転移性大腸癌 奏功(腫瘍径の変化)と生命延長効果は関連しない
N9741試験とAVF2107試験の比較解析
転移性大腸癌に対する1st line化学療法を検討した2試験では・・
AVF2107試験: IFL+bevacizumab vs. FU/LV+bevacizumab vs. IFL+プラセボ
N9741試験: IFL vs. FOLFOX vs. IROX
IFL+bevacizumab vs. IFL 奏功例 非奏功例
増悪のHazard ratio 0.53(p=0.0002) 0.63(p=0.0188)
死亡のHazard ratio 0.60(p=0.0136) 0.76(p=0.0188)
FOLFOX vs. IFL 奏功例 非奏功例 SD例
PFS改善のHazard ratio 0.89(p=0.3166) 0.75(p=0.0029) 0.78(p=0.0795)
死亡のHazard ratio 0.71(p=0.0047) 0.74(p=0.0030)
IFLよりも有効性が示されているレジメンにより、
奏功例か否かの評価は生命予後の指標になっていないことが示された。
PURPOSE:
In the phase III study AVF2107g, bevacizumab (BV) demonstrated a
survival benefit when added to irinotecan, fluorouracil, and leucovorin (IFL) in first-line metastatic colorectal cancer (mCRC). In a parallel phase III study,Intergroup N9741, oxaliplatin plus fluorouracil and leucovorin (FOLFOX) also demonstrated a survival benefit compared with IFL. As these two superior therapies have differing mechanisms of action, we explored whether the improved survival associated with the superior therapy was dependent on tumor response.
PATIENTS AND METHODS:
For these retrospective, exploratory analyses, patients were defined as responders or nonresponders by whether complete or partialresponse was achieved with first-line therapy.
RESULTS:
Compared with IFL alone, BV plus IFL and FOLFOX each demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) regardless of objective tumor response. BV-treated nonresponders had a hazard ratio (HR) of 0.63 (P = .0001) for PFS and 0.76 (P = .0188) for OS compared with IFL-treated nonresponders. FOLFOX-treated nonresponders had an HR of 0.75 (P = .0029) for PFS and 0.74 (P = .0030) for OS compared with IFL-treated nonresponders.
CONCLUSION:
In both AVF2107g and N9741, objective response did not predict the magnitude of PFS or OS benefit from the superior therapy; nonresponders, despite a poorer prognosis than responders, achieved extended PFS and OS from BV plus IFL or FOLFOX compared with IFL. On the basis of these data, tumor response in metastatic colorectal cancer is not a necessary factor for a therapy to provide benefit to an individual patient.
Grothey A et al.
Response-independent survival benefit in metastatic colorectal cancer: a
comparative analysis of N9741 and AVF2107.
J Clin Oncol. 2008 Jan 10;26(2):183-9. PMID: 18182660
N9741試験とAVF2107試験の比較解析
転移性大腸癌に対する1st line化学療法を検討した2試験では・・
AVF2107試験: IFL+bevacizumab vs. FU/LV+bevacizumab vs. IFL+プラセボ
N9741試験: IFL vs. FOLFOX vs. IROX
IFL+bevacizumab vs. IFL 奏功例 非奏功例
増悪のHazard ratio 0.53(p=0.0002) 0.63(p=0.0188)
死亡のHazard ratio 0.60(p=0.0136) 0.76(p=0.0188)
FOLFOX vs. IFL 奏功例 非奏功例 SD例
PFS改善のHazard ratio 0.89(p=0.3166) 0.75(p=0.0029) 0.78(p=0.0795)
死亡のHazard ratio 0.71(p=0.0047) 0.74(p=0.0030)
IFLよりも有効性が示されているレジメンにより、
奏功例か否かの評価は生命予後の指標になっていないことが示された。
PURPOSE:
In the phase III study AVF2107g, bevacizumab (BV) demonstrated a
survival benefit when added to irinotecan, fluorouracil, and leucovorin (IFL) in first-line metastatic colorectal cancer (mCRC). In a parallel phase III study,Intergroup N9741, oxaliplatin plus fluorouracil and leucovorin (FOLFOX) also demonstrated a survival benefit compared with IFL. As these two superior therapies have differing mechanisms of action, we explored whether the improved survival associated with the superior therapy was dependent on tumor response.
PATIENTS AND METHODS:
For these retrospective, exploratory analyses, patients were defined as responders or nonresponders by whether complete or partialresponse was achieved with first-line therapy.
RESULTS:
Compared with IFL alone, BV plus IFL and FOLFOX each demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) regardless of objective tumor response. BV-treated nonresponders had a hazard ratio (HR) of 0.63 (P = .0001) for PFS and 0.76 (P = .0188) for OS compared with IFL-treated nonresponders. FOLFOX-treated nonresponders had an HR of 0.75 (P = .0029) for PFS and 0.74 (P = .0030) for OS compared with IFL-treated nonresponders.
CONCLUSION:
In both AVF2107g and N9741, objective response did not predict the magnitude of PFS or OS benefit from the superior therapy; nonresponders, despite a poorer prognosis than responders, achieved extended PFS and OS from BV plus IFL or FOLFOX compared with IFL. On the basis of these data, tumor response in metastatic colorectal cancer is not a necessary factor for a therapy to provide benefit to an individual patient.
Grothey A et al.
Response-independent survival benefit in metastatic colorectal cancer: a
comparative analysis of N9741 and AVF2107.
J Clin Oncol. 2008 Jan 10;26(2):183-9. PMID: 18182660