Pemetrexed/Bevacizumab Maintenance Combo Stalls Lung Cancer

STOCKHOLM – Adding pemetrexed to bevacizumab maintenance therapy cut the relative risk of disease progression for patients with advanced nonsquamous non–small cell lung cancer in a phase III clinical trial.

Patients on the combination had a median progression-free survival of 10.2 months from the start of first-line induction therapy vs. 6.6 months with solo bevacizumab maintenance in the randomized open label study (hazard ratio, 0.50; P less than.001).

The same measure from randomization to maintenance therapy was twice as long with the combination therapy as with bevacizumab alone – 7.4 months vs. 3.7 months (HR = 0.48; P less than.001).

"First-line cisplatin/pemetrexed/bevacizumab followed by continuation maintenance with bevacizumab and pemetrexed achieved a patient PFS [progression-free survival] benefit of unprecedented magnitude," said Dr. Fabrice Barlesi, who presented the results of the AVAPERL trial at the European Multidisciplinary Cancer Congress.

The researchers recruited patients with previously untreated stage IIIB-IV advanced nonsquamous non–small cell lung cancer (nsNSCLC). All patients received four 3-week cycles of first-line induction with bevacizumab, pemetrexed (Alimta), and cisplatin.

Patients with complete response, partial response, or stable disease at the end of this treatment were randomized to continuation maintenance with bevacizumab or bevacizumab and pemetrexed in 3-week cycles until disease progression. Progression-free survival was assessed from the beginning of induction therapy to first progressive disease or death from any cause.

A total of 376 patients started first-line induction therapy; 123 were not eligible for randomization due to disease progression. Of the remainder, 253 patients were randomized to maintenance therapy with bevacizumab alone (125) or bevacizumab plus pemetrexed (128). Three patients did not receive maintenance treatment.

Median follow-up was 11 months for this analysis presented at the joint congress of the European Cancer Organization (ECCO), the European Society for Medical Oncology (ESMO), and the European Society for Radiotherapy and Oncology (ESTRO).

Overall survival from induction was 15.7 months with bevacizumab alone but has not been reached yet with the combination maintenance therapy, according to Dr. Barlesi of the multidisciplinary oncology and therapeutic innovations department at the Assistance Publique Hôpitaux de Marseille, France.

First-line therapy with cisplatin, pemetrexed, and bevacizumab was well tolerated with no new or unexpected toxicities.

Notably, grade 3-5 hematologic adverse events were greater with the bevacizumab plus pemetrexed arm vs. the control group (10% vs. 0%). Grade 3-5 nonhematologic events also were greater with the combination maintenance treatment (31% vs. 22%).

Pemetrexed is approved in the United States for maintenance treatment of nonsquamous locally advanced or metastatic non–small cell lung cancer that has not progressed after four cycles of platinum-based chemotherapy. AVAPERL was the first phase III trial to investigate the combination of pemetrexed and bevacizumab as maintenance therapy in this disease.

The study was funded by Hoffman-La Roche. Dr. Barlesi reported that he has been a consultant for and received research funding from Roche and Lilly. One of the study authors is an employee for Hoffman-La Roche.

STOCKHOLM – Adding pemetrexed to bevacizumab maintenance therapy cut the relative risk of disease progression for patients with advanced nonsquamous non–small cell lung cancer in a phase III clinical trial.

Patients on the combination had a median progression-free survival of 10.2 months from the start of first-line induction therapy vs. 6.6 months with solo bevacizumab maintenance in the randomized open label study (hazard ratio, 0.50; P less than.001).

The same measure from randomization to maintenance therapy was twice as long with the combination therapy as with bevacizumab alone – 7.4 months vs. 3.7 months (HR = 0.48; P less than.001).

"First-line cisplatin/pemetrexed/bevacizumab followed by continuation maintenance with bevacizumab and pemetrexed achieved a patient PFS [progression-free survival] benefit of unprecedented magnitude," said Dr. Fabrice Barlesi, who presented the results of the AVAPERL trial at the European Multidisciplinary Cancer Congress.

The researchers recruited patients with previously untreated stage IIIB-IV advanced nonsquamous non–small cell lung cancer (nsNSCLC). All patients received four 3-week cycles of first-line induction with bevacizumab, pemetrexed (Alimta), and cisplatin.

Patients with complete response, partial response, or stable disease at the end of this treatment were randomized to continuation maintenance with bevacizumab or bevacizumab and pemetrexed in 3-week cycles until disease progression. Progression-free survival was assessed from the beginning of induction therapy to first progressive disease or death from any cause.

