NCT04682587

To Examine the Effects of Axitinib Dose Reduction and Interruption for Adverse Event Management Among Patients Receiving Axitinib in for the Treatment of Advanced Renal Cell Carcinoma

Completed Results posted Last updated 3 January 2025

What this trial tests

trial testing Axitinib in Renal Cell Carcinoma in 481 participants. Completed in 5 April 2021.

Timeline

24 February 2021

Primary endpoint
5 April 2021

5 April 2021

Quick facts

Lead sponsor	Pfizer
Status	Completed
Study type	OBSERVATIONAL
Enrollment	481
Start date	24 February 2021
Primary completion	5 April 2021
Estimated completion	5 April 2021
Sites	1 location across United States

Drugs / interventions tested

• Axitinib — full drug profile →
• Avelumab (avelumab) — full drug profile →
• Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Renal Cell Carcinoma — all drugs for Renal Cell Carcinoma →

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Renal Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Different Type of Adverse Events Primary · Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months

An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data

Fatigue

Group	Value	95% CI
Axitinib + IOs	232

Diarrhea

Group	Value	95% CI
Axitinib + IOs	184

Nausea

Group	Value	95% CI
Axitinib + IOs	141

Hypertension

Group	Value	95% CI
Axitinib + IOs	106

Palmar-plantar erythrodysesthesia

Group	Value	95% CI
Axitinib + IOs	54

Number of Participants With Serious Adverse Events Primary · 6 months

AE was considered serious when it: resulted in death, life-threatening, requires in-participant hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may jeopardize the participant or may require intervention to prevent one of the outcomes listed above. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for fir

Group	Value	95% CI
Axitinib + IOs	130

Duration From Treatment Initiation to Onset of Adverse Events Primary · Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months

An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. In this outcome measure time from index date to occurrence of incidence of any AE is reported. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up,

Group	Value	95% CI
Axitinib + IOs	1.0	0.3 – 2.0

Duration of Adverse Events From Onset to Resolution Primary · Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months

The time to resolution from AE onset and from initiation of management strategy was calculated for all AEs experienced including repeated AEs. The time to resolution of AE (from the onset of AE and from the initiation of management strategies) was separately estimated using Kaplan-Meier analysis; median time to event will be reported. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from

Overall

Group	Value	95% CI
Axitinib + IOs	21.0	9.0 – 33.0

Severe AE's

Group	Value	95% CI
Axitinib + IOs	17.0	6.0 – 31.0

Number of Adverse Events Classified According to Type of Management Strategy Primary · Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the

No Action

Group	Value	95% CI
Axitinib + IOs	198

Axitinib modifications (with or without supportive care)

Group	Value	95% CI
Axitinib + IOs	251

Axitinib modifications with IO treatment modification

Group	Value	95% CI
Axitinib + IOs	96

Duration of Treatment Interruption for Axitinib Primary · Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 month

Duration of treatment interruption was calculated as the total days of treatment interruption. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants.

Group	Value	95% CI
Axitinib + IOs	13.0	7.0 – 21.0

Maximum Axitinib Dose Reduction Primary · Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months

Maximum axitinib dose reduction was calculated as the difference between axitinib dose at AE onset and the minimum axitinib dose recorded between the date of AE onset and either the date of AE resolution (if the AE had a reported resolution date) or the end of follow up (if the AE did not have a reported resolution date).Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to

Group	Value	95% CI
Axitinib + IOs	3.0	2.0 – 3.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Axitinib + IOs

Serious: 130/481 (27%)

Deaths: 32/481

Serious adverse events (5 terms)

Reaction	System	Axitinib + IOs
Diarrhoea	Gastrointestinal disorders	—
Hypertension	Vascular disorders	—
Fatigue	General disorders	—
Nausea	Gastrointestinal disorders	—
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	—

Other adverse events (5 terms — click to expand)

Reaction	System	Axitinib + IOs
Fatigue	General disorders	—
Diarrhoea	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Hypertension	Vascular disorders	—
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	—

Most-reported serious reactions: Diarrhoea, Hypertension, Fatigue, Nausea, Palmar-plantar erythrodysaesthesia syndrome.

Data from ClinicalTrials.gov NCT04682587 adverse events section.

Sponsor's own description

To assess how dose reductions or treatment interruptions related to axitinib can be implemented to manage and resolve adverse events occurring among patients with advanced renal cell carcinoma treated with first-line axitinib in combination with avelumab or pembrolizumab

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cabozantinib in combination with immune checkpoint inhibitors for renal cell carcinoma: a systematic review and meta-analysis.
   Su J, Zhang J, Wu Y, Ni C, et al · · 2024 · cited 3× · PMID 38694912 · DOI 10.3389/fphar.2024.1322473
2. Impact of Therapy Management on Axitinib-Related Adverse Events in Patients With Advanced Renal Cell Carcinoma Receiving First-Line Axitinib + Checkpoint Inhibitor.
   Zakharia Y, Huynh L, Du S, Chang R, et al · · 2023 · cited 2× · PMID 37087399 · DOI 10.1016/j.clgc.2023.03.017