BackgroundAnti-PD-(L)1 agents are standard of care treatments in various cancers but predictive factors for therapy selection are limited. We hypothesised that markers of systemic inflammation would predict adverse outcomes in multiple cancers treated with anti-PD-(L)1 agents.Material and methodsDiscovery cohort consisted of patients who were treated with anti-programmed cell death protein-1 (PD-1) agents for advanced melanoma (MEL), non-small cell lung cancer (NSCLC) or renal and bladder cancers (GU) at Oulu University Hospital and had pretreatment C reactive protein (CRP), or neutrophil/lymphocyte values available. As a validation cohort, we collected patients treated with anti-PD-1 agents from three other hospitals in Finland.ResultsIn the discovery cohort (n=56, MEL n=23, GU n=17, NSCLC n=16), elevated CRP over the upper limit of normal (ULN) (>10 mg/mL) indicated poor progression-free (PFS; p=0.005) and overall survival (OS; p=0.000004) in the whole population and in MEL subgroup. Elevated neutrophil-to-lymphocyte ratio (>2.65) also indicated inferior PFS (p=0.02) and OS (p=0.009). In the validation cohort (n=107, MEL n=44, NSCLC n=42, GU n=17, other n=4), CRP over ULN also was a strong indicator for poor PFS (p=0.0000008), and OS (p=0.000006) in the whole population, and in MEL and NSCLC also.ConclusionsSystemic inflammation suggested by elevated CRP is a very strong indicator for adverse prognosis on patients treated with anti-PD-(L)1 agents and has a potential negative predictive value for treatment with anti-PD-(L)1 agents. Prospective trials should investigate whether patients with elevated CRP gain any significant benefit from anti-PD-1 therapy.

Purpose Patient-reported outcome (PRO) follow-up has been shown to improve quality of life (QoL) and survival of cancer patients receiving chemotherapy. Kaiku Health application is a web-based electronic PRO (ePRO) tool which is designed for follow-up of cancer patients receiving immune checkpoint inhibitors (ICI). Purpose of the current study is to investigate whether symptoms collected by Kaiku Health ePRO tool on cancer patients receiving immune checkpoint inhibitors (ICI) follows to symptoms reported in clinical trials and whether coupling of specific symptoms does occur. Methods We retrospectively collected data on symptom timing and severity, and QoL of patients followed with Kaiku Health IO module in two Finnish cancer centers between 2017 and 2018. Kaiku Health IO module consists of 18 adaptive questions, which assess the presence and severity of symptoms. Patients were requested (via e-mail) to fill online symptom questionnaires with 3–7 day interval and QoL questionnaires (QLQ-C30) with 1–2 month interval. Results The IO module was used to follow 37 patients who had filled in total 559 symptom questionnaires. There was good adherence to ePRO follow-up with a median of 11 questionnaires filled per patient. The reported symptoms and their severity follow closely what has been seen in clinical trials investigating ICIs. Correlation analysis of the symptoms showed the strongest positive correlations between itching and rash; nausea and vomiting, decreased appetite, or stomach pain; cough and shortness of breath. Conclusions The results of the current study suggest that real-world symptom data collected through the ePRO application on cancer patients receiving ICI therapy aligns with the data from clinical trials. Correlations between different symptoms occur, which might reflect therapeutic efficiency, side effects, or tumor progression. These correlations should be further investigated with data coupled to clinical outcomes.

Background: Most clinical trials have investigated PD-(L)1 agents until disease progression or severe side effects, but the optimal duration of the treatment remains to be elucidated. Our institutional guideline has restricted maximal PD-(L)1 therapy length to 6 months, and therefore our cohort provides a unique opportunity to investigate the effects of short PD-1 therapy. Methods: We retrospectively collected all patients who had been treated with PD-1 therapy for metastatic cancer at Oulu University Hospital from 2014 to 2018. Clinical variables, treatment history, and survival were collected. Results: A total of 59 patients received PD-1 therapy for metastatic disease in lung and genitourinary (renal and bladder) cancers as well as melanoma. Median overall survival was close to what has been seen in clinical trials. Seventeen patients had PD-1 therapy discontinued in response, most of them because of reaching the maximal restricted PD-1 therapy length (n = 12, 70.6%). Patients whose therapy was discontinued in response experienced a long immuno-oncology (IO) therapy-free survival (median 12 months), and only 6 patients had need for therapy re-initiation during the follow-up. We also investigated alternative response evaluation criteria which outperformed conventional RECIST 1.1 in predicting IO therapy-free survival. Conclusion: The results of the current study suggest that patients whose PD-1 therapy has been discontinued in response can have a long IO therapy-free period without need for a next line of therapy.

