Pazopanib

Pazopanib was evaluated in a randomized, placebo-controlled, international trial (VEG015192 [NCT00334282]) that enrolled 435 patients with clear cell or predominantly clear cell renal cell carcinoma.[28] Nearly 50% of the patients had previously received cytokine therapy, although the remainder of them were treatment naïve.

Pazopanib was evaluated in a randomized, placebo-controlled, international trial (VEG015192 [NCT00334282]) that enrolled 435 patients with clear cell or predominantly clear cell renal cell carcinoma.[28] Nearly 50% of the patients had previously received cytokine therapy, although the remainder of them were treatment naïve.

PFS was significantly prolonged in the pazopanib arm at 9.2 months compared with 4.2 months in the placebo arm.

Pazopanib was evaluated in a randomized, placebo-controlled, international trial (VEG015192 [NCT00334282]) that enrolled 435 patients with clear cell or predominantly clear cell renal cell carcinoma.[28] Nearly 50% of the patients had previously received cytokine therapy, although the remainder of them were treatment naïve.

The HR for progression was 0.46 (95% CI, 0.34–0.62; P < .0001), and the median duration of response was longer than 1 year.

Pazopanib was also compared with sunitinib in a randomized controlled trial (NCT00720941) that enrolled 1,110 patients who had metastatic renal cell carcinoma with a clear cell component in a 1:1 ratio.[14] The primary end point was PFS. The study was powered to assess the noninferiority of pazopanib. Results were reported when there was disease progression in 336 of 557 patients (60%) who received pazopanib and in 323 of 553 patients (58%) who received sunitinib.

Pazopanib was also compared with sunitinib in a randomized controlled trial (NCT00720941) that enrolled 1,110 patients who had metastatic renal cell carcinoma with a clear cell component in a 1:1 ratio.[14] The primary end point was PFS. The study was powered to assess the noninferiority of pazopanib. Results were reported when there was disease progression in 336 of 557 patients (60%) who received pazopanib and in 323 of 553 patients (58%) who received sunitinib.

The median PFS was 8.4 months for those in the pazopanib arm and 9.5 months for those in the sunitinib arm (HR, 1.05; CI, 0.9–1.22).

Pazopanib was also compared with sunitinib in a randomized controlled trial (NCT00720941) that enrolled 1,110 patients who had metastatic renal cell carcinoma with a clear cell component in a 1:1 ratio.[14] The primary end point was PFS. The study was powered to assess the noninferiority of pazopanib. Results were reported when there was disease progression in 336 of 557 patients (60%) who received pazopanib and in 323 of 553 patients (58%) who received sunitinib.

There was no difference in OS (HR, 0.91; 95% CI, 0.76–1.08).

Pazopanib was also compared with sunitinib in a randomized controlled trial (NCT00720941) that enrolled 1,110 patients who had metastatic renal cell carcinoma with a clear cell component in a 1:1 ratio.[14] The primary end point was PFS. The study was powered to assess the noninferiority of pazopanib. Results were reported when there was disease progression in 336 of 557 patients (60%) who received pazopanib and in 323 of 553 patients (58%) who received sunitinib.

Although QOL was compared in the study, differences in the scheduled administration of the medications made this comparison difficult to interpret.

