Patient Reported Outcome Measurements (PROMs) Impact on Clinical Outcome in firsT Line settIng Non- Small-Cell Lung Cancer (NSCLC) According to Chemo- Immunotherapy reGimen (PROMOTING)

Patient Reported Outcome Measurements (PROMs) Impact on Clinical Outcome in firsT Line settIng Non- Small-Cell Lung Cancer (NSCLC) According to Chemo- Immunotherapy reGimen (PROMOTING)

A multicenter, national pharmacological observational study that has as its overall goal to implement a set of validated and agreed upon European-wide questionnaires (PROMs - patient's reported outcomes) to assess patients' perceptions of aspects of their lives based on the treatment they are receiving.

Specifically, with the research we present here, we aim to obtain data on patients' health and condition, including quality of life, symptom status, physical function, mental health (anxiety and depression), sleep quality, and sexuality as useful indicators not only of patient well-being but also of the effectiveness of the treatment itself.

The study involves the following: patients will be asked to complete online questionnaires at the following timepoints: before the start of treatment, after 4 and 8 treatment cycles, and at disease progression.

Data will also be collected regarding the patient's oncological medical history, treatment performed, response to treatment at CT/PET reevaluations, any toxicities that arose during treatment.

Study Overview

• Status: Recruiting
• Conditions: PROMs
• Intervention / Treatment: Drug: Carboplatin/Cisplatin+Pemetrexed+Pembrolizumab/Cemiplimab for 4 cycles and then maintenance with Pemetrexed+Pembrolizumab/Cemiplimab up to 2 years or disease progression or unacceptable toxicity; Drug: Carboplatin/Cisplatin+Pemetrexed+Nivolumab+Ipilimumab for 2 cycles and then maintenance with Nivolumab q21 and Ipilimumab q42 up to 2 years or disease progression or unacceptable toxicity

Detailed Description

Patient-reported outcomes measures (PROMs) are tools to assess patients' views on aspects of their health and condition, including health-related quality of life, symptom status, physical function and mental health. In medical oncology, PROMs are emerging as useful indicators not only of patient well-being, but also of treatment efficacy. Measurement of quality of life (QoL) has an intrinsic role in the definition of treatment value and, in the absence of head-to-head comparisons showing differences in overall survival or other traditional endpoints, comparison in terms of QoL can usefully inform the choice among alternative treatment options. The recent availability of alternative strategies in advanced NSCLC, in particular different combination therapies in first line setting, requires models to support clinical decision in tailoring individual treatments. In this model, the integration of PROMs could be essential in promoting a patient-centered approach to cancer care.

EORTC QLQ-C-30, exploring general functioning, and EORTC LC-13, specific for lung cancer are the most used PROMs tools in thoracic oncology.

QoL is a complex and composite outcome, which includes different aspects of patients' well-being, such as anxiety, depression and emotional stress. The latter has been measured in patients with lung cancer using PHQ-9 and Generalized Anxiety Disorder 7-item scales. Of note, a significant association with reduced response and worse survival upon immunotherapy was reported, suggesting an impact of emotional stress on patients' immune system and consequently on treatment outcomes.

Considering the broad effect of immunotherapy on the endocrine system and hormones' functions, it is likely that sexual health and sleep, other nuances of the QoL field, could be also affected by immunotherapy. So far, both sexual and sleep dysfunctions have been poorly explored in clinical trials. Furthermore, "time toxicity" defined as number of days with physical contact with healthcare system, could significantly affect patients' emotional distress sphere and has never been explored in NSCLC upon chemo-immunotherapy combinations.

Based on these assumptions, we believe that chemo-ICI (4 cycles of platinum-based doublet chemotherapy + anti- PD-1 followed by single agent chemo and immunotherapy maintenance) or double-ICI chemo (2 cycles of platinum-based doublet chemotherapy + anti-PD-1 and anti-CTLA-4, followed by maintenance with combo immunotherapy) regimens may have distinct effects on several QoL domains. This could be due to the intrinsic differences in the drugs used (i.e. addition of anti-CTLA-4 agents), treatment related toxicities and different tumor shrinkage activity.

The present study aims to compare QoL by validated questionnaires (EORTC QLQ-C-30, EORTC LC13) in the two above mentioned cohorts of patients with metastatic lung adenocarcinoma, having an additional focus in sexual (EORTC QLQ-SH-22), emotional stress (PHQ-9, Generalized Anxiety Disorder 7-item scale) and sleep disorders (PSQI) as previously reported. Time toxicity will be measured by analyzing the time patients spend in contact with healthcare system, such as visits and treatment. A defined cut off considers time toxicity severe when it exceeds 20% of the total care time.

