Trial Outcomes & Findings for A Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations (NCT NCT02588261)

Last Updated: 2024-12-10

Results Overview

PFS was defined as the time from the date of randomization until the date of radiological disease progression or until death due to any cause, based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by IRR. Results are based Kaplan-Meier estimate. If a participant had neither progressed nor died, who received any further anticancer therapy for the disease before radiological progression, the participant was censored at the date of last radiological assessment. If progression or death occurred after missing 2 scheduled radiological assessments, the participant was censored at the date of last radiological assessment or at the date of randomization if no post-baseline radiological assessment was available.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

530 participants

Primary outcome timeframe

From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)

Results posted on

2024-12-10

Participant Flow

First-line participants with locally advanced, metastatic or unresectable stage IIIB/IV adenocarcinoma NSCLC with EGFR activating mutation (exon 19 deletion or exon 21 L858R) with or without a T790M mutation who had not previously been treated with an EGFR inhibitors were enrolled in 201 sites in 23 countries.

Eligible participants were stratified according to the following: Eastern Cooperative Oncology Group (ECOG) performance status (0, 1 or 2), Epidermal growth factor receptor (EGFR) mutation status (exon 19 deletion or mutations in exon 21 \[L858R\]), Tyrosine kinase inhibitor (TKI) chosen (erlotinib or gefitinib) and race (Asian versus non-Asian).

Participant milestones

Participant milestones
Measure	ASP8273 Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Overall Study STARTED	267	263
Overall Study Treated	265	262
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	267	263

Reasons for withdrawal

Reasons for withdrawal
Measure	ASP8273 Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Overall Study Study Terminated by Sponsor	157	142
Overall Study Protocol Deviation	1	0
Overall Study Death	1	2
Overall Study Withdrawal by Subject	12	8
Overall Study Noncompliance with Study Drug	0	1
Overall Study Miscellaneous	5	4
Overall Study Progressive Disease	61	82
Overall Study Adverse Event	29	24
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

A Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ASP8273 n=267 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=263 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Total n=530 Participants Total of all reporting groups
Age, Continuous	66.6 Years STANDARD_DEVIATION 10.6 • n=5 Participants	65.0 Years STANDARD_DEVIATION 11.5 • n=7 Participants	65.8 Years STANDARD_DEVIATION 11.1 • n=5 Participants
Sex: Female, Male Female	171 Participants n=5 Participants	153 Participants n=7 Participants	324 Participants n=5 Participants
Sex: Female, Male Male	96 Participants n=5 Participants	110 Participants n=7 Participants	206 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	244 Participants n=5 Participants	245 Participants n=7 Participants	489 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized White	89 Participants n=5 Participants	88 Participants n=7 Participants	177 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	162 Participants n=5 Participants	163 Participants n=7 Participants	325 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Missing	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Investigator Prerandomization Selected TKI at Randomization Erlotinib	153 Participants n=5 Participants	151 Participants n=7 Participants	304 Participants n=5 Participants
Investigator Prerandomization Selected TKI at Randomization Gefitinib	114 Participants n=5 Participants	112 Participants n=7 Participants	226 Participants n=5 Participants
ECOG Performance Status at Randomization Grade 0	103 Participants n=5 Participants	103 Participants n=7 Participants	206 Participants n=5 Participants
ECOG Performance Status at Randomization Grade 1	155 Participants n=5 Participants	152 Participants n=7 Participants	307 Participants n=5 Participants
ECOG Performance Status at Randomization Grade 2	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
EGFR Mutation Status at Randomization Exon 19 Deletion	149 Participants n=5 Participants	147 Participants n=7 Participants	296 Participants n=5 Participants
EGFR Mutation Status at Randomization Exon 21 L858R	118 Participants n=5 Participants	116 Participants n=7 Participants	234 Participants n=5 Participants
Race (Asian vs Non-Asian) at Randomization Asian	163 Participants n=5 Participants	162 Participants n=7 Participants	325 Participants n=5 Participants
Race (Asian vs Non-Asian) at Randomization Non-Asian	104 Participants n=5 Participants	101 Participants n=7 Participants	205 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)

Population: The analysis population was the full analysis set (FAS), which consisted of all participants who were randomized.

Outcome measures

Outcome measures
Measure	ASP8273 n=267 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=263 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Progression Free Survival (PFS) as Assessed by Independent Radiologic Review (IRR)	9.26 months Interval 5.62 to 11.07	9.59 months Interval 8.77 to Data could not be calculated due to low number of events.