A subsequent double-blind, randomized, controlled, crossover trial compared sunitinib followed by pazopanib with pazopanib followed by sunitinib. The primary end point was patient preference for one drug over the other.[15] Patients were treated for 10 weeks with either sunitinib or pazopanib, followed by a 2-week washout period, followed by 10 more weeks of treatment with the other drug. Preference was assessed at the end of the second 10-week treatment period. This study design created possible bias in favor of pazopanib.Although the typical regimen for administering sunitinib is a 6-week cycle of 4 weeks on the drug and 2 weeks off the drug, the Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer (PISCES [NCT01064310]) chose a treatment period of 10 weeks rather than 12 weeks. Because of this treatment-period change, the 10 weeks of sunitinib treatment included 4 weeks on the drug, followed by 2 weeks off the drug, followed by 4 more weeks on the drug. Patients assigned to pazopanib followed by sunitinib had their preference for treatment assessed at the end of the second 4-weeks-on-the-drug period during which they took sunitinib daily for 28 days. At that point, the sunitinib side effects became the most severe. The expected result from an assessment conducted at the end of a 6-week treatment cycle versus the 4-week treatment cycle would be greatly abated side effects.In addition, the 2-week washout period that occurred between the two 10-week treatment periods was a true break from treatment for patients assigned to take pazopanib first; however, for the patients taking sunitinib, the 2-week washout period was just the completion of their second 6-week treatment cycle. In other words, patients assigned to pazopanib first had a true 2-week break from treatment, and their drug preference was assessed at the peak period of toxic effects from sunitinib; however, the patients assigned to sunitinib first had no true treatment break before starting pazopanib and may have had less opportunity to recover from the side effects of sunitinib.

A subsequent double-blind, randomized, controlled, crossover trial compared sunitinib followed by pazopanib with pazopanib followed by sunitinib. The primary end point was patient preference for one drug over the other.[15] Patients were treated for 10 weeks with either sunitinib or pazopanib, followed by a 2-week washout period, followed by 10 more weeks of treatment with the other drug. Preference was assessed at the end of the second 10-week treatment period. This study design created possible bias in favor of pazopanib.Although the typical regimen for administering sunitinib is a 6-week cycle of 4 weeks on the drug and 2 weeks off the drug, the Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer (PISCES [NCT01064310]) chose a treatment period of 10 weeks rather than 12 weeks. Because of this treatment-period change, the 10 weeks of sunitinib treatment included 4 weeks on the drug, followed by 2 weeks off the drug, followed by 4 more weeks on the drug. Patients assigned to pazopanib followed by sunitinib had their preference for treatment assessed at the end of the second 4-weeks-on-the-drug period during which they took sunitinib daily for 28 days. At that point, the sunitinib side effects became the most severe. The expected result from an assessment conducted at the end of a 6-week treatment cycle versus the 4-week treatment cycle would be greatly abated side effects.In addition, the 2-week washout period that occurred between the two 10-week treatment periods was a true break from treatment for patients assigned to take pazopanib first; however, for the patients taking sunitinib, the 2-week washout period was just the completion of their second 6-week treatment cycle. In other words, patients assigned to pazopanib first had a true 2-week break from treatment, and their drug preference was assessed at the peak period of toxic effects from sunitinib; however, the patients assigned to sunitinib first had no true treatment break before starting pazopanib and may have had less opportunity to recover from the side effects of sunitinib.

Despite these limitations, 70% of the patients preferred pazopanib, and 22% of the patients preferred sunitinib (P < .001).

A subsequent double-blind, randomized, controlled, crossover trial compared sunitinib followed by pazopanib with pazopanib followed by sunitinib. The primary end point was patient preference for one drug over the other.[15] Patients were treated for 10 weeks with either sunitinib or pazopanib, followed by a 2-week washout period, followed by 10 more weeks of treatment with the other drug. Preference was assessed at the end of the second 10-week treatment period. This study design created possible bias in favor of pazopanib.Although the typical regimen for administering sunitinib is a 6-week cycle of 4 weeks on the drug and 2 weeks off the drug, the Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer (PISCES [NCT01064310]) chose a treatment period of 10 weeks rather than 12 weeks. Because of this treatment-period change, the 10 weeks of sunitinib treatment included 4 weeks on the drug, followed by 2 weeks off the drug, followed by 4 more weeks on the drug. Patients assigned to pazopanib followed by sunitinib had their preference for treatment assessed at the end of the second 4-weeks-on-the-drug period during which they took sunitinib daily for 28 days. At that point, the sunitinib side effects became the most severe. The expected result from an assessment conducted at the end of a 6-week treatment cycle versus the 4-week treatment cycle would be greatly abated side effects.In addition, the 2-week washout period that occurred between the two 10-week treatment periods was a true break from treatment for patients assigned to take pazopanib first; however, for the patients taking sunitinib, the 2-week washout period was just the completion of their second 6-week treatment cycle. In other words, patients assigned to pazopanib first had a true 2-week break from treatment, and their drug preference was assessed at the peak period of toxic effects from sunitinib; however, the patients assigned to sunitinib first had no true treatment break before starting pazopanib and may have had less opportunity to recover from the side effects of sunitinib.

