Treatment patterns and outcomes in patients with metastatic synovial sarcoma in France, Germany, Italy, Spain and the UK.

Aim: Describing the treatment patterns, outcomes by line of treatment (LOT), and healthcare resource utilization (HCRU) in patients with metastatic synovial sarcoma (mSS). Patients & methods: In this descriptive, non-interventional, retrospective cohort study, physicians from five European countries reported on patients with recent pharmacological treatment for mSS. Results: Among 296 patients with mSS, 86.1, 38.9 and 8.4% received 1 LOT (1L), 2 LOTs (2L) and 3+ LOTs (L3+), respectively. Common regimens were doxorubicin/ifosfamide-based (37.4%) for 1L and trabectedin-based for 2L (29.7%). For 1L, median time to next treatment was 13.1 and 6.0 months for living and deceased patients, respectively. Median OS was 22.0, 6.0 and 4.9 months in all patients, 2L and 3L, respectively. HCRU data showed median one inpatient hospital admission, 3 days in hospital and four outpatient visits yearly. Conclusion: This large-scale study documents high unmet needs in patients previously treated for mSS and for more effective therapies.

Treatment patterns and outcomes in metastatic synovial sarcoma: a real-world study in the US oncology network.

Aim: To examine and understand patient characteristics, treatment patterns and outcomes for patients with metastatic synovial sarcoma (mSS) treated in a US community setting. Materials & methods: Retrospective observational study in adults with mSS in The US Oncology Network (diagnosed January 2012-December 2018). Results: Of 202 patients diagnosed with synovial sarcoma (SS), 71 had mSS. Of 39 patients with mSS who received first-line (1L) systemic treatment, 25 and 16 continued to 2L and 3L+ treatment, respectively. With each subsequent treatment line, time-to-treatment-discontinuation (1L-3L: 3.9-2.7 months) and time-to-next-treatment (1L-3L: 9.3-4.6 months) decreased. At 1L, median overall survival was 24.5 months. Conclusion: This study highlights the ongoing need for effective therapies for mSS.

Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma (STS), a group of rare cancers that start in the soft tissues, such as muscle, tendons, fat, lymph and blood vessels and nerves. Usually STS presents in one location, and frequently spreads to other locations, referred to as metastatic SS (mSS). Many studies have explored the characteristics, treatments and outcomes of people with STS. Yet, a limited number of studies have been performed specifically for people with mSS. This study aims to describe characteristics, treatment patterns and clinical outcomes of people with mSS treated in a US community setting. The study showed that more than a third of people diagnosed with SS had disease that spread, mostly to the lung. Of the 71 people with mSS included in the analysis, 39 people received chemotherapy. Of these, 25 people with mSS needed second-line chemotherapy and a further 16 people with mSS required third-line treatment. People with mSS who did not respond well to chemotherapy received a variability of treatments in the US community setting. More lines of treatment were associated with shorter time-to-next-treatment and reduced survival time. Together, these findings highlight the burden of illness and the need for more effective treatments for people with this rare disease. Investigating the characteristics, treatment patterns and clinical outcomes of people with mSS can help to understand the unmet need in this population and pave the way to improving future treatment approaches.

Qualitative study to characterize patient experience and relevance of patient-reported outcome measures for patients with metastatic synovial sarcoma.

BACKGROUND: The outlook for patients with metastatic synovial sarcoma (mSS) is poor. Better understanding of patient experience in this setting, beyond clinical measures, may guide improvements in management. Validated patient-reported outcome (PRO) instruments specific to many types of cancer exist, but for rare cancers this is often not the case. METHODS: This study aimed to characterize patient experiences of symptoms and impacts of mSS and evaluate the content validity and relevance of the novel European Organization for Research and Treatment of Cancer Item Library 31 (EORTC IL31) Disease Symptoms PRO tool assessing synovial sarcoma symptoms. This tool comprises items from preexisting, validated cancer-specific PRO instruments from the EORTC Item Library. It was developed as an mSS-specific add-on to the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30), which evaluates general cancer and treatment-related symptoms and functioning. This was a non-interventional, qualitative interview study involving semi-structured, concept elicitation (CE) and cognitive debriefing (CD) telephone interviews in adults with mSS. CE explored symptoms and their impact on functioning and quality of life; CD assessed participant understanding and relevance of the PRO tools. RESULTS: Among the 8 participants, the most common disease-related symptoms reported during CE were fatigue and pain, while shortness of breath was one of the most bothersome. The greatest negative impacts of mSS occurred in domains of physical functioning and sleep. Key treatment priorities for patients were to improve disrupted sleep and ability to undertake strenuous activities. CONCLUSIONS: The interviews showed that, when used together, the EORTC IL31 and EORTC QLQ-C30 covered symptoms and impacts of most relevance and importance to patients with mSS, with no notable gaps and good conceptual coverage. This study therefore supports the content validity of 2 tools in mSS, advocating their use in clinical trials to assess treatment impact on PRO measures of importance to these patients.

