Development and validation of algorithms for identifying lines of therapy in multiple myeloma using real-world data.

Aim: To validate algorithms based on electronic health data to identify composition of lines of therapy (LOT) in multiple myeloma (MM). Materials & methods: This study used available electronic health data for selected adults within Henry Ford Health (Michigan, USA) newly diagnosed with MM in 2006-2017. Algorithm performance in this population was verified via chart review. As with prior oncology studies, good performance was defined as positive predictive value (PPV) ≥75%. Results: Accuracy for identifying LOT1 (N = 133) was 85.0%. For the most frequent regimens, accuracy was 92.5-97.7%, PPV 80.6-93.8%, sensitivity 88.2-89.3% and specificity 94.3-99.1%. Algorithm performance decreased in subsequent LOTs, with decreasing sample sizes. Only 19.5% of patients received maintenance therapy during LOT1. Accuracy for identifying maintenance therapy was 85.7%; PPV for the most common maintenance therapy was 73.3%. Conclusion: Algorithms performed well in identifying LOT1 - especially more commonly used regimens - and slightly less well in identifying maintenance therapy therein.

Electronic health data helps us understand treatment in the 'real world'. The data has great value in cancer if we can identify the drugs patients get. Yet this is hard in multiple myeloma (MM), where treatment is complex. Algorithms (set of decision rules) to identify drugs can help here. We tested an existing algorithm for identifying 'lines of therapy' (LOT) given to patients with MM. Each LOT included one or more drugs for MM. We also developed and tested a new algorithm for 'maintenance therapy'. This is a treatment given to help maintain the response to the main MM treatment. We tested how well the algorithms identified MM treatments in electronic health data. This data came from Henry Ford Health, a healthcare system in Michigan, USA. Treatments were confirmed by cancer specialists who reviewed medical charts. The LOT algorithm was good at finding the first LOT patients. The maintenance algorithm did a fair job of identifying the most used therapy. Our algorithms could help researchers study the real-world treatment of MM.

Clinical management of metastatic hormone receptor-positive, HER2-negative breast cancer (MBC) after CDK 4/6 inhibitors: a retrospective single-institution study.

PURPOSE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), in combination with endocrine therapy (ET), are standard either in the first (1L) or second-line (2L) setting for the treatment of hormone receptor (HR) positive, HER2-negative metastatic breast cancer (MBC). However, the optimal sequencing of treatments after progression on CDK4/6i remains unknown. We performed a single-institution analysis to identify treatments and outcomes after progression on a CDK4/6i. METHODS: We identified patients with HR-positive, HER2-negative MBC prescribed a CDK4/6i in the 1L or 2L settings from December 2014 to February 2018 at Mayo Clinic in Rochester, Minnesota. Outcomes were collected through September 30, 2020. RESULTS: Palbociclib, in combination with letrozole or fulvestrant, was the most prescribed CDK4/6i. The 1L and 2L CDK4/6i cohorts exhibited comparable overall survival (OS), but progression-free survival (PFS) was longer in the 1L than the 2L cohort [28.2 months (95% CI 19.6-34.9) vs 19.8 months (95% CI 15.7-29.6)]. The most common post-CDK4/6i treatments were PI3K/mTOR inhibitors (PI3K/mTORi), single-agent ET, or chemotherapy. PFS in the 1L CDK4/6i cohort following PI3K/mTORi was 8.5 months (95% CI 5.5 months-NE), single-agent ET was 6.0 months (95% CI 3.3-14.0 months), and chemotherapy PFS was 5.4 months (95% CI 3.3 months-NE). CONCLUSIONS: Following progression on a CDK 4/6i, mPFS was short, with similar PFS times comparing chemotherapy and ET, with slightly longer PFS for targeted strategies (PI3K/mTOR). These results highlight a major need to better understand the mechanisms of CDK4/6i resistance and identify new therapeutic strategies for these patients.

Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016. / Consenso para el tratamiento de la esclerosis múltiple 2016. Sociedad Española de Neurología.

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease. The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations. This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs.

Concepts of lines of therapy in cancer treatment: findings from an expert interview-based study.

OBJECTIVE: The concept of lines of therapy (LOT) in cancer treatment is often considered for decision making in tumor boards and clinical management, but lacks a common definition across medical specialties. The complexity and heterogeneity of malignancies and treatment modalities contribute to an inconsistent understanding of LOT among physicians. This study assesses the heterogeneity of understandings of the LOT concept, its major dimensions, and criteria from the perspective of physicians of different specialties with an oncological focus in Germany. Semi-structured expert interviews with nine physicians were conducted and evaluated using qualitative content analysis. RESULTS: Most interviewees agreed that there is no single definition for LOT and found it difficult to explicate their understanding. A majority of experts stated that they had already encountered misunderstandings with colleagues regarding LOT and that they had problems with deciphering LOT from the medical records of their patients. Disagreement emerged about the roles of the following within the LOT concept: maintenance therapy, treatment intention, different therapy modalities, changing pharmaceutical agents, and therapy breaks. Respondents predominantly considered the same criteria as decisive for the definition of LOT as for a change in LOT (e.g., the occurrence of a progression event or tumor recurrence).