More patients preferred pazopanib regardless of the treatment they received first; however, that difference was greater for the patients who received pazopanib first (80% vs. 11%) compared with the patients who received sunitinib first (62% vs. 32%).

A subsequent double-blind, randomized, controlled, crossover trial compared sunitinib followed by pazopanib with pazopanib followed by sunitinib. The primary end point was patient preference for one drug over the other.[15] Patients were treated for 10 weeks with either sunitinib or pazopanib, followed by a 2-week washout period, followed by 10 more weeks of treatment with the other drug. Preference was assessed at the end of the second 10-week treatment period. This study design created possible bias in favor of pazopanib.Although the typical regimen for administering sunitinib is a 6-week cycle of 4 weeks on the drug and 2 weeks off the drug, the Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer (PISCES [NCT01064310]) chose a treatment period of 10 weeks rather than 12 weeks. Because of this treatment-period change, the 10 weeks of sunitinib treatment included 4 weeks on the drug, followed by 2 weeks off the drug, followed by 4 more weeks on the drug. Patients assigned to pazopanib followed by sunitinib had their preference for treatment assessed at the end of the second 4-weeks-on-the-drug period during which they took sunitinib daily for 28 days. At that point, the sunitinib side effects became the most severe. The expected result from an assessment conducted at the end of a 6-week treatment cycle versus the 4-week treatment cycle would be greatly abated side effects.In addition, the 2-week washout period that occurred between the two 10-week treatment periods was a true break from treatment for patients assigned to take pazopanib first; however, for the patients taking sunitinib, the 2-week washout period was just the completion of their second 6-week treatment cycle. In other words, patients assigned to pazopanib first had a true 2-week break from treatment, and their drug preference was assessed at the peak period of toxic effects from sunitinib; however, the patients assigned to sunitinib first had no true treatment break before starting pazopanib and may have had less opportunity to recover from the side effects of sunitinib.

The main side effects cited by the patients that contributed to patient preference were diarrhea, HRQOL, fatigue, loss of appetite, taste changes, nausea and vomiting, hand and foot soreness, stomach pain, and mouth and throat soreness.

A subsequent double-blind, randomized, controlled, crossover trial compared sunitinib followed by pazopanib with pazopanib followed by sunitinib. The primary end point was patient preference for one drug over the other.[15] Patients were treated for 10 weeks with either sunitinib or pazopanib, followed by a 2-week washout period, followed by 10 more weeks of treatment with the other drug. Preference was assessed at the end of the second 10-week treatment period. This study design created possible bias in favor of pazopanib.Although the typical regimen for administering sunitinib is a 6-week cycle of 4 weeks on the drug and 2 weeks off the drug, the Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer (PISCES [NCT01064310]) chose a treatment period of 10 weeks rather than 12 weeks. Because of this treatment-period change, the 10 weeks of sunitinib treatment included 4 weeks on the drug, followed by 2 weeks off the drug, followed by 4 more weeks on the drug. Patients assigned to pazopanib followed by sunitinib had their preference for treatment assessed at the end of the second 4-weeks-on-the-drug period during which they took sunitinib daily for 28 days. At that point, the sunitinib side effects became the most severe. The expected result from an assessment conducted at the end of a 6-week treatment cycle versus the 4-week treatment cycle would be greatly abated side effects.In addition, the 2-week washout period that occurred between the two 10-week treatment periods was a true break from treatment for patients assigned to take pazopanib first; however, for the patients taking sunitinib, the 2-week washout period was just the completion of their second 6-week treatment cycle. In other words, patients assigned to pazopanib first had a true 2-week break from treatment, and their drug preference was assessed at the peak period of toxic effects from sunitinib; however, the patients assigned to sunitinib first had no true treatment break before starting pazopanib and may have had less opportunity to recover from the side effects of sunitinib.

