Trial Outcomes & Findings for Study With Gefitinib in Combination With Olaparib (AZD2281) Versus Gefitinib Alone (NCT NCT01513174)

Last Updated: 2024-06-28

Results Overview

Defined as the length of time from the date of randomization to the date of the first documented progression of disease. "Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions"

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

186 participants

Primary outcome timeframe

From the date of randomization until end of follow up, up to 30 months.

Results posted on

2024-06-28

Participant Flow

Participant milestones

Participant milestones
Measure	Control Gefitinib Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression	Experimental: Gefitinib in Combination With Olaparib Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase I study) twice a day, continuously, in 28-day cycles. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression Olaparib: Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase Ib study) twice a day, continuously, in 28-day cycles.
Overall Study STARTED	94	92
Overall Study COMPLETED	90	84
Overall Study NOT COMPLETED	4	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Control Gefitinib Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression	Experimental: Gefitinib in Combination With Olaparib Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase I study) twice a day, continuously, in 28-day cycles. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression Olaparib: Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase Ib study) twice a day, continuously, in 28-day cycles.
Overall Study Inclusion Error	1	7
Overall Study Not receive study treatment	3	1

Baseline Characteristics

Study With Gefitinib in Combination With Olaparib (AZD2281) Versus Gefitinib Alone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control Gefitinib n=91 Participants Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression	Experimental: Gefitinib in Combination With Olaparib n=91 Participants Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase I study) twice a day, continuously, in 28-day cycles. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression Olaparib: Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase Ib study) twice a day, continuously, in 28-day cycles.	Total n=182 Participants Total of all reporting groups
Age, Continuous	65.97 years STANDARD_DEVIATION 11.29 • n=5 Participants	63.40 years STANDARD_DEVIATION 11.39 • n=7 Participants	65.95 years STANDARD_DEVIATION 11.29 • n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	66 Participants n=7 Participants	123 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	25 Participants n=7 Participants	59 Participants n=5 Participants
Region of Enrollment Spain	81 participants n=5 Participants	78 participants n=7 Participants	159 participants n=5 Participants
Region of Enrollment Mexico	10 participants n=5 Participants	13 participants n=7 Participants	23 participants n=5 Participants
Smoking status Smoker	4 participants n=5 Participants	10 participants n=7 Participants	14 participants n=5 Participants
Smoking status Former smoker	27 participants n=5 Participants	26 participants n=7 Participants	53 participants n=5 Participants
Smoking status Never smoker	60 participants n=5 Participants	55 participants n=7 Participants	115 participants n=5 Participants
ECOG Performance Status Scale ECOG 0	25 participants n=5 Participants	24 participants n=7 Participants	49 participants n=5 Participants
ECOG Performance Status Scale ECOG 1	59 participants n=5 Participants	59 participants n=7 Participants	118 participants n=5 Participants
ECOG Performance Status Scale ECOG 2	7 participants n=5 Participants	8 participants n=7 Participants	15 participants n=5 Participants
Bone metastasis Yes	25 participants n=5 Participants	30 participants n=7 Participants	55 participants n=5 Participants
Bone metastasis No	66 participants n=5 Participants	61 participants n=7 Participants	127 participants n=5 Participants
CNS metastasis Yes	11 participants n=5 Participants	10 participants n=7 Participants	21 participants n=5 Participants
CNS metastasis No	80 participants n=5 Participants	81 participants n=7 Participants	161 participants n=5 Participants
EGFR mutation EGFR exon 18	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
EGFR mutation EGFR exon 20	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
EGFR mutation Exon 21 L858R	35 participants n=5 Participants	25 participants n=7 Participants	60 participants n=5 Participants
EGFR mutation del 19	52 participants n=5 Participants	57 participants n=7 Participants	109 participants n=5 Participants
EGFR mutation UK	0 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization until end of follow up, up to 30 months.

Population: The PFS analysis is performed on the PP population

Outcome measures

Outcome measures
Measure	Control Gefitinib n=90 Participants Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression	Experimental: Gefitinib in Combination With Olaparib n=84 Participants Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase I study) twice a day, continuously, in 28-day cycles. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression Olaparib: Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase Ib study) twice a day, continuously, in 28-day cycles.
Progression-free Survival (PFS)	10.9 Month Interval 9.3 to 13.3	10.9 Month Interval 8.6 to 13.4

SECONDARY outcome

Timeframe: From the date of randomization until end of follow up, up to 30 months

Population: The OS analysis is performed on the mITT population.

