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2009 ASCO Annual Meeting
News
Special Report: Conference 2009 ASCO Annual Meeting Susumu Nishinaga/Science Photo Library
Timing of treatment?
The 44th annual meeting of the American Society of Clinical Oncology was held on May 29–June 2, 2009, in Orlando, FL, USA
Gordon Rustin (Northwood, UK) and colleagues presented findings of the MRC OV05/EORTC 55955 randomised trial, which aimed to assess whether treatment for relapsed ovarian cancer should begin as soon as blood tests show increases in the concentration of CA125, or whether it should be delayed until clinically indicated. Of the 1442 women who were enrolled when in complete remission after treatment with first-line platinum-containing regimens, 527 subsequently relapsed. Of these patients, 264 were randomly assigned to the immediate treatment group and 263 to the delayed treatment group. After a median followup of 49 months, during which time 351 of the women died, the researchers noted no difference in overall survival between the groups (hazard ratio [HR] 1·00 [95% CI 0·82–1·22]; p=0·98), suggesting that there is no need to assess CA125 routinely in women whose ovarian cancer is in remission.
PARP inhibitors Several phase II trials of poly-ADPribose-polymerase (PARP) inhibitors were reported at this year’s meeting. Joyce O’Shaughnessy (Dallas, TX, USA) and colleagues reported findings of a placebo-controlled trial of BSI-201 given in combination with gemcitabine and carboplatin to women with metastatic triple-negative breast cancer. Although the trial is ongoing, an interim analysis suggests that the drug is highly active in this setting, with a RECIST-defined objective response rate (ORR) of 48% in the BSI-201 group, compared with 16% in the control group (HR for progression-free survival [PFS] 0·34 [95% CI 0·20–0·58]; p<0·0001). No differences in the occurrence, severity, or type of adverse events were noted between groups. Two trials of a second PARP inhibitor, olaparib, were also reported, one in BRCA-deficient breast 650
cancer, and the other in BRCA-deficient ovarian cancer. The drug seemed active in both settings at the maximum tolerated dose of 400 mg twice daily, with an ORR of 33% (11 of 33 patients) in ovarian cancer and 38% (nine of 24) in breast cancer. Most adverse events were grade 1 or 2 in severity; the most common grade-3 events were nausea (five patients in the breast-cancer trial, four in the ovarian trial) and fatigue (three patients in the breast-cancer trial).
Elesclomol for melanoma Findings of a phase III trial of an oxidative-stress inducer, elesclomol, intended to increase mitochondrialinduced apoptosis in tumour cells, were presented by Axel Hauschild (Kiel, Germany) and colleagues. 651 patients with metastatic melanoma were randomly assigned to receive either paclitaxel plus elesclomol or to paclitaxel alone. The trial was stopped early because of an increased risk of death in the elesclomol group (80 deaths vs 53 in the control group); an analysis of PFS in the 411 eligible patients (219 events) showed no difference between the groups (HR 0·88 [95% CI 0·67–1·16]; p=0·37).
Pazopanib for renal cell cancer Cora Sternberg (Rome, Italy) and colleagues presented data from the VEG105192 study, a phase III trial of pazopanib, an oral multikinase inhibitor that targets angiogenesis pathways. 435 patients with renal-cell cancer who were either treatment-naive or who had received cytokines were randomly assigned in a 2:1 ratio to receive either pazopanib twice daily (290 patients) or to placebo (145 patients). PFS was 9·2 months in the pazopanib group, compared with 4·2 months in the placebo group (HR 0·46 [95% CI 0·34–0·62]; p<0·0001); the difference in survival was particularly pronounced
in the treatment-naive patients (11·1 vs 2·8 months; HR 0·40 [95% CI 0·27–0·60]; p<0·0001). Most adverse events were grade 1 or 2, the most commonly reported with pazopanib being diarrhoea (52%; 4% grade 3/4), hypertension (40%; 4% grade 3/4), and change in hair colour (38%; <1% grade 3/4).
Oxaliplatin and neurotoxicity Axel Grothey (Rochester, MD, USA) and colleagues assessed in a phase III trial whether the administration of intravenous calcium and magnesium could alleviate acute and chronic oxaliplatinrelated neurotoxicity. 104 patients with colorectal cancer receiving an adjuvant fluorouracil, leucovorin, and oxaliplatin regimen were randomly assigned to receive either intravenous calcium and magnesium or to placebo. The ions had little effect on acute neurotoxicity, but significantly reduced the severity of a number of the cumulative, chronic effects of oxaliplatin.
Amrubicin in lung cancers Amrubicin—an inhibitor of topoisomerase II—is approved for use in patients with lung cancer in Japan. A phase II trial in western populations was presented by David Ettinger (Baltimore, MD, USA) and colleagues, who tested the drug as monotherapy in 69 patients with treatmentrefractory small-cell lung cancer. An ORR of 21% (one complete response, 15 partial responses) was noted, with the most common grade 3 or 4 adverse events being neutropenia (65%), thrombocytopenia (39%), and leucopenia (35%). Promising results were also noted in trials from Japan in patients with small-cell or non-small cell-lung cancer, both as monotherapy and in combination with other chemotherapeutic drugs.