Background Cancer immunotherapy (CIT), as a monotherapy or in combination with chemotherapy, has been shown to extend overall survival in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). However, patients experience treatment-related symptoms that they are required to recall between hospital visits. Digital patient monitoring and management (DPMM) tools may improve clinical practice by allowing real-time symptom reporting. Objective This proof-of-concept pilot study assessed patient and health care professional (HCP) adoption of our DPMM tool, which was designed specifically for patients with advanced or metastatic NSCLC treated with CIT, and the tool’s impact on clinical care. Methods Four advisory boards were assembled in order to co-develop a drug- and indication-specific CIT (CIT+) module, based on a generic CIT DPMM tool from Kaiku Health, Helsinki, Finland. A total of 45 patients treated with second-line single-agent CIT (ie, atezolizumab or otherwise) for advanced or metastatic NSCLC, as well as HCPs, whose exact number was decided by the clinics, were recruited from 10 clinics in Germany, Finland, and Switzerland between February and May 2019. All clinics were provided with the Kaiku Health generic CIT DPMM tool, including our CIT+ module. Data on user experience, overall satisfaction, and impact of the tool on clinical practice were collected using anonymized surveys—answers ranged from 1 (low agreement) to 5 (high agreement)—and HCP interviews; surveys and interviews consisted of closed-ended Likert scales and open-ended questions, respectively. The first survey was conducted after 2 months of DPMM use, and a second survey and HCP interviews were conducted at study end (ie, after ≥3 months of DPMM use); only a subgroup of HCPs from each clinic responded to the surveys and interviews. Survey data were analyzed quantitatively; interviews were recorded, transcribed verbatim, and translated into English, where applicable, for coding and qualitative thematic analysis. Results Among interim survey respondents (N=51: 13 [25%] nurses, 11 [22%] physicians, and 27 [53%] patients), mean rankings of the tool’s seven usability attributes ranged from 3.2 to 4.4 (nurses), 3.7 to 4.5 (physicians), and 3.7 to 4.2 (patients). At the end-of-study survey (N=48: 19 [40%] nurses, 8 [17%] physicians, and 21 [44%] patients), most respondents agreed that the tool facilitated more efficient and focused discussions between patients and HCPs (nurses and patients: mean rating 4.2, SD 0.8; physicians: mean rating 4.4, SD 0.8) and allowed HCPs to tailor discussions with patients (mean rating 4.35, SD 0.65). The standalone tool was well integrated into HCP daily clinical workflow (mean rating 3.80, SD 0.75), enabled workflow optimization between physicians and nurses (mean rating 3.75, SD 0.80), and saved time by decreasing phone consultations (mean rating 3.75, SD 1.00) and patient visits (mean rating 3.45, SD 1.20). Workload was the most common challenge of tool use among respondents (12/19, 63%). Conclusions Our results demonstrate high user satisfaction and acceptance of DPMM tools by HCPs and patients, and highlight the improvements to clinical care in patients with advanced or metastatic NSCLC treated with CIT monotherapy. However, further integration of the tool into the clinical information technology data flow is required. Future studies or registries using our DPMM tool may provide insights into significant effects on patient quality of life or health-economic benefits.

Background Immune checkpoint inhibitors (ICIs) have become a standard of care for various tumor types. Their unique spectrum of side effects demands continuous and long-lasting assessment of symptoms. Electronic patient-reported outcome (ePRO) follow-up has been shown to improve survival and quality of life of cancer patients treated with chemotherapy. Objective This study aimed to investigate whether ePRO follow-up of cancer patients treated with ICIs is feasible. The study analyzed (1) the variety of patient reported symptoms, (2) etiology of alerts, (3) symptom correlations, and (4) patient compliance. Methods In this prospective, one-arm, multi-institutional study, we recruited adult cancer patients whose advanced cancer was treated with anti-programmed cell death protein 1 (PD)- ligand (L)1 agents in outpatient settings. The ePRO tool consisted of a weekly questionnaire evaluating the presence of typical side effects, with an algorithm assessing the severity of the symptom according to National Cancer Institute Common Terminology Criteria for Adverse Events and an urgency algorithm sending alerts to the care team. A patient experience survey was conducted monthly. The patients were followed up to 6 months or until disease progression. Results A total of 889 symptom questionnaires was completed by 37 patients (lung cancer, n=15; melanoma, n=9; genitourinary cancer, n=9; head and neck cancer, n=4). Patients showed good adherence to ePRO follow-up. The most common grade 1 symptoms were fatigue (28%) and itching (13%), grade 2 symptoms were loss of appetite (12%) and nausea (12%), and grade 3-4 symptoms were cough (6%) and loss of appetite (4%). The most common reasons for alerts were loss of appetite and shortness of breath. In the treatment benefit analysis, positive correlations were seen between clinical benefit and itching as well as progressive disease and chest pain. Conclusions According to the results, ePRO follow-up of cancer patients receiving ICIs is feasible. ePROs capture a wide range of symptoms. Some symptoms correlate to treatment benefit, suggesting that individual prediction models could be generated. Trial Registration Clinical Trials Register, NCT3928938; https://clinicaltrials.gov/ct2/show/NCT03928938