4L+). The median OS from start of 1L was 10.7 months (2L, 7.6 months; 3L, 6.1 months; 4L+, 2.8 months). The median DoT in 1L was 2.2 months (2L, 2.1 months; 3L, 1.7 months; 4L+, 3.0 months). Use of targeted and immunotherapies generally increased progressively with each subsequent line of therapy. CONCLUSION: One-quarter of patients with advanced/metastatic GC/GEJC remained untreated, and only approximately one-half of patients receiving 1L therapy received subsequent treatment. In all lines of therapy, OS was generally poor and DoT was short. More effective treatment options are needed across all lines of therapy for this highly burdensome disease.

Comparative effectiveness of nivolumab versus standard of care for third-line patients with small-cell lung cancer.

Aim: To estimate the comparative effectiveness of nivolumab versus standard of care (SOC) in terms of overall survival (OS) for small-cell lung cancer patients treated with two prior lines of chemotherapy, in other words, third line in the USA. Materials & methods: Data were from CheckMate 032, a single-arm trial of nivolumab, and real-world electronic patient records. Comparisons of OS were conducted using three different methods to adjust for differences (regression, weighting and doubly robust) between the populations. Results: Nivolumab was associated with longer survival compared with SOC (hazard ratio for OS: 0.58-0.70) across all methods for adjustment. Conclusion: Nivolumab was more efficacious in terms of OS as third-line treatment for small-cell lung cancer compared with current SOC in the USA.

Cost-effectiveness analysis of nivolumab for the treatment of squamous cell carcinoma of the head and neck in the United States.

Aim: To assess the cost-effectiveness of nivolumab monotherapy for recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) in the US.Methods: We constructed a cohort-based partitioned survival model for three health states (progression-free, progressed disease, and death). Using overall survival and progression-free survival data from the nivolumab and investigator's choice (IC) arms of the CheckMate 141 study, the proportion of patients in each health state was estimated by parametric modeling over a 25-year period. Cost, utility, adverse event, and disease management data inputs were obtained from relevant literature and applied to patients in each health state. A scenario analysis was conducted assuming increased uptake of subsequent immunotherapies. A one-way deterministic sensitivity analysis assessed the impact of variation in multiple parameters. A probabilistic sensitivity analysis in which probabilistic distributions were applied to each input during 1,000 model iterations was also conducted.Results: Total costs incurred were higher with nivolumab ($101,552) than with IC ($38,067). Nivolumab was associated with a higher number of life-years (LY; 1.21) and quality-adjusted life-years (QALYs; 0.89), compared with IC (0.68 and 0.42, respectively). The incremental cost-effectiveness ratio for nivolumab compared with IC was $134,438 per QALY, and this remained qualitatively similar when increased uptake of subsequent immunotherapies was assumed ($129,603 per QALY). Sensitivity analyses supported these findings.Conclusions: These results suggest that, at a willingness-to-pay threshold of $150,000 per QALY, nivolumab is a cost-effective option for therapy of SCCHN in the US.

A Real-World Claims Analysis of Costs and Patterns of Care in Treated Patients with Glioblastoma Multiforme in the United States.