Consensus Statement on medication use in multiple sclerosis by the Spanish Society of Neurology's study group for demyelinating diseases.

Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment.

Understanding Real-World Treatment Patterns and Clinical Outcomes among Metastatic Melanoma Patients in Alberta, Canada.

Immunotherapy and targeted therapies have been shown to considerably improve long-term survival outcomes in metastatic melanoma patients. Real-world evidence on the uptake of novel therapies and outcomes for this patient population in Canada are limited. We conducted a population-based retrospective cohort study of all metastatic melanoma patients diagnosed in Alberta, Canada (2015-2018) using electronic medical records and administrative data. Information on BRAF testing for patients diagnosed in 2017 or 2018 was obtained through chart abstraction. In total, 434 metastatic melanoma patients were included, of which 110 (25.3%) were de novo metastatic cases. The median age at diagnosis was 66 years (IQR: 57-76) and 70.0% were men. BRAF testing was completed for the majority of patients (88.7%). Among all patients, 60.4%, 19.1%, and 6.0% initiated first-line, second-line, and third-line systemic therapy. The most common therapies were anti-PD-1 and targeted therapies. The two-year survival probability from first-line therapy, second-line therapy, and third-line therapy was 0.50 (95% CI: 0.44-0.57), 0.26 (95% CI: 0.17-0.40), and 0.14 (95% CI: 0.40-0.46), respectively. In the first-line setting, survival was highest for patients that received ipilimumab or ipilimumab plus nivolumab, while targeted therapy had the highest survival in the second-line setting. This study indicates that novel therapies improve survival in the real world but a considerable proportion of patients do not receive treatment with systemic therapy.

Real-world treatment patterns for patients with newly diagnosed multiple myeloma in Alberta, Canada.

The purpose of this study is to describe the real-world multiple myeloma (MM) population in Alberta by examining patient/clinical characteristics and the treatment landscape. A retrospective, observational study was conducted using province-wide, administrative health data from Alberta, Canada evaluating newly diagnosed MM (NDMM) patients. Between 1 April 2011 and 31 March 2017, 1377 treated NDMM cases were identified. Of those, 328 (23.8%) received an autologous stem cell transplant (ASCT) within the first year of diagnosis. In the ASCT group, 189 advanced to second-line (57.6%), 103 (32.6%) to third-line and 97 (29.5%) had four or more lines of therapy. In non-ASCT patients, 553 (52.7%) advanced to second-line, 238 (22.7%) to third-line, and 154 (14.7%) had 4 or more lines of therapy. We observed a significant treatment attrition rate in NDMM. Therefore, the use of best therapy upfront and novel strategies aiming to decrease attrition rates in MM is encouraged.

Real-World Time on Treatment with First-Line Pembrolizumab Monotherapy for Advanced NSCLC with PD-L1 Expression ≥ 50%: 3-Year Follow-Up Data.

Our aim was to evaluate real-world time on treatment (rwToT), overall and by KRAS mutation status, with first-line pembrolizumab monotherapy for advanced non-small cell lung cancer (NSCLC) in real-world oncology practice in the US. rwToT is a readily available, intermediate-range endpoint that is moderately to highly correlated with overall survival in clinical trials and real-world data. Using deidentified electronic medical record data, we studied patients with ECOG performance status (PS) of 0-2 who initiated pembrolizumab (1 November 2016 to 31 March 2020) for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% and without EGFR/ALK/ROS1 genomic alterations. The data cutoff was 31 March 2021, and the median study follow-up was 34 months. The Kaplan-Meier median rwToT with first-line pembrolizumab monotherapy was 7.4 months (95% CI, 6.3-8.1) for 807 patients with PS 0-1, which was consistent with the median treatment duration in the KEYNOTE-024 trial (7.9 months). The median rwToT for 237 patients with PS 2 was 2.1 months (95% CI, 1.4-2.8). For those with KRAS-mutated and KRAS wild-type nonsquamous NSCLC and PS 0-1, the median rwToT was 7.6 months and 7.0 months, respectively. Our findings suggest long-term benefit of first-line pembrolizumab monotherapy for advanced NSCLC with PD-L1 expression ≥ 50% in real-world settings in the US, particularly for patients with good performance status at the start of therapy, irrespective of KRAS status.