Real-world treatment patterns and survival of patients with BRAF V600-mutated metastatic non-small cell lung cancer.

INTRODUCTION: Clinical outcomes data on BRAF-mutated non-small cell lung cancer (NSCLC) patients treated in routine practice is limited. To address this gap, we described treatment patterns and survival in a cohort of these patients evaluated/treated at 7 US academic cancer centers during 2009-2016. METHODS: This was a retrospective chart review. Patients with BRAF V600-mutated metastatic NSCLC were selected. Current/previous participants in BRAF-related trials were excluded. Onset of metastatic NSCLC defined a patient's index date, which had to occur ≥6 months before the chart review date. Analyses were descriptive, including Kaplan-Meier analyses for overall survival (OS). RESULTS: The study included 72 patients. At index, median age (range) was 65 (44-90) years; 61.1% were female. Fifty-two patients received ≥1 line of systemic therapy for metastatic disease. Platinum-based doublet chemotherapy was the most common first-line (1 L) regimen (76.9% of 1 l recipients); no patient received 1 l targeted therapy (TT) with a BRAF/MEK inhibitor. In total, 20 patients received TT in any treatment line (2 l or later). At time of review, 38 patients were deceased. Median (95%CI) OS from index for all patients was 31.0 (14.5, 63.8) months. Median (95%CI) OS was 56.5 (13.4, 89.1) months from index for TT recipients and 27.2 (10.6, 64.6) months in patients not treated with TT. CONCLUSION: Survival time in BRAF V600-mutated metastatic NSCLC patients studied here was higher than expected based on indirect comparisons with historical NSCLC cohorts for whom no oncogenic driver (BRAF or otherwise) was present. TT recipients had a numerically longer OS from metastatic onset than patients receiving usual care, further highlighting the importance of TT in BRAF V600-mutant NSCLC.

Cost-effectiveness of ceritinib in previously untreated anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer in the United States.

AIMS: To assess the cost-effectiveness of first-line ceritinib vs crizotinib and platinum doublet chemotherapy for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) from a US third-party payer's perspective. MATERIALS AND METHODS: A partitioned survival model with three health states (stable disease, progressive disease, death) was developed over a 20-year time horizon. Ceritinib's efficacy inputs (progression-free and overall survival) were estimated from ASCEND-4; parametric survival models extrapolated data beyond the trial period. The relative efficacy of ceritinib vs chemotherapy was obtained from ASCEND-4, the relative efficacy of ceritinib vs crizotinib was estimated using a matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014. Drug acquisition, treatment administration, adverse event management, and medical costs were obtained from publicly available databases and the literature, and inflated to 2016 US dollars. Treatment-specific stable-state utilities were derived from trials and progressive-state utility from the literature. Incremental costs per quality-adjusted life year (QALY) were estimated for ceritinib vs each comparator. Cost-effectiveness was assessed based on US willingness-to-pay thresholds. Deterministic and probabilistic sensitivity analyses were performed to test model robustness. RESULTS: In the base case, first-line ceritinib was associated with total direct costs of $299,777 and 3.28 QALYs (from 4.61 life years gained [LYG]) over 20 years. First-line crizotinib and chemotherapy were associated with 2.73 and 2.41 QALYs, 3.92 and 3.53 LYG, and $263,172 and $228,184 total direct costs, respectively. The incremental cost per QALY gained was $66,064 for ceritinib vs crizotinib and $81,645 for ceritinib vs chemotherapy. In the first 2 years following treatment initiation, ceritinib dominated crizotinib by conferring greater health benefits at reduced total costs. Results were robust to deterministic and probabilistic sensitivity analyses. LIMITATIONS: In the absence of head-to-head trials, an indirect comparison method was used. CONCLUSIONS: Ceritinib is cost-effective compared to crizotinib and chemotherapy in the treatment of previously untreated ALK-positive metastatic NCSLC in the US.

Prognostic factors for survival following initiation of second-line treatment with everolimus for metastatic renal cell carcinoma: evidence from a nationwide sample of clinical practice in the United States.

