Mobocertinib Improves PROs in Previously Treated EGFR Exon 20+ NSCLC

In a phase 1/2 trial, the selective targeting of EGFR exon 20 insertion mutations with mobocertinib in patients with previously treated non–small cell lung cancer resulted in superior patient-reported outcomes.

Patients treated with mobocertinib (formerly TAK-788) for previously treated non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations as part of the EXCLAIM extension cohort demonstrated improvements in patient-reported outcomes (PROs), according to a poster presentation of the data made available as part of the 2021 World Conference on Lung Cancer.

In patients considered to have difficult-to-treat disease who were treated as part of a phase 1/2 trial (NCT02716116), superior PROs were evidenced by better core NSCLC symptoms within 2 months of treatment initiation which was maintained for the duration of therapy and was consistent with clinical activity.

“Overall health-related quality of life was maintained during therapy, despite the occurrence of adverse events such as rash and gastrointestinal-related symptoms,” Maria Rosario Garcia Campelo, MD, of the University Hospital A Coruña in Spain, said during a presentation of the data.

The objective of the current analysis was to evaluate PROs associated with daily oral mobocertinib at 160 mg daily in the discussed patient population. PRO tools used included the European Organisation for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (EORTC QLQ-C30) for cancer-related functions and symptoms, the European Organisation for Research and Treatment of Cancer Core Quality-of-Life Questionnaire lung cancer module (EORTC QLQ-LC13) for lung cancer–specific symptoms, the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) and visual analogue scale (VAS) for general health-related quality of life, and selected items from Patient-Reported Outcomes–Common Terminology Criteria for Adverse Events Questionnaire (PRO-CTCAE) to assess symptomatic toxicity in these patients. Questionnaires were given prior to clinical evaluation or procedures at baseline, at select visits, and at 30 days following the last dose of treatment.

Compliance rates were above 80% for all instruments and were often above 90% for most cycles. At the data cutoff of November 1, 2020, 25 out of 96 patients (26%) remained on treatment with mobocertinib for a median time of treatment of 6.8 months (range, 0.0-18.8). Median patient age was 59 years (range, 27-80), with most patients being women (65%) and never smokers (73%) and the majority having adenocarcinoma histology (99%) and an ECOG performance status of 1 (71%). The median number of prior therapies was 1, with prior platinum-based chemotherapy accounting for 90% of patients, prior immunotherapy in 34%, and prior EGFR inhibitors in 31%. Baseline brain metastases were present in 34% of patients.

Clinically meaningful lung cancer symptom improvement by EORTC QLQ-LC13 was defined as a 10-point or greater decrease in symptom score. At a median follow-up of 13.0 months (range, 0.7-18.8), clinically meaningful changes in dyspnea occurred in 54.4% of patients, with a mean change to baseline symptoms of –3.2 (P = .019). Cough improved in 46.7% of patients with a mean baseline improvement of –9.3 (P < .001). For chest pain, improvement occurred in 38.9% of patients with a mean baseline improvement of –8.2 (P < .001). In over 50% of the patients examined, dyspnea, cough, and chest pain were improved or stable throughout the study.

By EORTC QLQ-C30, baseline scores were maintained or improved in most patients treated with mobocertinib, for a least square mean change of –1.8 (95% CI, –4.8 to 1.2; P = .235). By PRO-CTCAE, the majority of adverse effects of were not categorized in the 2 highest categories of “severe” or “very severe”, with only diarrhea and dry skin escalating to above 10% of events being in the highest categories (22.2% and 11.1%, respectively). By EQ-5D VAS, patient-reported general health-related quality of life remained largely stable during treatment. 

Previously reported data from the trial demonstrated efficacy of mobocertinib in this patient population, with a confirmed overall response rate of 28% (95% CI, 20%-37%), a median overall survival of 24.0 months (95% CI, 14.6-28.8), and a median progression-free survival was 7.3 months (95% CI, 5.5-9.2). The mechanism of action of mobocertinib is unique in that it selectively targets exon 20 insertion mutations in EGFR

“Exon 20 insertion mutations account for up to 12% of NSCLC tumors with EGFR mutations. Most of these patients are treated in the first line with platinum-based chemotherapy, but their disease, unfortunately, progresses very rapidly,” Campelo said. Use of mobocertinib in these patients may fulfill an unmet clinical need.


Garcia Campelo MR, Zhou C, Ramalingam SS, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion+ metastatic NSCLC: patient-reported outcomes from EXCLAIM extension cohort. Presented at: 2021 World Conference on Lung Cancer; September 8-14, 2021. Virtual. Abstract FP09.02.

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