Pathological complete remission in ALK-positive lung cancer patient after multiple lines of conversion therapy.

Introduction: Traditional therapeutic approaches for the treatment of advanced non-small-cell lung cancer (NSCLC) are based on chemotherapy. However, the discovery and understanding of oncogenic driver alterations has led to the development of targeted therapies that have substantially improved patient outcomes. Still, to date, there have been no reports of patients with advanced anaplastic lymphoma kinase (ALK)-positive lung cancer achieving clinical complete response (cCR) in the systemic lesion and pathological complete remission (pCR) in primary lung lesion after multiple lines of conversion therapy. Methods: In this case, a 55-year-old man was diagnosed with ALK-positive, stage IV lung adenocarcinoma using immunohistochemistry and next generation sequencing (NGS) tests. Results: Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and alectinib, were used respectively as first-line, second-line, and third-line therapy. The patient received treatment with crizotinib and achieved partial response (PR), but 5 months later the efficacy was evaluated as progressive disease (PD). Ceritinib was used as the second-line treatment, but the disease progressed 6 months later. Alectinib was used as the third-line treatment, but the efficacy was evaluated as PD. From April 2019 to November 2019, the patient received 4 cycles of induction chemotherapy with pemetrexed/carboplatin/bevacizumab and then switched to pemetrexed/bevacizumab as the fourth-line treatment, and received the fifth line treatment, cetuximab/paclitaxel liposome/nedaplatin, for 1 cycle, but the disease still progressed. Then the patient received the sixth line of treatment, camrelizumab/lorlatinib, for 9 antitumor cycles, resulting in PR. The patient underwent surgery followed by maintenance treatment with lorlatinib and achieved cCR. To our knowledge, this is the first documented case of cCR in a patient with ALK-positive advanced lung adenocarcinoma treated with multiple lines of therapy followed by surgical treatment. Discussion: This case reveals the possible survival benefit of immunotherapy after multiple line treatment in ALK-positive advanced lung adenocarcinoma, indicating that it is possible find new therapeutic targets based on NGS molecular detection and provide precise therapeutic strategies for clinical practice when drug resistance or progression occurs in cancer therapy.

Real-World Treatment Patterns and Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in the US Prior to PARP Inhibitors.

INTRODUCTION: Therapeutic options for metastatic castration-resistant prostate cancer (mCRPC) patients are continuously advancing. We described mCRPC treatment patterns in the US from 2013 to 2019. METHODS: Patients with a confirmed mCRPC diagnosis and adenocarcinoma histology were included in the US Flatiron Health Electronic Health Record-derived de-identified database. Treatment patterns [including treatment per lines of therapies (LOTs), LOT sequences, and time on treatment] and overall survival (OS) have been described in mCRPC settings. RESULTS: Of 5213 patients (mean age: 72.6 years), 4374 (83.9%) were treated with ≥ 1 LOT post-mCRPC diagnosis (among those with ≥ 1 LOT, 55.3%, 29.5%, 14.7%, and 6.7% had ≥ 2, 3, 4, and 5 LOTs, respectively). In first line (1L), the main treatment class was next-generation hormonal agents (NHA; 62.5% of patients with ≥ 1 LOT), while the shortest and longest time on 1L were observed for chemotherapy (median 2.8 months) and NHA (median 5.1 months), respectively. The most common LOT sequences were NHA â†’ NHA (29.4% of patients with ≥ 2 LOTs) and NHA â†’ NHA â†’ chemotherapy (16.7% of patients with ≥ 3 LOTs). In Kaplan-Meier analyses, the median OS was 19.4, 14.6, and 11.1 months post-1L, 2L, and 3L start, respectively. Patients who moved rapidly through LOTs had an increased risk of death. CONCLUSIONS: NHA were widely used as 1L therapy in mCRPC patients from 2013 to 2019, but time on 1L NHA treatment was on average < 6 months. While NHA â†’ NHA was the most observed 1L â†’ 2L LOT sequence, a plethora of other LOT sequences were observed. OS was poor, highlighting an unmet need for life-prolonging treatments.

Real-World Treatment Patterns, Clinical Outcomes, and Health Care Resource Utilization in Extensive-Stage Small Cell Lung Cancer in Canada.