Rob Brierley www.thelancet.com/oncology Vol 10 July 2009
Special Report: Conference 2009 ASCO Annual Meeting Susumu Nishinaga/Science Photo Library
Timing of treatment?
The 44th annual meeting of the American Society of Clinical Oncology was held on May 29–June 2, 2009, in Orlando, FL, USA
Gordon Rustin (Northwood, UK) and colleagues presented findings of the MRC OV05/EORTC 55955 randomised trial, which aimed to assess whether treatment for relapsed ovarian cancer should begin as soon as blood tests show increases in the concentration of CA125, or whether it should be delayed until clinically indicated. Of the 1442 women who were enrolled when in complete remission after treatment with first-line platinum-containing regimens, 527 subsequently relapsed. Of these patients, 264 were randomly assigned to the immediate treatment group and 263 to the delayed treatment group. After a median followup of 49 months, during which time 351 of the women died, the researchers noted no difference in overall survival between the groups (hazard ratio [HR] 1·00 [95% CI 0·82–1·22]; p=0·98), suggesting that there is no need to assess CA125 routinely in women whose ovarian cancer is in remission.
PARP inhibitors Several phase II trials of poly-ADPribose-polymerase (PARP) inhibitors were reported at this year’s meeting. Joyce O’Shaughnessy (Dallas, TX, USA) and colleagues reported findings of a placebo-controlled trial of BSI-201 given in combination with gemcitabine and carboplatin to women with metastatic triple-negative breast cancer. Although the trial is ongoing, an interim analysis suggests that the drug is highly active in this setting, with a RECIST-defined objective response rate (ORR) of 48% in the BSI-201 group, compared with 16% in the control group (HR for progression-free survival [PFS] 0·34 [95% CI 0·20–0·58]; p<0·0001). No differences in the occurrence, severity, or type of adverse events were noted between groups. Two trials of a second PARP inhibitor, olaparib, were also reported, one in BRCA-deficient breast 650
cancer, and the other in BRCA-deficient ovarian cancer. The drug seemed active in both settings at the maximum tolerated dose of 400 mg twice daily, with an ORR of 33% (11 of 33 patients) in ovarian cancer and 38% (nine of 24) in breast cancer. Most adverse events were grade 1 or 2 in severity; the most common grade-3 events were nausea (five patients in the breast-cancer trial, four in the ovarian trial) and fatigue (three patients in the breast-cancer trial).
Elesclomol for melanoma Findings of a phase III trial of an oxidative-stress inducer, elesclomol, intended to increase mitochondrialinduced apoptosis in tumour cells, were presented by Axel Hauschild (Kiel, Germany) and colleagues. 651 patients with metastatic melanoma were randomly assigned to receive either paclitaxel plus elesclomol or to paclitaxel alone. The trial was stopped early because of an increased risk of death in the elesclomol group (80 deaths vs 53 in the control group); an analysis of PFS in the 411 eligible patients (219 events) showed no difference between the groups (HR 0·88 [95% CI 0·67–1·16]; p=0·37).
Pazopanib for renal cell cancer Cora Sternberg (Rome, Italy) and colleagues presented data from the VEG105192 study, a phase III trial of pazopanib, an oral multikinase inhibitor that targets angiogenesis pathways. 435 patients with renal-cell cancer who were either treatment-naive or who had received cytokines were randomly assigned in a 2:1 ratio to receive either pazopanib twice daily (290 patients) or to placebo (145 patients). PFS was 9·2 months in the pazopanib group, compared with 4·2 months in the placebo group (HR 0·46 [95% CI 0·34–0·62]; p<0·0001); the difference in survival was particularly pronounced
in the treatment-naive patients (11·1 vs 2·8 months; HR 0·40 [95% CI 0·27–0·60]; p<0·0001). Most adverse events were grade 1 or 2, the most commonly reported with pazopanib being diarrhoea (52%; 4% grade 3/4), hypertension (40%; 4% grade 3/4), and change in hair colour (38%; <1% grade 3/4).
Oxaliplatin and neurotoxicity Axel Grothey (Rochester, MD, USA) and colleagues assessed in a phase III trial whether the administration of intravenous calcium and magnesium could alleviate acute and chronic oxaliplatinrelated neurotoxicity. 104 patients with colorectal cancer receiving an adjuvant fluorouracil, leucovorin, and oxaliplatin regimen were randomly assigned to receive either intravenous calcium and magnesium or to placebo. The ions had little effect on acute neurotoxicity, but significantly reduced the severity of a number of the cumulative, chronic effects of oxaliplatin.
Amrubicin in lung cancers Amrubicin—an inhibitor of topoisomerase II—is approved for use in patients with lung cancer in Japan. A phase II trial in western populations was presented by David Ettinger (Baltimore, MD, USA) and colleagues, who tested the drug as monotherapy in 69 patients with treatmentrefractory small-cell lung cancer. An ORR of 21% (one complete response, 15 partial responses) was noted, with the most common grade 3 or 4 adverse events being neutropenia (65%), thrombocytopenia (39%), and leucopenia (35%). Promising results were also noted in trials from Japan in patients with small-cell or non-small cell-lung cancer, both as monotherapy and in combination with other chemotherapeutic drugs.
Rob Brierley www.thelancet.com/oncology Vol 10 July 2009