The patients who preferred pazopanib cited less fatigue and better overall QOL as the most common reasons for their preference.

A subsequent double-blind, randomized, controlled, crossover trial compared sunitinib followed by pazopanib with pazopanib followed by sunitinib. The primary end point was patient preference for one drug over the other.[15] Patients were treated for 10 weeks with either sunitinib or pazopanib, followed by a 2-week washout period, followed by 10 more weeks of treatment with the other drug. Preference was assessed at the end of the second 10-week treatment period. This study design created possible bias in favor of pazopanib.Although the typical regimen for administering sunitinib is a 6-week cycle of 4 weeks on the drug and 2 weeks off the drug, the Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer (PISCES [NCT01064310]) chose a treatment period of 10 weeks rather than 12 weeks. Because of this treatment-period change, the 10 weeks of sunitinib treatment included 4 weeks on the drug, followed by 2 weeks off the drug, followed by 4 more weeks on the drug. Patients assigned to pazopanib followed by sunitinib had their preference for treatment assessed at the end of the second 4-weeks-on-the-drug period during which they took sunitinib daily for 28 days. At that point, the sunitinib side effects became the most severe. The expected result from an assessment conducted at the end of a 6-week treatment cycle versus the 4-week treatment cycle would be greatly abated side effects.In addition, the 2-week washout period that occurred between the two 10-week treatment periods was a true break from treatment for patients assigned to take pazopanib first; however, for the patients taking sunitinib, the 2-week washout period was just the completion of their second 6-week treatment cycle. In other words, patients assigned to pazopanib first had a true 2-week break from treatment, and their drug preference was assessed at the peak period of toxic effects from sunitinib; however, the patients assigned to sunitinib first had no true treatment break before starting pazopanib and may have had less opportunity to recover from the side effects of sunitinib.

The patients who preferred sunitinib cited less diarrhea and better QOL as the most common reasons for their preference.

A subsequent double-blind, randomized, controlled, crossover trial compared sunitinib followed by pazopanib with pazopanib followed by sunitinib. The primary end point was patient preference for one drug over the other.[15] Patients were treated for 10 weeks with either sunitinib or pazopanib, followed by a 2-week washout period, followed by 10 more weeks of treatment with the other drug. Preference was assessed at the end of the second 10-week treatment period. This study design created possible bias in favor of pazopanib.Although the typical regimen for administering sunitinib is a 6-week cycle of 4 weeks on the drug and 2 weeks off the drug, the Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer (PISCES [NCT01064310]) chose a treatment period of 10 weeks rather than 12 weeks. Because of this treatment-period change, the 10 weeks of sunitinib treatment included 4 weeks on the drug, followed by 2 weeks off the drug, followed by 4 more weeks on the drug. Patients assigned to pazopanib followed by sunitinib had their preference for treatment assessed at the end of the second 4-weeks-on-the-drug period during which they took sunitinib daily for 28 days. At that point, the sunitinib side effects became the most severe. The expected result from an assessment conducted at the end of a 6-week treatment cycle versus the 4-week treatment cycle would be greatly abated side effects.In addition, the 2-week washout period that occurred between the two 10-week treatment periods was a true break from treatment for patients assigned to take pazopanib first; however, for the patients taking sunitinib, the 2-week washout period was just the completion of their second 6-week treatment cycle. In other words, patients assigned to pazopanib first had a true 2-week break from treatment, and their drug preference was assessed at the peak period of toxic effects from sunitinib; however, the patients assigned to sunitinib first had no true treatment break before starting pazopanib and may have had less opportunity to recover from the side effects of sunitinib.

Physician preference was a secondary end point of the study, and 61% of physicians preferred to continue patient treatment with pazopanib, compared with 22% of physicians who preferred to continue patient treatment with sunitinib.