ESMO Real World Data and Digital Oncology最新文献

Background

New breakthroughs in precision therapies are transforming cancer care for patients with advanced non-small-cell lung cancer (NSCLC). To this effect, comprehensive genomic profiling (CGP) has emerged as a streamlined workflow to test for all relevant tumor biomarkers within a single assay. Despite this, there are still significant gaps in access to CGP testing, with many patients only tested for a subset of biomarkers or not tested at all.

Materials and methods

We assessed the clinical impact of wide deployment of an in-house CGP assay at a large health care system in the United States by analyzing a cohort of advanced-stage NSCLC patients who received CGP testing and a retrospective cohort that was tested with a prior-generation 50-gene assay (small panel).

Results

Seventy-seven percent of CGP-tested NSCLC patients had one or more tumor biomarkers that were actionable for a precision therapy compared to 63% of small panel-tested patients. CGP-tested patients with an actionable biomarker received appropriate precision therapies at a higher rate than small panel-tested patients (64% versus 50%, P < 0.001), and there were marked improvements in survival outcomes for patients tested with CGP [median overall survival (OS) 15.7 months versus 7 months, P < 0.0001].

Conclusions

These data demonstrate clear precision therapy selection and patient OS benefits from universal access to CGP testing. Despite this, not all patients with an actionable biomarker received a precision therapy, suggesting that there are still gaps between access to CGP testing and access to precision therapies.

Background

Biliary tract cancers (BTCs), a heterogeneous group of cancers arising from the biliary tract, account for ∼15% of primary liver cancers. Patients are often diagnosed with advanced disease, resulting in poor prognoses and documented 5-year survival rates of <2%. The aim of this study was to describe real-world treatment patterns and outcomes among patients with advanced BTC in France, Germany, Italy, Spain, and the UK.

Patients and methods

A retrospective, physician-abstracted chart review survey was conducted between May 2018 and October 2021. Data were abstracted from medical charts of adult patients diagnosed with advanced BTC who initiated treatment with first-line (1L) systemic therapy. Patient characteristics, treatment patterns, and clinical outcomes were summarized descriptively.

Results

In total, 196 physicians provided data for 792 advanced BTC patients who initiated 1L systemic therapy. Mean age was 65.7 years and most of the patients were male (62.6%). At data abstraction 56.1% were deceased. The most frequently prescribed 1L systemic treatment was cisplatin–gemcitabine (47.9%). The median 1L treatment duration was 5.3 months. Additionally, 33.5% of patients received 2L and 4.5% received 3L+ treatment. Median real-world overall survival from index date was 13.4 months, with substantial regional variation.

Conclusions

This study supports extant data detailing that presentation at an advanced stage may contribute to the poor outcomes of BTC patients. There are significant implications for awareness and guideline-driven pathway changes to improve outcomes for these poorly served patients.

Recent advancements in health care digitalization opened the collection and availability of big data, whose analysis requires artificial intelligence-based technologies to facilitate the development of predictive tools supporting decision making in clinical practice. In this context, the idea of constructing ‘digital worlds’ to evaluate the performance of such novel tools becomes more attractive. Digital twins (DTs) are ‘digital objects’ characterized by a bi-directional interaction with their ‘real-world counterparts’. DTs aim to enhance predictions further by leveraging both the predictive capabilities of digital simulations and the continuous updating of real-life data—ideally incorporating clinical records, multiomics data, and patient-reported outcomes. DTs can potentially integrate these diverse data into virtual models applicable across pre-clinical to clinical studies. Running simulations in silico on cancer cells or cancer patients’ DTs can provide valuable insights into cancer biology, clinical practice, and health care education, with the added value of reducing costs and overcoming many common limitations of current studies (limited number of variables, challenges in recruiting patients with rare tumors, lack of real-life feedback). Despite their significant potential, DTs are still in their infancy, facing numerous unsolved technical and ethical challenges that hinder their application in clinical practice.