Defined as the length of time from either the date of diagnosis or the start of the treatment that patients diagnosed with the disease are still alive.

Outcome measures

Outcome measures
Measure	Control Gefitinib n=91 Participants Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression	Experimental: Gefitinib in Combination With Olaparib n=91 Participants Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase I study) twice a day, continuously, in 28-day cycles. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression Olaparib: Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase Ib study) twice a day, continuously, in 28-day cycles.
Overall Survival	23.1 Month Interval 19.1 to 28.5	23.3 Month Interval 16.2 to 26.4

SECONDARY outcome

Timeframe: From the date of randomization until end of follow up, up to 30 months

To evaluate the best global response of the treatment as measured by investigator-assessed overall response rate (ORR) according to RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Outcome measures

Outcome measures
Measure	Control Gefitinib n=91 Participants Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression	Experimental: Gefitinib in Combination With Olaparib n=91 Participants Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase I study) twice a day, continuously, in 28-day cycles. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression Olaparib: Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase Ib study) twice a day, continuously, in 28-day cycles.
Best Global Response During Treatment Period Not evaluable	3 participants	11 participants
Best Global Response During Treatment Period Complete Response	2 participants	1 participants
Best Global Response During Treatment Period Partial Response	59 participants	59 participants
Best Global Response During Treatment Period Stable disease	21 participants	12 participants
Best Global Response During Treatment Period Progressive Disease	6 participants	8 participants

Adverse Events

Control Gefitinib

Serious events: 39 serious events

Other events: 88 other events

Deaths: 10 deaths

Experimental: Gefitinib in Combination With Olaparib

Serious events: 22 serious events

Other events: 90 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Eva Pereira

Fundación GECP

Phone: +34 934302006

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Control Gefitinib n=91 participants at risk Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression	Experimental: Gefitinib in Combination With Olaparib n=91 participants at risk Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase I study) twice a day, continuously, in 28-day cycles. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression Olaparib: Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase Ib study) twice a day, continuously, in 28-day cycles.
Vascular disorders Hypertension	2.2% 2/91 • Number of events 2 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Cardiac disorders Pericardial effusion	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Other - Respiratory, Thoracic And Mediastinal Disorders	11.0% 10/91 • Number of events 10 • 37 months The severity of AE will be determined using CTCAE version 4.0.	12.1% 11/91 • Number of events 11 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Pneumonia	2.2% 2/91 • Number of events 2 • 37 months The severity of AE will be determined using CTCAE version 4.0.	2.2% 2/91 • Number of events 2 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Blood and lymphatic system disorders Anemia	11.0% 10/91 • Number of events 10 • 37 months The severity of AE will be determined using CTCAE version 4.0.	17.6% 16/91 • Number of events 16 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Blood and lymphatic system disorders Bone marrow aplastic	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Nervous system disorders Cerebral infart subjects affected	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
General disorders Edema Limbs	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Gastrointestinal disorders Diarrhea	2.2% 2/91 • Number of events 2 • 37 months The severity of AE will be determined using CTCAE version 4.0.	3.3% 3/91 • Number of events 3 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Gastrointestinal disorders Mucositis oral	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Gastrointestinal disorders Constipation	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Gastrointestinal disorders Gastrointestinal infection	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Renal and urinary disorders Renal insuficiency	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Skin and subcutaneous tissue disorders Rash acneiform	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Musculoskeletal and connective tissue disorders Pain	2.2% 2/91 • Number of events 2 • 37 months The severity of AE will be determined using CTCAE version 4.0.	3.3% 3/91 • Number of events 3 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Musculoskeletal and connective tissue disorders Asthralgia	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.	1.1% 1/91 • Number of events 1 • 37 months The severity of AE will be determined using CTCAE version 4.0.

