ESMO Real World Data and Digital Oncology最新文献

Background

Neoadjuvant chemotherapy (NAC) with the addition of pembrolizumab has become the standard of care for early-stage II-III triple-negative breast cancer (TNBC). The real-world safety of this regimen is critical to assess in this subset of patients treated with curative intent, since many of the immune-related events observed can be long-lasting or irreversible.

Patients and methods

We retrospectively analyzed the medical records for the initial 100 patients with early-stage TNBC treated with NAC and pembrolizumab at a single comprehensive cancer center between April 2022 and April 2023. We used descriptive analyses to assess treatment exposure, real-world safety and effectiveness of this combination. Treatment-related toxicities were reported according to the Common Terminology Criteria for Adverse Events v5.0. Follow-up extended until the end of the adjuvant phase.

Results

The median age of the patients was 52 years, and 21% were identified as germline pathogenic BRCA1/2 alteration carriers. Treatment discontinuation rate due to adverse events (AEs) in the neoadjuvant phase was 35%. Half of the patients (50%) required dose reductions of at least one chemotherapy drug. The total rate of pathological complete response/residual cancer burden 0 was 58%. A total of 61% experienced at least one immune-related AE (irAE), 30% of which were grade 3-5. We documented one grade 5 toxicity following immune-related myocarditis.

Conclusion

In this real-life cohort, treatment discontinuation was frequent and linked to treatment toxicity of either chemotherapy or pembrolizumab. We report a higher rate of all grade and grade ≥3 irAEs as compared to the rates documented in the pivotal KEYNOTE 522 trial. The effectiveness of neoadjuvant chemo-immunotherapy for the treatment of stage II-III TNBC was similar to that reported in the literature.

Background

Osimertinib has been the standard of care in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We evaluated outcomes between osimertinib and first/second-generation (1G/2G) EGFR-tyrosine kinase inhibitors (TKIs) as first-line (1L), and investigated how T790M status and sequential osimertinib after 1G/2G EGFR-TKI failure affected overall survival (OS).

Materials and methods

We retrospectively evaluated the outcomes of patients with advanced NSCLC harboring exon 19 deletion or L858R mutation who received osimertinib and 1G/2G EGFR-TKIs as 1L treatment from January 2015 to March 2021. In the exploratory analysis, we analyzed the outcomes among three groups: osimertinib as 1L (1L-Osi), 1L 1G/2G EGFR-TKIs followed by osimertinib (2L-Osi), and 1L 1G/2G EGFR-TKIs without osimertinib (No-Osi). Propensity score matching (PSM) and 12-month landmark analysis were used to mitigate selection bias and immortal time bias.

Results

Of 485 patients, 213 and 272 received 1L osimertinib and 1L 1G/2G EGFR-TKIs. All 2L-Osi patients had T790M mutations after 1G/2G EGFR-TKI failure. OS did not differ according to 1L EGFR-TKIs [osimertinib versus 1G/2G EGFR-TKIs; 33.7 versus 41.8 months; hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.65-1.29]. In the 12-month landmark analysis, the median OS was 34.4 months [95% CI 21.3 months-not reached (NR)] in 1L-Osi, 63.8 months (95% CI 46.0 months-NR) in 2L-Osi, and 22.5 months (95% CI 19.0-35.3 months) in No-Osi. After PSM, similar results were observed.

Conclusions

There was no significant difference in OS between osimertinib and 1G/2G EGFR-TKIs as 1L treatment in patients with EGFR-mutant NSCLC. However, 2L osimertinib following 1L 1G/2G EGFR-TKIs in patients who would acquire T790M mutation has been linked to a better prognosis compared to 1L osimertinib.

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.