Background

Dual blockade therapy encorafenib–cetuximab (EC) was recently established as the standard of care for second- or third-line treatment for BRAF^V600E-mutated metastatic colorectal cancer (mCRC) patients based on BEACON phase III study results. The CONFIDENCE study aims to provide insight about the real-world (RW) safety and effectiveness of EC in a Spanish cohort.

Materials and methods

This retrospective study included BRAF^V600E-mutated mCRC patients treated in second line with EC in the RW setting. The primary endpoint (EC effectiveness) was measured by progression-free survival (PFS) and overall survival (OS). Key secondary endpoints were overall response rate (ORR), disease control rate (DCR), duration of response (DoR), potential factors affecting PFS and OS and safety.

Results

Eighty-one patients were included after at least 5 months of follow-up before study onset, 50.6% female with a median age of 66.1 years. Overall, 65% of patients debuted with synchronous metastatic disease. Patients received a median of six EC cycles. The median OS and PFS after 9.7 months of follow-up were 12.6 and 5.0 months, respectively. The median DoR was 5.8 months. ORR was 33.8% and DCR was 68.8%. Alkaline phosphatase, neutrophil/lymphocyte ratio and three or more metastatic lesions were accurate prognostic factors for OS. Additionally, the presence of liver metastases has prognostic value for PFS. The most reported adverse events (AEs) were skin-related toxicities (43.2%). Grade ≥3 AEs occurred in 13.5% of patients.

Conclusions

Our results align with the BEACON trial results, confirming the safety and efficacy of EC in the RW setting and additionally provide insight about survival prognostic factors.

Investing in cancer prevention can be cost-effective. However, this requires significant changes both inside and outside the health care system. The core of the preventive strategy is the assignment of an individual risk level of developing cancer. Artificial intelligence (AI), which has emerged as a tool to reduce errors and confusion in data collection and analysis, has helped accelerate recent advances in identifying circulating markers to generate predictive methods. With predictive models applied to increasingly less invasive and repeatable analytic tests, the risk is no longer assigned but profiled directly on the individual over time. On this basis, the probability of early cancer diagnosis is increased and at the same time, proactive preventive medicine transits from offering lifestyle recommendations to guiding specific treatments to reduce the risk. Despite these promises, AI-based predictive models also present challenges in clinical implementation. Addressing these challenges is crucial to minimizing the future burdens associated with fighting cancer.

Background

The role of real-world evidence (RWE) for clinical efficacy regulatory evaluation remains unclear. We aimed to assess and describe the reported use of RWE for clinical efficacy evaluation of authorised targeted therapies for treatment of solid malignancies in Europe.

Design

We studied all authorised indications of targeted therapies for the treatment of solid malignancies granted by the European Medicines Agency between 2018 and 2022. Data were retrieved in March 2023 from European Public Assessment Reports (EPARs). We evaluated the frequency of RWE use for clinical efficacy evaluation and its role based on the reported information in the EPAR, and assessed characteristics and risk of bias of published studies.

Results

Out of 75 authorised indications identified, most related to the treatment of patients with lung (21.3%) or breast (20.0%) cacer, and to advanced settings (89.3%). The use of RWE for clinical efficacy evaluation was reported in the EPAR of 16 (21.3%) indications, tending to increase overtime (15.0%-35.7% in 2018-2022). RWE was more frequently considered in lung (37.5%) and breast (33.3%) cancer indications, for antibody–drug conjugates (60.0%), and conditional approvals (46.7%). We classified RWE’s role as ‘supportive’ confirmatory evidence in 12 of 16 (75.0%) indications. RWE studies were mostly analytical (57.1%), non-international (92.9%), retrospective cohort studies (57.1%), and originated from the United States (78.6%). High or serious risk of bias was identified in different domains of most studies assessed.

Conclusions

RWE was reported to be used for clinical efficacy regulatory evaluation in 21% of targeted therapy indications for solid malignancies, with an increasing trend over time.