A total of 376 patients started first-line induction therapy; 123 were not eligible for randomization due to disease progression. Of the remainder, 253 patients were randomized to maintenance therapy with bevacizumab alone (125) or bevacizumab plus pemetrexed (128). Three patients did not receive maintenance treatment.

Median follow-up was 11 months for this analysis presented at the joint congress of the European Cancer Organization (ECCO), the European Society for Medical Oncology (ESMO), and the European Society for Radiotherapy and Oncology (ESTRO).

Overall survival from induction was 15.7 months with bevacizumab alone but has not been reached yet with the combination maintenance therapy, according to Dr. Barlesi of the multidisciplinary oncology and therapeutic innovations department at the Assistance Publique Hôpitaux de Marseille, France.

First-line therapy with cisplatin, pemetrexed, and bevacizumab was well tolerated with no new or unexpected toxicities.

Notably, grade 3-5 hematologic adverse events were greater with the bevacizumab plus pemetrexed arm vs. the control group (10% vs. 0%). Grade 3-5 nonhematologic events also were greater with the combination maintenance treatment (31% vs. 22%).

Pemetrexed is approved in the United States for maintenance treatment of nonsquamous locally advanced or metastatic non–small cell lung cancer that has not progressed after four cycles of platinum-based chemotherapy. AVAPERL was the first phase III trial to investigate the combination of pemetrexed and bevacizumab as maintenance therapy in this disease.

The study was funded by Hoffman-La Roche. Dr. Barlesi reported that he has been a consultant for and received research funding from Roche and Lilly. One of the study authors is an employee for Hoffman-La Roche.

STOCKHOLM – Adding pemetrexed to bevacizumab maintenance therapy cut the relative risk of disease progression for patients with advanced nonsquamous non–small cell lung cancer in a phase III clinical trial.

Patients on the combination had a median progression-free survival of 10.2 months from the start of first-line induction therapy vs. 6.6 months with solo bevacizumab maintenance in the randomized open label study (hazard ratio, 0.50; P less than.001).

The same measure from randomization to maintenance therapy was twice as long with the combination therapy as with bevacizumab alone – 7.4 months vs. 3.7 months (HR = 0.48; P less than.001).

"First-line cisplatin/pemetrexed/bevacizumab followed by continuation maintenance with bevacizumab and pemetrexed achieved a patient PFS [progression-free survival] benefit of unprecedented magnitude," said Dr. Fabrice Barlesi, who presented the results of the AVAPERL trial at the European Multidisciplinary Cancer Congress.

The researchers recruited patients with previously untreated stage IIIB-IV advanced nonsquamous non–small cell lung cancer (nsNSCLC). All patients received four 3-week cycles of first-line induction with bevacizumab, pemetrexed (Alimta), and cisplatin.

Patients with complete response, partial response, or stable disease at the end of this treatment were randomized to continuation maintenance with bevacizumab or bevacizumab and pemetrexed in 3-week cycles until disease progression. Progression-free survival was assessed from the beginning of induction therapy to first progressive disease or death from any cause.

A total of 376 patients started first-line induction therapy; 123 were not eligible for randomization due to disease progression. Of the remainder, 253 patients were randomized to maintenance therapy with bevacizumab alone (125) or bevacizumab plus pemetrexed (128). Three patients did not receive maintenance treatment.

Median follow-up was 11 months for this analysis presented at the joint congress of the European Cancer Organization (ECCO), the European Society for Medical Oncology (ESMO), and the European Society for Radiotherapy and Oncology (ESTRO).

Overall survival from induction was 15.7 months with bevacizumab alone but has not been reached yet with the combination maintenance therapy, according to Dr. Barlesi of the multidisciplinary oncology and therapeutic innovations department at the Assistance Publique Hôpitaux de Marseille, France.

First-line therapy with cisplatin, pemetrexed, and bevacizumab was well tolerated with no new or unexpected toxicities.

Notably, grade 3-5 hematologic adverse events were greater with the bevacizumab plus pemetrexed arm vs. the control group (10% vs. 0%). Grade 3-5 nonhematologic events also were greater with the combination maintenance treatment (31% vs. 22%).

Pemetrexed is approved in the United States for maintenance treatment of nonsquamous locally advanced or metastatic non–small cell lung cancer that has not progressed after four cycles of platinum-based chemotherapy. AVAPERL was the first phase III trial to investigate the combination of pemetrexed and bevacizumab as maintenance therapy in this disease.

The study was funded by Hoffman-La Roche. Dr. Barlesi reported that he has been a consultant for and received research funding from Roche and Lilly. One of the study authors is an employee for Hoffman-La Roche.