ESMO Real World Data and Digital Oncology最新文献

Background

The introductions of immunotherapy and first-line combinations have led to major changes in systemic anti-cancer treatment (SACT) options and outcomes in metastatic renal cell carcinoma (mRCC).

Objectives

To evaluate current real-world UK practice in the immunotherapy era looking at survival outcomes by International Metastatic RCC Database Consortium (IMDC) risk stratification and prescribing patterns/drop-off rates of SACT in mRCC.

Materials and methods

This is a retrospective multi-institutional cohort of SACT patients for mRCC at 17 centres across the UK from 1 January 2018 and 30 June 2021. Patient characteristics, IMDC risk group and lines of therapy were recorded. Overall survival (OS) and progression-free survival (PFS) for IMDC groups were analysed.

Results

Of the 1319 patients, 22.3%, 52.7% and 24.3% were IMDC group favourable, intermediate and poor, respectively. Across all risk groups and censoring for patients who have not progressed on their current therapy line, 59.2%, 23.5% and 6.3 % of first-line patients with SACT received second-, third- and fourth-line treatments; 40.1%, 33.2% and 44.2%, respectively, did not receive immunotherapy at any stage in their treatment. Median PFS was statistically different by IMDC risk group: 14.0, 8.2 and 4.8 months in the favourable, intermediate and poor groups (P < 0.0001). Median OS was statistically different by risk group and were 40.9, 24.1 and 10.2 months for favourable, intermediate and poor risk groups, respectively.

Conclusions

The majority of patients receive only one or two treatment lines in mRCC. The IMDC prognostic risk groups remain valid in the immunotherapy era. A significant group of patients in this cohort did not receive immunotherapy at any stage.

Background

The current therapy for advanced non-small-cell lung cancer (NSCLC) often incorporates frontline use of programmed death (ligand) 1 [PD-(L)1] inhibitors concomitantly or sequentially with platinum-based chemotherapy. For patients whose cancer then progresses, the impact of prior immunotherapy on the efficacy of subsequent chemotherapy remains unclear. This retrospective study aimed to evaluate survival with taxane-containing regimens after prior chemotherapy and immunotherapy.

Methods

Using a US nationwide, longitudinal deidentified database, we selected patients ≥18 years old with unresectable stage IIIB-IV NSCLC, without actionable mutations, who had ECOG performance status of 0-1 when initiating a taxane-containing regimen from 4 March 2015 to 31 May 2021 after prior PD-(L)1 inhibitor and platinum-based chemotherapy, concomitantly or sequentially. Overall survival (OS) was estimated using the Kaplan-Meier method. The data cut-off was 31 May 2022.

Results

Of 587 eligible patients [median age, 68 years, 316 (54%) male, 560 (95%) with nonsquamous NSCLC], 528 (90%) had received one to two prior lines of therapy before taxane monotherapy (195 patients; 33%) or combination therapy (392; 67%). The median patient follow-up to death or data cut-off was 9.2 months (range <0.1-71.8 months). The median OS from taxane initiation was 9.0 months [95% confidence interval (CI) 8.1-9.6 months] and OS rates were 39% and 16% at 12 and 24 months, respectively. The median OS was similar with taxane monotherapy (9.0 months; 95% CI 8.1-11.2 months) and taxane combination therapy (8.8 months; 95% CI 7.5-9.6 months).

Conclusions

Survival with taxane-containing regimens after prior chemotherapy and immunotherapy is consistent with historical outcomes that predate immunotherapy. These findings highlight the need for more effective subsequent treatments after prior PD-(L)1 inhibitor and platinum-based chemotherapy for patients with advanced NSCLC without actionable mutations.

Background

Advanced urothelial cancer (aUC) is often characterized by rapid symptomatic disease progression, making early disease control of particular importance. Circulating tumor DNA (ctDNA) is a promising prognostic biomarker and emerging evidence shows that a single time point/measurement of ctDNA tumor fraction (TF) is prognostic in several other tumor types but has not yet been investigated in aUC. This study aimed to evaluate the prognostic value of ctDNA TF in aUC.

Patients and methods

This study used a cohort of patients from a de-identified nationwide (US-based) urothelial clinico-genomic database who underwent ctDNA testing using FoundationOne®Liquid or FoundationOne®Liquid CDx as part of routine care. Patient/disease characteristics and laboratory and treatment data were captured from the electronic health record. Real-world progression-free survival (rwPFS) and overall survival (rwOS) were evaluated by ctDNA TF while controlling for relevant covariates.

Results

Eighty-three patients with aUC were included. High ctDNA TF (≥1%) was associated with poor prognostic clinical features. High ctDNA TF also correlated with significantly reduced rwPFS in univariable analysis [hazard ratio (HR) 2.01, 95% CI (1.14-3.56), P = 0.01] and after correction for covariates [HR 2.37, 95% CI (0.99-5.66), P = 0.05]. There was a trend toward shorter rwOS in univariable [HR 1.71, 95% CI (0.87-3.36)] and multivariable [HR 1.55, (0.57-4.23)] analysis.

Conclusions

ctDNA TF is a prognostic biomarker in aUC with potential to inform expected longevity of patients. Uniform cohorts, with regard to treatments given and line of therapy, would help further evaluate the ability of ctDNA TF to identify patients with aggressive disease and inform the design of future studies to personalize therapeutic decision making.

Background

In 2022, the European Society for Medical Oncology (ESMO) guideline recommended the adoption of electronic patient-reported outcomes measures (ePROMs) in routine clinical practice for patients with cancer. The aim of this survey is to identify the critical issues that would arise in the implementation of ePROMs in daily oncology clinical practice from patients’ view.