OBJECTIVE: Comparing prognostic factors for overall survival (OS) in community-practice metastatic renal cell carcinoma (mRCC) patients receiving second-line everolimus with those previously reported in clinical trials. RESEARCH DESIGN AND METHODS: Two separate chart sets (2009 - 2012) were used to develop and validate a prognostic model for patients initiating second-line everolimus after first-line tyrosine kinase inhibitor (TKI). MAIN OUTCOME MEASURES: Prognostic factors for OS have been identified and validated in separate samples. RESULTS: One-year OS probabilities in the study (n = 220) and validation (n = 97) samples were 68 and 67%; median OS was 19 and 23 months - higher than the 1-year OS of 60% and median OS of 14.8 months of RECORD-1. Karnofsky performance score < 80%, duration of mRCC < 1 year, progression on first-line TKI, liver metastasis and clear cell histology were significant prognostic factors for shorter survival. One-year OS estimates were 84% for validation sample patients with 0 - 2 risk factors, 63% for 3 risk factors and 22% for 4 - 5 risk factors (log-rank p < 0.001). CONCLUSION: Real-world prognostic factors for OS following second-line everolimus for mRCC were largely consistent with those previously identified in trial data; however, OS was longer in the practice setting than in clinical trials and was not associated with type of first-line TKI.

Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: synthesis of findings from two multi-practice chart reviews in the United States.

BACKGROUND: Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study compares the effectiveness of these therapies in a multi-practice chart review and synthesizes the findings with those of a similarly designed study. METHODS: Medical oncologists/hematologists (N = 36) were recruited to review charts for patients aged ≥18 years, received a first-line TKI and initiated second-line targeted therapy in 2010 or later. The primary outcome was time from second-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving second-line everolimus (EVE), temsirolimus (TEM), or TKI as a class, using a Cox proportional hazards model adjusting for type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled, in a meta-analysis, with previously reported HRs for progression-free survival from a chart review with a similar design. RESULTS: A total of 138, 64 and 79 patients received second-line therapy with EVE, TEM or a TKI, respectively. Adjusting for baseline characteristics, EVE was associated with numerical, but not statistically significant, reductions of 28% (HR = 0.72; 95% CI [0.45-1.16]) and 26% (HR = 0.74; 95% CI [0.48-1.15]) in the hazard of TTF compared to TEM and TKI, respectively. After pooling the HRs from both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (HR = 0.73; 95% CI [0.57-0.93]; and HR = 0.75; 95% CI [0.57-0.98], respectively). LIMITATIONS: LIMITATIONS include retrospective analyses with possible missing or erroneous chart data, confounding of unobserved factors due to non-randomization, and limited data for axitinib during the study period. CONCLUSIONS: In pooled results from two independent multi-practice chart reviews of second-line mRCC treatment, EVE was associated with significantly reduced hazards of treatment failure compared to TEM and to TKIs as a class.

Treatment patterns in metastatic renal cell carcinoma: a retrospective review of medical records from US community oncology practices.

BACKGROUND: Vascular endothelial growth factor (VEGF) inhibitors, including targeted therapy with tyrosine kinase inhibitors (TKIs) and the angiogenesis inhibitor bevacizumab, and mammalian target of rapamycin (mTOR) inhibitors are now the standard of care for metastatic renal cell carcinoma (mRCC). However, real-world treatment patterns are not well characterized. OBJECTIVE: To describe treatment patterns during the first, second, and third lines of targeted therapies for mRCC among community oncologists in the US. METHODS: Participating physicians recruited from a nationwide panel each identified up to 15 adult mRCC patients who initiated a second therapy after January 2010. Information extracted from medical records included types of targeted therapies, reasons for treatment choices, patterns of treatment discontinuation, and dose adjustments. RESULTS: Thirty-six physicians contributed charts from 433 mRCC patients. Seventy-seven percent of patients received a VEGF inhibitor as first targeted therapy; 23% received an mTOR inhibitor. Among first-line VEGF users, second-line treatments were 66% mTOR and 34% VEGF inhibitors. Among first-line mTOR users, second-line treatments were 94% VEGF and 6% mTOR inhibitors. Sunitinib followed by everolimus was the most commonly used treatment sequence. Estimated median duration for second targeted therapy was 8.6 months, and median overall survival (OS) and progression-free survival (PFS) were 27.4 and 10.8 months, respectively. Efficacy, treatment guidelines and mechanism of action were the most important considerations for treatment choice. LIMITATIONS: LIMITATIONS include no adjustment for baseline characteristics, possible difference between physician-defined progression and central review in the clinical trial setting, and limited data availability for axitinib during the study period. CONCLUSION: In this large retrospective chart review among community oncologists, VEGF-mTOR-VEGF was the most common treatment sequence for mRCC. The most common drugs were sunitinib in the first line and everolimus in the second line.