• Study Type: Observational
• Enrollment (Estimated): 144

Contacts and Locations

• Study Contact: Name: Sara Oresti, Medical Oncologist; Phone Number: +39 022643 8195; Email: oresti.sara@hsr.it

Study Locations

• Italy
  • Italy
    • Milan, Italy, Italy, 20132
      • Recruiting
      • IRCCS Ospedale San Raffaele
      • Contact: Sara Oresti, Medical Oncologist; Phone Number: + 39 026438195; Email: oresti.sara@hsr.it
      • Principal Investigator: Sara Oresti

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with diagnosis of unresectable or advanced NSCLC eligible for first line chemo- ICI (Cohort A) or double ICI-chemo (Cohort B) regimens.

Up to 50 patients with squamous histology, treated with any chemo- immunotherapy scheme will be monitored for QoL parameters as a prospective exploratory observational cohort and will not be included in the sample size calculation.

Description

Inclusion Criteria:

• Age > 18 years
• Diagnosis of Stage IV NSCLC with PD-L1 <50%, without actionable genomic alterations
• Signed Informed Consent Form (ICF) to the study
• Patients eligible to receive first line treatment with combo chemo-immuno treatments as standard of care

Exclusion Criteria:

- Patients unable to fill the questionnaires due to neurological comorbidities

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A: patient treated with chemo-ICI regimen as first line therapy; Cohort A: Carboplatin/Cisplatin+Pemetrexed+Pembrolizumab/Cemiplimab (Keynote 189, EmpowerLung 3) for 4 cycles and then maintenance with Pemetrexed+Pembrolizumab/Cemiplimab up to 2 years or disease progression or unacceptable toxicity	Drug: Carboplatin/Cisplatin+Pemetrexed+Pembrolizumab/Cemiplimab for 4 cycles and then maintenance with Pemetrexed+Pembrolizumab/Cemiplimab up to 2 years or disease progression or unacceptable toxicity; Cohort A: Carboplatin/Cisplatin+Pemetrexed+Pembrolizumab/Cemiplimab (Keynote 189, EmpowerLung 3) for 4 cycles and then maintenance with Pemetrexed+Pembrolizumab/Cemiplimab up to 2 years or disease progression or unacceptable toxicity
Cohort B: patient treated with double ICI-chemo regimen as first line therapy; Cohort B: Carboplatin/Cisplatin+Pemetrexed+Nivolumab+Ipilimumab (CheckMate9LA) for 2 cycles and then maintenance with Nivolumab q21 and Ipilimumab q42 up to 2 years or disease progression or unacceptable toxicity	Drug: Carboplatin/Cisplatin+Pemetrexed+Nivolumab+Ipilimumab for 2 cycles and then maintenance with Nivolumab q21 and Ipilimumab q42 up to 2 years or disease progression or unacceptable toxicity; Cohort B: Carboplatin/Cisplatin+Pemetrexed+Nivolumab+Ipilimumab (CheckMate9LA) for 2 cycles and then maintenance with Nivolumab q21 and Ipilimumab q42 up to 2 years or disease progression or unacceptable toxicity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate what kind of first line treatment for metastatic lung adenocarcinoma has a better impact on quality of life of the patients	QoL domains assessed by EORTC QLQ-C-30 and LC13 at baseline and after 4 cycles. All questionnaires used in this study are validated questionnaires	Baseline, after 4 cycles

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the impact on overall survival of all the PROMs items under investigation	QoL domains assessed by EORTC QLQ-C-30 and LC13 after 8 cycles of treatment and at disease progression; Sleep (PSQI), emotional stress (PHQ-9, GAD 7-item scale), sexual health ((EORTC QLQ-SH- 22) and time toxicity after 4 cycles, 8 cycles, and at disease progression; Overall Survival	After 4 cycles, after 8 cycles, and at disease progression

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
- To assess the impact on overall survival of all the PROMs items under investigation in squamous NSCLC	QoL domains assessed by EORTC QLQ-C-30 and LC13 between double ICI-chemo or chemo- ICI regimens in patients with metastatic squamous NSCLC after 4 cycles, 8 cycles, and at disease progression.	After 4 cycles, after 8 cycles and at disease progression
- To assess the impact on PFS and RR in patients receiving different first line regimens	Progression-Free Survival (PFS) and Response Rate (RR) in each Cohort	Baseline, after 4 cycles, after 8 cycles and at disease progression

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele
• Collaborators: ASST Grande Ospedale Metropolitano Niguarda; AOU Città della Salute e della Scienza di Torino - Presidio Molinette; Fondazione Policlinico Campus Bio-Medico; ASST Lariana, Como; IRCCS Istituto Nazionale dei Tumori; IRCCS San Gerardo dei Tintori, Monza; ASST Spedali Civili di Brescia; Policlinico San Matteo Pavia; IRCCS Istituto Clinico Humanitas; Ospedale Vincenzo Monaldi

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: June 20, 2025
• First Submitted That Met QC Criteria: July 2, 2025
• First Posted (Actual): July 11, 2025

Study Record Updates

• Last Update Posted (Estimated): September 3, 2025
• Last Update Submitted That Met QC Criteria: August 31, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: immunotherapy; NSCLC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Organic Chemicals; Coordination Complexes; Carboplatin; cemiplimab
• Other Study ID Numbers: PROMOTING

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No