SECONDARY outcome

Timeframe: From date of randomization up to data cut-off date 21 Dec 2017 (approximately 22 months)

Population: The analysis population was the safety analysis set (SAF), which consisted of all participants who took at least one dose of study drug.

All events of death after the first study drug administration were included.

Outcome measures

Outcome measures
Measure	ASP8273 n=265 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=262 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Percentage of Deaths	14.7 percentage of participants	13.4 percentage of participants

SECONDARY outcome

Timeframe: From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)

Population: The analysis population was the FAS.

Percentage of participants with OR was defined as the proportion of participants with best overall response as complete response (CR) or partial response (PR) without confirmation based on the RECIST v1.1 as assessed by the blinded IRR. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	ASP8273 n=267 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=263 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Percentage of Participants With Objective Response (OR)	33.0 percentage of participants Interval 27.4 to 39.0	47.9 percentage of participants Interval 41.7 to 54.1

SECONDARY outcome

Timeframe: From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)

Population: The analysis population was the FAS.

PFS was defined as the time from the date of randomization until the date of radiological disease progression or until death due to any cause, based on RECIST V1.1, as assessed by local investigator. Results are based Kaplan-Meier estimate. If a participant had neither progressed nor died, who received any further anticancer therapy for the disease before radiological progression, the participant was censored at the date of last radiological assessment. If progression or death occurred after missing 2 scheduled radiological assessments, the participant was censored at the date of last radiological assessment or at the date of randomization if no post-baseline radiological assessment was available.

Outcome measures

Outcome measures
Measure	ASP8273 n=267 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=263 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
PFS as Assessed by the Investigator	7.43 months Interval 5.49 to 9.26	10.12 months Interval 9.03 to Data could not be calculated due to low number of events.

SECONDARY outcome

Timeframe: From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)

Population: The analysis population was the FAS.

Percentage of participants with disease control was defined as the proportion of participants whose best overall response was rated as CR, PR or stable disease (SD) among all analyzed participants based on RECIST V1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug.

Outcome measures

Outcome measures
Measure	ASP8273 n=267 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=263 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Percentage of Participants With Disease Control	62.2 percentage of participants Interval 56.1 to 68.0	66.2 percentage of participants Interval 60.1 to 71.9

SECONDARY outcome

Timeframe: From date of first response up to data cut-off date 09 May 2017 (approximately 15 months)

Population: The analysis population was the FAS. Only participants with best overall response as CR or PR (without confirmation) were included in the analysis.

DOR was defined as the time from the date of the first response CR/PR (whichever was first recorded) as assessed by IRR to the date of radiographical progression or date of censoring. If a participant had not progressed, the participant was censored at the date of last radiological assessment or at the date of first CR/PR if no post-baseline radiological assessment was available. Results are based Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	ASP8273 n=88 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=126 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Duration of Response (DOR)	9.17 months Interval 5.45 to Data could not be calculated due to low number of events.	9.03 months Interval 7.39 to Data could not be calculated due to low number of events.

SECONDARY outcome

Timeframe: From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 09 May 2017

Population: The analysis population was SAF.

Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug. AEs were considered serious (SAEs) if the AE resulted in death, was life threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization.

Outcome measures

Outcome measures
Measure	ASP8273 n=265 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=262 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Number of Participants With Adverse Events (AEs) TEAE	251 participants	261 participants
Number of Participants With Adverse Events (AEs) Drug-Related TEAE	235 participants	246 participants
Number of Participants With Adverse Events (AEs) Serious TEAE	84 participants	67 participants
Number of Participants With Adverse Events (AEs) Drug-Related Serious TEAE	46 participants	18 participants
Number of Participants With Adverse Events (AEs) TEAE Leading to Death	14 participants	17 participants
Number of Participants With Adverse Events (AEs) Drug-Related TEAE Leading to Death	1 participants	1 participants
Number of Participants With Adverse Events (AEs) TEAE Leading to Treatment Withdrawal	39 participants	28 participants
Number of Participants With Adverse Events (AEs) Drug-Related TEAE Leading to Treatment Withdrawal	27 participants	17 participants
Number of Participants With Adverse Events (AEs) TEAE Leading to Dose Reduction	51 participants	51 participants
Number of Participants With Adverse Events (AEs) Drug-Related TEAE Leading to Dose Reduction	51 participants	50 participants
Number of Participants With Adverse Events (AEs) TEAE Leading to Dose Interruption	95 participants	74 participants
Number of Participants With Adverse Events (AEs) Drug-Related TEAE Leading to Dose Interruption	83 participants	55 participants
Number of Participants With Adverse Events (AEs) Death	39 participants	35 participants

SECONDARY outcome

Timeframe: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

Population: The analysis population was the SAF, with available data.