BACKGROUND: Patients with glioblastoma multiforme (GBM) have a poor prognosis and high likelihood of recurrence. Routine care for incident cases in the United States involves surgical resection, followed by radiation therapy (RT) with concurrent and adjuvant temozolomide. Real-world data reporting the treatments and health care burden associated with GBM are limited. OBJECTIVE: To assess patterns of care, health care resource utilization (HCRU), and costs associated with treatment of GBM in the United States. METHODS: This study is a retrospective claims database analysis. Adult patients with a GBM diagnosis (index date) between January 1, 2010, and June 30, 2016, who had undergone brain surgery within 90 days of the index date, had received temozolomide and/or RT up to 90 days after index date, and had at least 6 months of continuous enrollment before the index date, were identified. Patients were excluded if they had (a) another primary cancer within 6 months pre-index, (b) secondary brain metastases, or (c) received temozolomide and/or RT pre-index. Baseline characteristics, treatments, HCRU, and costs were reported. First-line therapy began upon first receipt of RT and/or temozolomide after index date; second-line therapy began when a new drug was added > 28 days after initiation of first-line therapy or when there was a treatment gap > 90 days. Treatment regimens, duration of treatment (corrected group prognosis method), HCRU, and costs were reported descriptively in the 0- to 6-month and 7- to 12-month periods following initiation of first-line and second-line therapy. RESULTS: Baseline characteristics were comparable between patients receiving temozolomide and/or RT. Patients receiving RT without chemotherapy tended to be older, be retired, and have more baseline comorbidities. Of the 4,071 patients receiving first-line therapy for GBM, most (73.0%) received temozolomide + RT; 24.4% received RT; and 2.5% received temozolomide monotherapy. Of those receiving first-line therapy, 1,283 (31.5%) patients subsequently received second-line therapy: 39.4% received bevacizumab monotherapy; 28.9% received bevacizumab combination therapy (temozolomide, 45.2% of patients; irinotecan, 24.3%; and temozolomide + lomustine, 15.4%); 15.5% received temozolomide monotherapy; and 13.7% received other systemic cancer therapies. The proportion of patients with hospitalizations increased from 2.9% (4-6 months pre-index) to 20.8% in the 3 months before the index date (likely due to diagnostic procedures) and 28.1% in the first 6 months after index (likely due to surgery) and then decreased to 13.3% in the 7- to 12-month period after index. Mean total per-patient costs at 6 and 12 months were $117,325 and $162,550 (first line) and $126,128 and $243,833 (second line). Costs in all time periods were largely driven by costs of RT/systemic cancer therapy. CONCLUSIONS: Most patients with newly diagnosed GBM received treatment according to recommendations. However, relatively few patients received second-line therapy, and the HCRU burden and costs associated with both lines of therapy were substantial. Novel therapies for GBM are required to improve treatment options and outcomes in these patients. DISCLOSURES: This study was funded by Bristol-Myers Squibb (Princeton Pike, NJ). Neither honoraria nor payments were provided for authorship. Norden received consultancy fees relating to this study from Bristol-Myers Squibb. Dastani, Korytowsky, Le, Singh, and You are employees of Bristol-Myers Squibb. Dastani and Korytowsky are shareholders of Bristol-Myers Squibb. Bobiak was an employee of Bristol-Myers Squibb at the time of this study. Preliminary data from this study were previously presented at the International Society for Pharmacoeconomics and Outcomes Research 22nd Annual International Meeting in Boston, MA, May 20-24, 2017.

Real-World Clinical Impact of Immune Checkpoint Inhibitors in Patients With Advanced/Metastatic Non-Small Cell Lung Cancer After Platinum Chemotherapy.

BACKGROUND: The real-world effect of anti-programmed death ligand 1 (PD-L1) therapies is unclear. We compared US patients who received second-line therapy for non-small-cell lung cancer (NSCLC) before and shortly after US Food and Drug Administration (FDA) approval of PD-L1 inhibitors. PATIENTS AND METHODS: Patients in the Flatiron Health database (≥18 years; received first-line platinum therapy for advanced/metastatic NSCLC; ≥6 months of follow-up) were assessed before ("historical": January 1, 2011 to December 31, 2013) and after ("current": January 1, 2015 to May 31, 2017) FDA approval of anti-PD-L1 therapies for NSCLC. Index was start of second-line therapy. Baseline variables, treatment patterns, and overall survival (OS) were reported. RESULTS: A greater proportion of patients in the current cohort received second-line treatment than in the historical cohort (n = 4240 [57.0%] vs. n = 2357 [37.4%]); 48.8% [n = 2071] of the current second-line patients received anti-PD-L1 therapy. Current patients were more likely to receive second-line anti-PD-L1 therapy if they had poorer Eastern Cooperative Oncology Group (ECOG) performance status (≥2), had squamous histology, or had no epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or ROS proto-oncogene 1 mutations. Median OS from index was higher in the current cohort (9.4 [95% confidence interval (CI), 8.9-9.9] months) than the historical cohort (7.3 [95% CI, 6.9-7.8] months). Adjusted for sex, race, ECOG performance status, disease stage, and Kirsten rat sarcoma viral oncogene homolog, EGFR, and ALK status, OS was improved by 15% in the current cohort. CONCLUSION: Contemporary patients are more likely to receive second-line therapy and have longer OS than patients who received care before approval of anti-PD-L1 therapies.