Measure	Control Gefitinib n=91 participants at risk Gefitinib will be administered once daily, continuously, in 28-day cycles, as a fixed dose of 250 mg/day. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression	Experimental: Gefitinib in Combination With Olaparib n=91 participants at risk Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase I study) twice a day, continuously, in 28-day cycles. Gefitinib: Gefitinib 250 mg once a day, continuously, in 28-day cycles, until progression Olaparib: Gefitinib 250 mg once a day, in combination with olaparib (at the recommended dose in the previous Phase Ib study) twice a day, continuously, in 28-day cycles.
Investigations Alanine aminotransferase increased	30.8% 28/91 • Number of events 28 • 37 months The severity of AE will be determined using CTCAE version 4.0.	15.4% 14/91 • Number of events 14 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Investigations GGT increase	19.8% 18/91 • Number of events 18 • 37 months The severity of AE will be determined using CTCAE version 4.0.	16.5% 15/91 • Number of events 15 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Investigations Alkaline Phosphatase Increased	17.6% 16/91 • Number of events 16 • 37 months The severity of AE will be determined using CTCAE version 4.0.	17.6% 16/91 • Number of events 16 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Investigations Aspartate aminotransferase increased	22.0% 20/91 • Number of events 20 • 37 months The severity of AE will be determined using CTCAE version 4.0.	11.0% 10/91 • Number of events 10 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Investigations Lipasa increased	7.7% 7/91 • Number of events 7 • 37 months The severity of AE will be determined using CTCAE version 4.0.	4.4% 4/91 • Number of events 4 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Cough	40.7% 37/91 • Number of events 37 • 37 months The severity of AE will be determined using CTCAE version 4.0.	31.9% 29/91 • Number of events 29 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Flu like symptoms	15.4% 14/91 • Number of events 14 • 37 months The severity of AE will be determined using CTCAE version 4.0.	5.5% 5/91 • Number of events 5 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Bronchial infection	5.5% 5/91 • Number of events 5 • 37 months The severity of AE will be determined using CTCAE version 4.0.	0.00% 0/91 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Nervous system disorders Dysgeusia	6.6% 6/91 • Number of events 6 • 37 months The severity of AE will be determined using CTCAE version 4.0.	15.4% 14/91 • Number of events 14 • 37 months The severity of AE will be determined using CTCAE version 4.0.
General disorders Fatigue	54.9% 50/91 • Number of events 50 • 37 months The severity of AE will be determined using CTCAE version 4.0.	50.5% 46/91 • Number of events 46 • 37 months The severity of AE will be determined using CTCAE version 4.0.
General disorders Fever	12.1% 11/91 • Number of events 11 • 37 months The severity of AE will be determined using CTCAE version 4.0.	6.6% 6/91 • Number of events 6 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Gastrointestinal disorders Nausea	25.3% 23/91 • Number of events 23 • 37 months The severity of AE will be determined using CTCAE version 4.0.	56.0% 51/91 • Number of events 51 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Gastrointestinal disorders Vomiting	18.7% 17/91 • Number of events 17 • 37 months The severity of AE will be determined using CTCAE version 4.0.	37.4% 34/91 • Number of events 34 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Renal and urinary disorders Urinary tract infection	15.4% 14/91 • Number of events 14 • 37 months The severity of AE will be determined using CTCAE version 4.0.	12.1% 11/91 • Number of events 11 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Skin and subcutaneous tissue disorders Dry skin	23.1% 21/91 • Number of events 21 • 37 months The severity of AE will be determined using CTCAE version 4.0.	19.8% 18/91 • Number of events 18 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Skin and subcutaneous tissue disorders Alopecia	13.2% 12/91 • Number of events 12 • 37 months The severity of AE will be determined using CTCAE version 4.0.	13.2% 12/91 • Number of events 12 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Skin and subcutaneous tissue disorders Pruritus	12.1% 11/91 • Number of events 11 • 37 months The severity of AE will be determined using CTCAE version 4.0.	14.3% 13/91 • Number of events 13 • 37 months The severity of AE will be determined using CTCAE version 4.0.
General disorders Anorexia	27.5% 25/91 • Number of events 25 • 37 months The severity of AE will be determined using CTCAE version 4.0.	44.0% 40/91 • Number of events 40 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Infections and infestations Paronychia	16.5% 15/91 • Number of events 15 • 37 months The severity of AE will be determined using CTCAE version 4.0.	7.7% 7/91 • Number of events 7 • 37 months The severity of AE will be determined using CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	11.0% 10/91 • Number of events 10 • 37 months The severity of AE will be determined using CTCAE version 4.0.	4.4% 4/91 • Number of events 4 • 37 months The severity of AE will be determined using CTCAE version 4.0.