ACT-EGFRI-18 is an 18-item Likert-scaled questionnaire, used to assess the effect of EGFR inhibitors on quality of life (QoL). The questionnaire is arranged in three HRQL dimensions: physical (seven items), social/emotional (six items), and functional well-being (five items). The response scores ranged from 0 to 4, and the response categories include "not at all", "a little bit", "somewhat", "quite a bit", and "very much." Negatively worded items (e.g., "My skin bleeds easily "or "My skin condition affects my mood") are reverse-scored, so that participants who experience a higher impact of symptom burden on HRQL receive a lower score (range 0-72).

Outcome measures

Outcome measures
Measure	ASP8273 n=248 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=251 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Functional Assessment of Cancer Therapy - EGFR Inhibitors Subscale (FACT-EGFRI-18) Questionnaire	2.79 units on a scale Standard Deviation 4.97	9.34 units on a scale Standard Deviation 10.57

SECONDARY outcome

Timeframe: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

Population: The analysis population was the SAF, with available data.

The EORTC-QLQ-LC13 is a validated module of the EORTC-QLQ-Core 30, which includes module items that evaluate symptoms such as cough, hemoptysis, shortness of breath, sore mouth or tongue, dysphagia, tingling hands or feet, hair loss and pain. The total score for the questionnaire ranges from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.

Outcome measures

Outcome measures
Measure	ASP8273 n=248 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=251 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC-QLQ-LC13)	18.93 units on a scale Standard Deviation 4.42	18.78 units on a scale Standard Deviation 4.69

SECONDARY outcome

Timeframe: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

Population: The analysis population was the SAF, with available data.

EORTC-QLQ-LC30 is a 30-item cancer-specific questionnaire with multitrait scaling was used to create five functional domain scales: Physical, Role, Emotional, Social and Cognitive; two items evaluate global QoL; in addition, three symptom scales assess Fatigue, Pain and Emesis; and six single items assess other symptoms. The total score ranges from 0 to 100, with a high score for a functional scale representing a high/healthy level of functioning and a high score for a symptom scale or item representing a high level of symptomatology or problems.

Outcome measures

Outcome measures
Measure	ASP8273 n=248 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=251 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30)	53.77 units on a scale Standard Deviation 11.49	52.01 units on a scale Standard Deviation 11.26

SECONDARY outcome

Timeframe: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

Population: The analysis population was the SAF, with available data.

The EQ-5D is a generic preference-based measure that indirectly measures the utility for health that generates an index-based summary score based upon societal preference weights. The EQ-5D-5L consists of 6 items that cover 5 main domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a general visual analog scale (VAS) for health status. Each item has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The VAS ranges from 0 (worst health status) and 100 (best health status).

Outcome measures

Outcome measures
Measure	ASP8273 n=248 Participants Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=251 Participants Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Mobility	1.78 Units on a scale Standard Deviation 0.96	1.48 Units on a scale Standard Deviation 0.85
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Self-care	1.28 Units on a scale Standard Deviation 0.68	1.19 Units on a scale Standard Deviation 0.60
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Usual Activities	1.71 Units on a scale Standard Deviation 0.94	1.54 Units on a scale Standard Deviation 0.83
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Pain/Discomfort	1.79 Units on a scale Standard Deviation 0.86	1.71 Units on a scale Standard Deviation 0.83
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Anxiety/Depression	1.61 Units on a scale Standard Deviation 0.77	1.54 Units on a scale Standard Deviation 0.76
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) VAS	69.44 Units on a scale Standard Deviation 19.17	72.36 Units on a scale Standard Deviation 17.19

Adverse Events

ASP8273

Serious events: 84 serious events

Other events: 240 other events

Deaths: 39 deaths

Erlotinib or Gefitinib

Serious events: 67 serious events

Other events: 253 other events

Deaths: 35 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Medical Director

Astellas Pharma Global Development, Inc.

