Mobocertinib (TAK-788) in Exon 20 Insertion+ Metastatic NSCLC: Patient-Reported Outcomes from EXCLAIM Extension Cohort.

Mobocertinib, an oral, first-in-class epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for exon 20 insertions (ex20ins), achieved durable responses in adults with previously treated 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 [ = 0.019]; cough, -9.3 [ < 0.001]; chest pain, -8.2 [ < 0.001]). EORTC QLQ-C30 results indicated no statistically significant changes in global health status/quality of life (LSM change from baseline: -1.8 [ = 0.235]). On symptom scores, significant worsening from baseline was observed for diarrhea (LSM change from baseline: +34.1; < 0.001) and appetite loss (+6.6; = 0.004), while improvements were observed for dyspnea (LSM change from baseline: -5.1 [ = 0.002]), insomnia (-6.5 [ = 0.001]), and constipation (-5.7 [ 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.