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

Maria Rosario Garcia Campelo; Caicun Zhou; Suresh S Ramalingam; Huamao M Lin; Tae Min Kim; Gregory J Riely; Tarek Mekhail; Danny Nguyen; Erin Goodman; Minal Mehta; Sanjay Popat; Pasi A Jänne

doi:10.3390/jcm12010112

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

J Clin Med. 2022 Dec 23;12(1):112. doi: 10.3390/jcm12010112.

Authors

Maria Rosario Garcia Campelo¹, Caicun Zhou², Suresh S Ramalingam³, Huamao M Lin⁴, Tae Min Kim⁵, Gregory J Riely⁶, Tarek Mekhail⁷, Danny Nguyen⁸, Erin Goodman⁴, Minal Mehta⁴, Sanjay Popat^{9

10}, Pasi A Jänne^{11

12}

Affiliations

¹ Department of Medical Oncology, University Hospital Complex A Coruña, 15006 A Coruña, Spain.
² Department of Oncology, Shanghai Pulmonary Hospital, Shanghai 200433, China.
³ Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
⁴ Takeda Development Center Americas, Inc., Lexington, MA 02421, USA.
⁵ Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea.
⁶ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁷ Advent Health Orlando, Orlando, FL 32803, USA.
⁸ Pacific Shores Medical Group, Long Beach, CA 90813, USA.
⁹ Lung Unit, The Royal Marsden Hospital, London SW3 6JJ, UK.
¹⁰ The Institute of Cancer Research, University of London, London SM2 5NG, UK.
¹¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹² Harvard Medical School, Boston, MA 02215, USA.

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.

Keywords: carcinoma; lung neoplasms; mutation; neoplasm metastasis; non-small cell lung; quality of life.

Abstract

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