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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Mobocertinib (TAK-788) in EGFR Exon 20 Insertion+ Metastatic NSCLC: Patient-Reported Outcomes from EXCLAIM Extension
Maria Rosario Garcia Campelo1, Caicun Zhou2, Suresh S Ramalingam3
1Department of Medical Oncology, University Hospital Complex A Coruña, 15006 A Coruña, Spain.
Abstract:
Mobocertinib, an oral, first-in-class epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for EGFR exon 20 insertions (ex20ins), achieved durable responses in adults with previously treated EGFR ex20ins+ metastatic non-small cell lung cancer (mNSCLC) in the EXCLAIM extension cohort of a phase 1/2 study (N = 96; NCT02716116). We assessed patient-reported outcomes (PROs) with mobocertinib 160 mg once daily (28-day cycles) in EXCLAIM (N = 90) with the European Organisation for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (EORTC QLQ-C30) v3.0, lung cancer module (QLQ-LC13), EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire, and selected PRO Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire. Median treatment duration was 6.8 (range, 0.0-18.8) months (median follow-up: 13.0 [0.7-18.8] months; data cutoff: 1 November 2020). Clinically meaningful improvements in lung cancer symptoms measured by EORTC QLQ-LC13 were observed for dyspnea (54.4% of patients), cough (46.7%), and chest pain (38.9%), evident at cycle 2 and throughout treatment (least-squares mean [LSM] changes from baseline: dyspnea, -3.2 [p = 0.019]; cough, -9.3 [p < 0.001]; chest pain, -8.2 [p < 0.001]). EORTC QLQ-C30 results indicated no statistically significant changes in global health status/quality of life (LSM change from baseline: -1.8 [p = 0.235]). On symptom scores, significant worsening from baseline was observed for diarrhea (LSM change from baseline: +34.1; p < 0.001) and appetite loss (+6.6; p = 0.004), while improvements were observed for dyspnea (LSM change from baseline: -5.1 [p = 0.002]), insomnia (-6.5 [p = 0.001]), and constipation (-5.7 [p < 0.001]). EQ-5D-5L health status was maintained. Common PRO-CTCAE symptoms were diarrhea, dry skin, rash, and decreased appetite (mostly low grade); in the first 24 weeks of treatment, 64.4% of patients had worsening diarrhea frequency and 67.8% had worsening dry skin severity. Overall, PROs with mobocertinib showed clinically meaningful improvement in lung cancer-related symptoms, with health-related quality of life maintained despite changes in some adverse event symptom scales.
Insights
Mobocertinib improved lung cancer symptoms like dyspnea and cough in patients with EGFR exon 20 insertion+ NSCLC. Health-related quality of life was maintained, despite some adverse event symptom worsening.
Area of Science:
- Oncology
- Pharmacology
- Patient-Reported Outcomes
Background:
- Epidermal growth factor receptor (EGFR) exon 20 insertions (ex20ins) confer resistance to approved EGFR tyrosine kinase inhibitors (TKIs).
- Mobocertinib is an oral, first-in-class TKI targeting EGFR ex20ins.
- Previous studies demonstrated mobocertinib's efficacy in previously treated EGFR ex20ins+ metastatic non-small cell lung cancer (mNSCLC).
Purpose of the Study:
- To assess patient-reported outcomes (PROs) including quality of life and symptom burden with mobocertinib in patients with EGFR ex20ins+ mNSCLC.
- To evaluate the impact of mobocertinib on lung cancer-specific symptoms and global health status.
Main Methods:
- The EXCLAIM extension cohort (N=90) assessed PROs using EORTC QLQ-C30, QLQ-LC13, EQ-5D-5L, and PRO-CTCAE questionnaires.
- Mobocertinib was administered at 160 mg once daily over 28-day cycles.
- Data cutoff was November 1, 2020, with a median follow-up of 13.0 months.
Main Results:
- Clinically meaningful improvements were observed in lung cancer symptoms: dyspnea (54.4%), cough (46.7%), and chest pain (38.9%).
- No statistically significant changes in global health status/quality of life were noted (EORTC QLQ-C30).
- Worsening symptoms included diarrhea (+34.1) and appetite loss (+6.6), while improvements were seen in dyspnea (-5.1), insomnia (-6.5), and constipation (-5.7).
Conclusions:
- Mobocertinib demonstrated clinically meaningful improvements in key lung cancer symptoms.
- Health-related quality of life was generally maintained throughout treatment.
- PROs provide valuable insights into the patient experience with mobocertinib in EGFR ex20ins+ mNSCLC.