Phone: 1800 888-7704

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the muli-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Publication restrictions are in place

Restriction type: OTHER

Measure	ASP8273 n=265 participants at risk Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).	Erlotinib or Gefitinib n=262 participants at risk Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Skin and subcutaneous tissue disorders Pruritus	4.5% 12/265 • Number of events 13 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	13.4% 35/262 • Number of events 44 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Blood and lymphatic system disorders Anaemia	7.9% 21/265 • Number of events 27 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	6.5% 17/262 • Number of events 30 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Eye disorders Dry eye	2.6% 7/265 • Number of events 8 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	6.5% 17/262 • Number of events 21 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Gastrointestinal disorders Constipation	20.4% 54/265 • Number of events 68 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	9.2% 24/262 • Number of events 24 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Gastrointestinal disorders Diarrhoea	60.8% 161/265 • Number of events 255 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	51.5% 135/262 • Number of events 224 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Gastrointestinal disorders Dry mouth	11.3% 30/265 • Number of events 31 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	0.38% 1/262 • Number of events 1 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Gastrointestinal disorders Nausea	24.9% 66/265 • Number of events 85 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	12.6% 33/262 • Number of events 41 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Gastrointestinal disorders Stomatitis	6.8% 18/265 • Number of events 21 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	21.0% 55/262 • Number of events 70 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Gastrointestinal disorders Vomiting	19.2% 51/265 • Number of events 60 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	9.9% 26/262 • Number of events 31 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
General disorders Asthenia	11.7% 31/265 • Number of events 39 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	7.3% 19/262 • Number of events 28 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
General disorders Fatigue	18.9% 50/265 • Number of events 73 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	11.5% 30/262 • Number of events 47 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
General disorders Pyrexia	6.8% 18/265 • Number of events 22 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	6.5% 17/262 • Number of events 20 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Infections and infestations Paronychia	1.9% 5/265 • Number of events 6 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	25.6% 67/262 • Number of events 106 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Infections and infestations Upper respiratory tract infection	3.8% 10/265 • Number of events 11 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	6.9% 18/262 • Number of events 24 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Investigations Alanine aminotransferase increased	20.0% 53/265 • Number of events 125 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	19.5% 51/262 • Number of events 107 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Investigations Aspartate aminotransferase increased	13.6% 36/265 • Number of events 67 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	16.4% 43/262 • Number of events 88 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Investigations Blood bilirubin increased	1.5% 4/265 • Number of events 4 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	5.7% 15/262 • Number of events 28 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Investigations Platelet count decreased	6.8% 18/265 • Number of events 25 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	1.1% 3/262 • Number of events 5 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Investigations Weight decreased	6.4% 17/265 • Number of events 17 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	8.0% 21/262 • Number of events 27 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Metabolism and nutrition disorders Decreased appetite	21.1% 56/265 • Number of events 73 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	18.3% 48/262 • Number of events 64 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Metabolism and nutrition disorders Hyponatraemia	24.2% 64/265 • Number of events 134 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	2.7% 7/262 • Number of events 13 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 14/265 • Number of events 16 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	2.7% 7/262 • Number of events 7 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Musculoskeletal and connective tissue disorders Back pain	5.3% 14/265 • Number of events 16 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	6.9% 18/262 • Number of events 22 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Nervous system disorders Dizziness	10.9% 29/265 • Number of events 29 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	4.2% 11/262 • Number of events 11 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Nervous system disorders Dysgeusia	11.3% 30/265 • Number of events 35 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	3.8% 10/262 • Number of events 10 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Nervous system disorders Headache	7.9% 21/265 • Number of events 25 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	8.8% 23/262 • Number of events 25 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Nervous system disorders Paraesthesia	7.2% 19/265 • Number of events 22 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	2.7% 7/262 • Number of events 7 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Nervous system disorders Peripheral sensory neuropathy	21.5% 57/265 • Number of events 76 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	0.76% 2/262 • Number of events 2 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Psychiatric disorders Insomnia	8.3% 22/265 • Number of events 24 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	6.5% 17/262 • Number of events 17 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Respiratory, thoracic and mediastinal disorders Cough	9.4% 25/265 • Number of events 28 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	11.5% 30/262 • Number of events 41 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.5% 20/265 • Number of events 25 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	6.1% 16/262 • Number of events 16 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	2.3% 6/265 • Number of events 6 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	5.7% 15/262 • Number of events 15 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Skin and subcutaneous tissue disorders Alopecia	3.0% 8/265 • Number of events 8 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	14.1% 37/262 • Number of events 42 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Skin and subcutaneous tissue disorders Drug eruption	12.1% 32/265 • Number of events 34 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	71.0% 186/262 • Number of events 377 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)
Skin and subcutaneous tissue disorders Dry skin	12.1% 32/265 • Number of events 33 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)	25.2% 66/262 • Number of events 83 • From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)