Trial Outcomes & Findings for Study to Evaluate Treatment Customized According to RAP80 and BRCA1 in Patients With Advanced Lung Carcinoma (NCT NCT00617656)

Last Updated: 2024-01-30

Results Overview

Defined as the length of time from the start of treatment 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

TERMINATED

Study phase

PHASE3

Target enrollment

382 participants

Primary outcome timeframe

From the day of start of treatment until first documented progression or death due to any cause,up to 18 months.

Results posted on

2024-01-30

Participant Flow

There has been a total screening of 1161 patients from which a total of 382 patients could finally be included and randomized.

Participant milestones

Participant milestones
Measure	A Control Group Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6 Cisplatin, Docetaxel: Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6	Experimental Group Arm B1 Patients with low expression of RAP 80, and with any level of BRCA1 expression: gemcitabine 1250 mg/m2, days 1 and 8, and cisplatin 75 mg/m2, day 1. Cycles every 21 days.	Experimental Group Arm B2 Patients with intermediate or high expression of RAP 80, and with low or intermediate expression of BRCA1: docetaxel 75 mg/m2, and cisplatin 75 mg/m2, both administered on day 1, every 21 days	Experimental Group Arm B3 Patients with intermediate or high expression of RAP 80, and with high expression of BRCA1: docetaxel 75 mg/m2, day 1. Cycles every 21 days.
Overall Study STARTED	190	81	62	49
Overall Study COMPLETED	142	45	49	43
Overall Study NOT COMPLETED	48	36	13	6

Reasons for withdrawal

Reasons for withdrawal
Measure	A Control Group Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6 Cisplatin, Docetaxel: Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6	Experimental Group Arm B1 Patients with low expression of RAP 80, and with any level of BRCA1 expression: gemcitabine 1250 mg/m2, days 1 and 8, and cisplatin 75 mg/m2, day 1. Cycles every 21 days.	Experimental Group Arm B2 Patients with intermediate or high expression of RAP 80, and with low or intermediate expression of BRCA1: docetaxel 75 mg/m2, and cisplatin 75 mg/m2, both administered on day 1, every 21 days	Experimental Group Arm B3 Patients with intermediate or high expression of RAP 80, and with high expression of BRCA1: docetaxel 75 mg/m2, day 1. Cycles every 21 days.
Overall Study Inclusion error	4	4	0	0
Overall Study Missing data	44	30	13	6
Overall Study Withdrawal by Subject	0	2	0	0

Baseline Characteristics

Study to Evaluate Treatment Customized According to RAP80 and BRCA1 in Patients With Advanced Lung Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A Control Group n=142 Participants Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6 Cisplatin, Docetaxel: Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6	Experimental Group n=137 Participants Include experimental groups Arm B1+ Arm B2+ Arm B3	Total n=279 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	63 years n=7 Participants	62.5 years n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	19 Participants n=7 Participants	52 Participants n=5 Participants
Sex: Female, Male Male	109 Participants n=5 Participants	118 Participants n=7 Participants	227 Participants n=5 Participants
Region of Enrollment Spain	142 participants n=5 Participants	137 participants n=7 Participants	279 participants n=5 Participants
Smoking status Smoker	38 participants n=5 Participants	36 participants n=7 Participants	74 participants n=5 Participants
Smoking status Non-smoker	97 participants n=5 Participants	95 participants n=7 Participants	192 participants n=5 Participants
Smoking status No data	7 participants n=5 Participants	6 participants n=7 Participants	13 participants n=5 Participants
ECOG ECOG 0	44 participants n=5 Participants	49 participants n=7 Participants	93 participants n=5 Participants
ECOG ECOG 1-2	98 participants n=5 Participants	88 participants n=7 Participants	186 participants n=5 Participants
Stage IV disease extension at study entrance Thoracic	16 participants n=5 Participants	12 participants n=7 Participants	28 participants n=5 Participants
Stage IV disease extension at study entrance Extra-thoracic	124 participants n=5 Participants	123 participants n=7 Participants	247 participants n=5 Participants
Stage IV disease extension at study entrance No data	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Histology Squamous	50 participants n=5 Participants	49 participants n=7 Participants	99 participants n=5 Participants
Histology NonSquamous	92 participants n=5 Participants	88 participants n=7 Participants	180 participants n=5 Participants
Median number of cycles	5 cycles n=5 Participants	4 cycles n=7 Participants	4.5 cycles n=5 Participants
BRCA1 mRNA level Low BRCA mRNA level	50 participants n=5 Participants	48 participants n=7 Participants	98 participants n=5 Participants
BRCA1 mRNA level Intermediate BRCA mRNA level	46 participants n=5 Participants	42 participants n=7 Participants	88 participants n=5 Participants
BRCA1 mRNA level Hight BRCA mRNA level	46 participants n=5 Participants	47 participants n=7 Participants	93 participants n=5 Participants
RAP 80 mRNA level Low RAP80 mRNA level	52 participants n=5 Participants	48 participants n=7 Participants	100 participants n=5 Participants
RAP 80 mRNA level Intermediate RAP80 mRNA level	50 participants n=5 Participants	55 participants n=7 Participants	105 participants n=5 Participants
RAP 80 mRNA level Hight RAP80 mRNA level	36 participants n=5 Participants	34 participants n=7 Participants	70 participants n=5 Participants
RAP 80 mRNA level Undetermined level RAP80 mRNA	4 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants
mRNA RAP80 expression values	1.65 fg/μg n=5 Participants	1.74 fg/μg n=7 Participants	1.7 fg/μg n=5 Participants
mRNA BRCA1 expression values	11.86 fg/μg n=5 Participants	12.28 fg/μg n=7 Participants	12 fg/μg n=5 Participants