The prognosis for extensive-stage small cell lung cancer (ES-SCLC) is poor. Real-world evidence can highlight the unmet clinical need within this population. We conducted a population-based cohort study of ES-SCLC patients diagnosed in a large Canadian province (2010-2018) using electronic medical records and administrative claims data. In all, 1941 ES-SCLC patients were included, of which 476 (25%) were recurrent cases. Median age at diagnosis was 70 years (range: 39-94) and 50.2% were men. Of the 1941 ES-SCLC patients, 29.5% received chemotherapy and radiotherapy, 17.0% chemotherapy alone, 8.7% radiotherapy alone, and 44.8% received best supportive care. Chemotherapy was initiated by 46.5%, 8.5%, and 1.4% of first-, second-, and third-line patients, with lower uptake for recurrent cases. Median survival from first-, second-, and third-line chemotherapy was 7.82 months (95% CI: 7.50-8.22), 5.72 months (95% CI: 4.90-6.87), and 3.83 months (95% CI: 2.99-4.60). Among patients who received first-line therapy, the 2-year and 5-year survival was 7.3% (95% CI: 5.7-9.2) and 2.9% (95% CI: 1.8-4.5). In conclusion, initiation of first-line treatment in ES-SCLC was low with significant attrition in subsequent lines. These results underscore the need for effective front-line treatments and highlight the potential for novel therapies to improve patient outcomes.

The number of prior lines of systemic therapy as a prognostic factor for patients with brain metastases treated with stereotactic radiosurgery: Results of a large single institution retrospective analysis.

OBJECTIVES: It is presently unknown whether patients with brain metastases from heavily pre-treated cancers have a significantly different prognosis than those with less pre-treatment. In this study we sought to identify whether the number of prior lines of systemic therapy are associated with clinical outcomes in patients with brain metastases who received stereotactic radiosurgery (SRS). PATIENTS AND METHODS: Between July 2000 and July 2017, 377 patients with brain metastases were treated with upfront SRS. We performed a large, single institution retrospective analysis of these patients. Kaplan Meier analysis was used to estimate survival times. Competing risk analysis was used to estimate times to local failure (LF) and distant brain failure (DBF). Multivariate analysis was performed to estimate the hazard ratios (HRs) for overall survival (OS), neurologic and non-neurologic death for patients with 1, 2 and 3+ lines of prior systemic therapy. RESULTS: Of the 1077 patients with brain metastases treated with SRS, 377 received prior systemic therapy with a median of 1 (range: 1-9) lines of prior therapy. Median OS was 8.70 months (95% CI, 7.9-9.5). Median OS for patients with 1 prior line of therapy, 2 prior lines of therapy and 3 or greater lines of therapy were 9.93-, 9.05-, and 6.18-months, respectively (log rank p = .04). Lines of therapy as a continuous variable was not associated with LF or DBF on competing risk analysis. The percentage of patients that died of neurological death was 36%. Greater prior lines of therapy (1 vs. 2 vs. 3 and greater) was associated with a greater likelihood of dying of non-neurologic death (gray's p = .01), but was not associated with likelihood of dying of neurologic death (p = .57). CONCLUSION: Lines of therapy are associated with OS and non-neurologic death but are not associated with neurologic death, LF or DBF.

Treatment of Patients With Metastatic Colorectal Cancer in a Real-World Scenario: Probability of Receiving Second and Further Lines of Therapy and Description of Clinical Benefit.

BACKGROUND: The optimal therapeutic strategy for metastatic colorectal cancer patients is still a matter of debate. There are no prognostic variables indicating how many lines individual patients ought to receive, and whether later lines could be effective even when earlier ones were not. PATIENTS AND METHODS: We retrospectively collected data from 420 consecutive patients with metastatic colorectal cancer at our institution, describing the proportion of patients who received second or later lines of therapy and the chance of a line of treatment being active when the previous line was not. For each line of treatment, we defined clinical benefit as the probability of not having had evidence of disease progression 6 months after the start of chemotherapy. RESULTS: Of the 373 patients with disease progression after first-line chemotherapy (1L), 277 received a second line (2L) (probability of being submitted to a 2L (P(2L)) = 74.3%): 143 (63.3%) of 226 received a 3L (P(3L)), and 56 (45.9%) of 122 were submitted to a 4L (P(4L)). Joint probabilities were: 2L 74.3%, 3L 47.0%, and 4L 21.6%. A total of 298 (71.5%) of 417 patients had a clinical benefit with 1L; 134 (48.6%) of 276 with 2L; 50 (35.2%) of 142 with 3L; and 12 (25.0%) of 48 with 4L. Taking all these data together, 31% of the patients who experienced early progression at 1L had the chance to have a clinical benefit with any further lines. CONCLUSION: Our study demonstrated that of 4 patients submitted to a 1L, about 3 will receive a 2L, about 2 a 3L, and nearly 1 a 4L. Later lines could be beneficial even though earlier ones were not.