Many years have passed since the pathology report was all about a single-sentence diagnosis based on morphology. The pathology report is an invaluable source of data that needs to evolve from a narrative reporting to a synoptic reporting system by standardizing data elements to ensure consistency and structured formats that improve completeness, interoperability, and scalability across different health care systems. The convergence of technology, structured data, and artificial intelligence propels the field of pathology toward a future where the synthesis of information benefits not only health care professionals and patients but also serves as a wellspring of knowledge for machines, paving the way for unprecedented strides in data mining and health care innovation.

Background

Trastuzumab emtansine (T-DM1), the first antibody–drug conjugate targeting human epidermal growth factor receptor 2 (HER2), has provided new alternatives for metastatic breast cancer (mBC) treatment, and for early-stage breast cancer (esBC) since 2020. We characterized T-DM1 users and assessed the risk of hospitalisation for certain adverse events.

Materials and methods

Using data from the French National Health Data System (SNDS), we identified patients receiving T-DM1 from 2014 to 2022. Sociodemographic data, medical history, and overall survival were described by indication. The risk of adverse event-related hospitalisation was quantified.

Results

We included 12 822 patients initiating T-DM1 treatment in the study: 9232 (72%) with mBC (median age: 59 years, 54.6% with at least one comorbid condition) and 3590 (28%) with esBC (median age: 54 years, 33.9% with at least one comorbid condition). In mBC, median overall survival was 32.6 months, showing a gradual improvement over the years. At 1 year, 75.8% of patients had discontinued treatment and 22.0% had died. Patients in the study faced higher hospitalisation risks than those with incident breast cancer, with increases of 5.7 and 10.5 times for thrombocytopenia, 3.0 and 4.5 times for interstitial lung disease, 3.3 and 5.9 times for acute liver injury, and 2.3 and 7.3 times for sepsis, for esBC and mBC, respectively.

Conclusions

Real-world T-DM1 users frequently present with comorbid conditions and prior treatments, with a higher risk of hospitalisation for severe toxicity events than the general population of incident breast cancers. This study highlights the importance of monitoring treated patients to manage the risk of toxicity and prevent treatment discontinuation.

Background

Real-world data (RWD) can contextualize clinical trial data. We present real-world evidence that supplemented the single-arm DESTINY-Breast01 trial, which assessed the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1).

Patients and methods

Patients from the French Epidemiology Strategy and Medical Economics (ESME) mBC database who initiated treatment for HER2+ mBC between 1 January 2008 and 31 December 2016, and received one or more treatment lines following T-DM1 were propensity score matched 1 : 1 to patients from DESTINY-Breast01 to create an ESME DB-01 matched cohort. Treatment patterns, real-world best overall response, real-world objective response rate (rwORR), real-world disease control rate (rwDCR), real-world progression-free survival (rwPFS), and overall survival (OS) were estimated, including by prior pertuzumab exposure and de novo/relapsed mBC status.

Results

A total of 137 patients from the ESME mBC database (78 received prior pertuzumab, 59 did not) were matched to 137 patients from DESTINY-Breast01. In the ESME DB-01 matched cohort, 73.7% received an anti-HER2 drug after T-DM1 treatment. The rwORR was 12.2% (95% confidence interval [CI] 6.2% to 18.2%; only partial responses) and rwDCR was 73.9% (95% CI 65.9% to 81.9%). The median rwPFS was 4.7 months (95% CI 3.8-6.0 months) and similar regardless of prior pertuzumab exposure or de novo/relapsed mBC status. The median OS was 24.1 months (95% CI 18.5-26.4 months) and longer in patients naive to versus exposed to pertuzumab and in patients with de novo versus relapsed mBC.

Conclusion

These RWD contextualized results of DESTINY-Breast01 and demonstrated an unmet medical need in patients with HER2+ mBC after T-DM1 treatment.