PRIMARY outcome

Timeframe: From the day of start of treatment until first documented progression or death due to any cause,up to 18 months.

Outcome measures

Outcome measures
Measure	Control Group n=142 Participants Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6 Cisplatin, Docetaxel: Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6	B1: Experimental Group 1 n=45 Participants Low RAP expression and any levels of BRCA1 expression: Gemcitabine 1250 mg/m2, days 1 and 8, and Cisplatin 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6 Gemcitabine, Cisplatin: Gemcitabine 1250 mg/m2, days 1 and 8, and Cisplatin 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6	B2 Experimental Group 2 n=49 Participants Intermediate or high RAP expression and low or intermediate BRCA1 expression: Docetaxel 75 mg/m2 and Cisplatin 75 mg/m2, both administered on day 1, every 21 days. Total number of cycles: 6 Docetaxel, Cisplatin: Docetaxel 75 mg/m2 and Cisplatin 75 mg/m2, both administered on day 1, every 21 days. Total number of cycles: 6	B3 Experimental Group 3 n=43 Participants Intermediate or high RAP expression and high BRCA1 expression: Docetaxel 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6 Docetaxel: Docetaxel 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6
Progression Free Survival	5.49 Month Interval 5.08 to 5.91	5.43 Month Interval 5.08 to 5.77	5.49 Month Interval 3.83 to 7.16	2.50 Month Interval 1.16 to 3.84

SECONDARY outcome

Timeframe: From the date of start of the treatment until death or end of follow up, up to 18 months.

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

Outcome measures

Outcome measures
Measure	Control Group n=142 Participants Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6 Cisplatin, Docetaxel: Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6	B1: Experimental Group 1 n=137 Participants Low RAP expression and any levels of BRCA1 expression: Gemcitabine 1250 mg/m2, days 1 and 8, and Cisplatin 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6 Gemcitabine, Cisplatin: Gemcitabine 1250 mg/m2, days 1 and 8, and Cisplatin 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6	B2 Experimental Group 2 Intermediate or high RAP expression and low or intermediate BRCA1 expression: Docetaxel 75 mg/m2 and Cisplatin 75 mg/m2, both administered on day 1, every 21 days. Total number of cycles: 6 Docetaxel, Cisplatin: Docetaxel 75 mg/m2 and Cisplatin 75 mg/m2, both administered on day 1, every 21 days. Total number of cycles: 6	B3 Experimental Group 3 Intermediate or high RAP expression and high BRCA1 expression: Docetaxel 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6 Docetaxel: Docetaxel 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6
Overall Survival	12.66 Month Interval 10.07 to 15.26	8.52 Month Interval 6.41 to 10.63	—	—