Materials and methods

From March to April 2023, outpatients with cancer treated at Mauriziano Hospital in Turin (Italy) filled in a paper questionnaire. Seven questions dealt with the respondents’ characteristics, eight questions with the satisfaction about the current method used to collect information about patients’ symptoms and toxicities, and the opinion about several potentially critical issues for the implementation of ePROMs.

Results

Two hundred and twenty patients completed the survey. In current clinical practice, symptoms are mostly collected through verbal questions and paper-based questionnaires. Seventy-two percent of patients were satisfied with these methods; 82% were in favor of using ePROMs. Most patients were not concerned about privacy (82%), while a minority was concerned about possible lack of interest by clinicians in the symptoms digitally reported (14%) and the possible negative impact on doctor–patient relationship (39%). Seventy-seven percent of respondents declared to be familiar with technological tools and 83% were confident with the availability of internet connection.

Conclusions

In our center, most patients are satisfied with current methods of symptom monitoring and would also be in favor of the introduction of ePROMs. However, several aspects still need to be addressed for universal implementation of ePROMs in routine practice.

Background

This study explores the potential benefits of neoadjuvant chemotherapy in borderline resectable (BR) pancreatic adenocarcinoma. Despite neoadjuvant treatment (NAT) increasingly being utilised, uncertainty remains as to the optimal approach.

Patients and methods

This study assessed clinical outcomes for 218 consecutive BR patients from the PURPLE registry. We compared initial surgery (IS) to NAT overall, and between different chemotherapy regimens.

Results

Of 1314 non-metastatic patients enrolled, 218 (17%) were considered BR. Of 28 planned for IS, 11/28 (39%) had their tumour excised compared to 68/152 (45%) with NAT (P = 0.59). Among those who received NAT and were resected, 52/100 (52%) received FOLFIRINOX (P = 0.234) and 8/28 (29%) received nab-paclitaxel with gemcitabine (nabPGem). There was no difference in median overall survival (OS) [hazard ratio (HR) 0.72, P = 0.199] between pooled NAT versus IS. Neoadjuvant FOLFIRINOX was associated with improved R0 resection rates (26% versus 7%, P = 0.07) and lower perineural invasion (51% versus 82%, P = 0.02) compared to IS in resected specimens. Neoadjuvant FOLFIRINOX improved OS (HR 0.53, P = 0.02), with a 23% improvement in 2-year OS. There was no difference in survival outcomes between IS and nabPGem.

Conclusions

The results of our study suggest that neoadjuvant FOLFIRINOX could improve R0 resection rate and OS compared to IS.

Background

The treatment landscape of gastroesophageal cancer (GEC) is evolving. A better understanding of GEC biology and novel effective drugs would enhance the standard of care. To further improve outcomes for patients with GEC, it is crucial to evaluate treatment, response, survival, and patient-reported quality of life (QoL) in a real-world setting.

Materials and methods

SAPHIR is a prospective and retrospective, observational, multicenter, national cohort study on esophageal, gastric, or gastroesophageal junction cancers. The study is aimed at enrolling 900 patients with stage IV GEC receiving first-line systemic therapy (prospective data collection). Patients are enrolled at ∼150 sites from different health care sectors in Germany. Recruitment started in quarter 4 (Q4)/2019. Each patient will be observed for a maximum of 2 years. In a satellite project, recruitment of another 200 patients with stage IB-III GEC receiving pre-/perioperative chemotherapy or radiochemotherapy was conducted in Q1-2/2022 (retrospective, one-time data collection). SAPHIR will provide real-world data (RWD) on treatment preferences, molecular testing, and clinical outcomes including overall and health-related QoL. Furthermore, patients can give consent for donation of tumor tissue obtained during the course of routine clinical care for centralized biomarker research. Descriptive statistics and explorative analyses will be carried out.

Conclusions

SAPHIR aims to improve health care for patients with GEC by collecting RWD representative for all sectors in health care. This will provide information on routine clinical practice, efficacy, and evolving biomarker in GEC. Furthermore, evaluation of molecular data may allow for identification of response or resistance mechanisms to targeted and immunotherapy in GEC.

While the number of newly approved anticancer therapies has increased substantially in the past decade, there remains a need to bring effective treatments to patients more efficiently. In the United States and Europe, real-world data (RWD) are being utilized widely, including in regulatory submissions to assess the potential benefits of therapies in development and address the unmet needs of the patients with limited treatment options. In Japan, given the volume of annual new cancer cases and region-specific circumstances, oncology RWD are crucial for improving patient access to effective therapies. The development of such RWD is underway; a notable recent example is the use of the SCRUM-Japan Registry as a source of external control data in the regulatory approval of pertuzumab and trastuzumab for patients with HER2-positive metastatic colorectal cancer. In addition, electronic health records-based longitudinal, patient-level RWD in Japan are being curated by Flatiron Health K.K. (FHKK), the Japanese subsidiary of Flatiron Health, Inc., by leveraging both structured and unstructured data-processing methodologies developed in the United States over the past decade and tailoring the approach to local requirements. FHKK, in partnership with one of the flagship cancer hospitals in Japan, the National Cancer Center Hospital East (NCCHE), is constructing patient-level RWD in gastrointestinal and other cancers; the first datasets in gastrointestinal cancers will be provided in late 2023. As the curation of oncology RWD in Japan progresses, continuous expansion of the depth and breadth of the data is planned to improve and extend lives of people with cancer.