Immunotargeted therapy in melanoma: patient, provider preferences, and willingness to pay at an academic cancer center.

New melanoma therapies have shifted the expectations of patients and providers. Evaluating the impact of treatment characteristics may enhance shared decision making. A survey, including a discrete choice experiment, was utilized to evaluate perceived trade-offs of different melanoma treatments and to estimate out-of-pocket (OOP) willingness-to-pay (WTP) thresholds (January 2016 to March 2016). Participants included patients with melanoma at Huntsman Cancer Institute and their cancer care providers. Stakeholder focus groups were conducted to identify treatment attributes. Descriptive and comparative statistics and multinomial logit model were used to evaluate responses. Response rates were 41.9% (N = 220) for patients and 37.7% (N = 20) for providers. Immunotherapy and targeted therapy attributes considered important by participants were overall survival, immunotherapy-related side effects, and skin toxicities. Patients and providers had significantly different views of quality-of-life expectations, anxiety toward melanoma, trust to make treatment decisions, sharing concerns about treatment, time to discuss treatment, understanding OOP costs, and willingness to undergo/recommend treatment (half of the patients would undergo treatment if it was effective for > 24 months). Among patients, the average monthly OOP WTP for combination immunotherapy with nivolumab + ipilimumab was $ 2357 and for BRAF/MEK inhibitor was $1648. Among providers, these estimates were $ 2484 and $1350, respectively. Discordance existed between patients' and providers' perceptions about quality of life expectations, degree of anxiety, sharing of opinions, and progression-free survival. Our study suggests that patients and providers exhibit a higher OOP WTP for combination immunotherapy treatment compared with BRAF/MEK inhibitors, influenced predominately by overall survival expectations.

Indirect comparison of nivolumab ± ipilimumab (CheckMate 032) versus other treatments for recurrent small-cell lung cancer.

Aim: To estimate the comparative efficacy of nivolumab ± ipilimumab versus alternative treatments for small-cell lung cancer after at least one prior line of chemotherapy. Materials & methods: A systematic literature review identified six randomized controlled trials (RCTs) that could be connected in a network. The Kaplan-Meier survival curves from these RCTs were synthesized using network meta-analysis models. Aggregate-level matching was used to connect CheckMate 032 to the RCTs. Results: CheckMate 032 was connected to the network by Amrubicin Clinical Trial-1. Nivolumab ± ipilimumab had a more durable tumor response and more favorable long-term survival versus topotecan via intravenous and versus amrubicin. Conclusion: Compared with chemotherapies for recurrent small-cell lung cancer, nivolumab ± ipilimumab improves response duration, which may translate to long-term survival benefits.

Tumor mutational burden in lung cancer: a systematic literature review.

Purpose: To assess the association of tumor mutational burden (TMB) with clinical outcomes, other biomarkers and patient/disease characteristics in patients receiving therapy for lung cancer. Results: In total, 4,303 publications were identified; 81 publications were included. The majority of publications assessing clinical efficacy of immunotherapy reported an association with high TMB, particularly when assessing progression-free survival and objective response rate. High TMB was consistently associated with TP53 alterations, and negatively associated with EGFR mutations. High TMB was also associated with smoking, squamous cell non-small cell lung carcinoma, and being male. Methods: A systematic literature review based upon an a priori protocol was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane methodologies. Searches were conducted in EMBASE, SCOPUS, Ovid MEDLINE®, and Emcare (from January 2012 until April 2018) and in two clinical trial registries. Conference abstracts were identified in EMBASE, and in targeted searches of recent major conference proceedings (from January 2016 until April 2018). Publications reporting data in patients receiving therapy for lung cancer that reported TMB and its association with clinical efficacy, or with other biomarkers or patient/disease characteristics, were included. Results are presented descriptively. Conclusion: This systematic literature review identified several clinical outcomes, biomarkers, and patient/disease characteristics associated with high TMB, and highlights the need for standardized definitions and testing practices. Further studies using standardized methodology are required to inform treatment decisions.