Adverse Events

Control Group

Serious events: 9 serious events

Other events: 0 other events

Deaths: 2 deaths

B1: Experimental Group 1

Serious events: 29 serious events

Other events: 0 other events

Deaths: 7 deaths

B2 Experimental Group 2

Serious events: 49 serious events

Other events: 0 other events

Deaths: 19 deaths

B3 Experimental Group 3

Serious events: 6 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

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

Serious adverse events
Measure	Control Group n=142 participants at risk Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6 Cisplatin, Docetaxel: Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6	B1: Experimental Group 1 n=45 participants at risk Low RAP expression and any levels of BRCA1 expression: Gemcitabine 1250 mg/m2, days 1 and 8, and Cisplatin 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6 Gemcitabine, Cisplatin: Gemcitabine 1250 mg/m2, days 1 and 8, and Cisplatin 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6	B2 Experimental Group 2 n=49 participants at risk Intermediate or high RAP expression and low or intermediate BRCA1 expression: Docetaxel 75 mg/m2 and Cisplatin 75 mg/m2, both administered on day 1, every 21 days. Total number of cycles: 6 Docetaxel, Cisplatin: Docetaxel 75 mg/m2 and Cisplatin 75 mg/m2, both administered on day 1, every 21 days. Total number of cycles: 6	B3 Experimental Group 3 n=43 participants at risk Intermediate or high RAP expression and high BRCA1 expression: Docetaxel 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6 Docetaxel: Docetaxel 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6
Blood and lymphatic system disorders Neutropenia	0.70% 1/142 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	6.7% 3/45 • Number of events 3 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	49.0% 24/49 • Number of events 24 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.3% 1/43 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Vascular disorders Tromboembolismo pulmonar	0.00% 0/142 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	6.7% 3/45 • Number of events 3 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	6.1% 3/49 • Number of events 3 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/43 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
General disorders Pain	0.00% 0/142 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	4.4% 2/45 • Number of events 2 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	4.1% 2/49 • Number of events 2 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/43 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Respiratory, thoracic and mediastinal disorders Respiratory infection	0.70% 1/142 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	8.9% 4/45 • Number of events 4 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	10.2% 5/49 • Number of events 5 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.3% 1/43 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.70% 1/142 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	6.7% 3/45 • Number of events 3 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	10.2% 5/49 • Number of events 5 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.3% 1/43 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Renal and urinary disorders Renal failure	0.00% 0/142 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.2% 1/45 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.0% 1/49 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	4.7% 2/43 • Number of events 2 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Gastrointestinal disorders Diarrhea	0.70% 1/142 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.2% 1/45 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	8.2% 4/49 • Number of events 4 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.3% 1/43 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Gastrointestinal disorders Mucositis	0.70% 1/142 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/45 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.0% 1/49 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/43 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Gastrointestinal disorders Gastrointestinal bleeding	0.70% 1/142 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/45 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/49 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/43 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
General disorders Fever	0.70% 1/142 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	11.1% 5/45 • Number of events 5 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	6.1% 3/49 • Number of events 3 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.3% 1/43 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
General disorders Asthenia	1.4% 2/142 • Number of events 2 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.2% 1/45 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	4.1% 2/49 • Number of events 2 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.3% 1/43 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Psychiatric disorders Confusional syndrome	0.70% 1/142 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/45 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/49 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/43 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Respiratory, thoracic and mediastinal disorders Pneumoniae	0.00% 0/142 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	4.4% 2/45 • Number of events 2 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	16.3% 8/49 • Number of events 8 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.3% 1/43 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Blood and lymphatic system disorders Anemia	0.00% 0/142 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	6.7% 3/45 • Number of events 3 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.0% 1/49 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/43 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.
Infections and infestations Sepsis	0.00% 0/142 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	2.2% 1/45 • Number of events 1 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	6.1% 3/49 • Number of events 3 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.	0.00% 0/43 • 60 Months The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial. Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial. During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication. The only SUSAR was: Severe afebrile neutropenia and renal failure.