Panitumumab(帕尼单抗)

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本帖最后由虎光着于 2018-8-24 18:55 编辑

Final results from study 181: Randomized phase III study of FOLFIRI with or without panitumumab (pmab) for the treatment of second-line metastatic colorectal cancer (mCRC).

Background: In the primary analysis of study 181, pmab+FOLFIRI significantly improved progression-free survival (PFS) vs FOLFIRI as second-line therapy in patients (pts) with wild-type (WT) KRAS mCRC. Here, we report the results of a prespecified final descriptive analysis planned for 30 months (mos) after the last pt was enrolled. Methods: Pts were randomised 1:1 to pmab 6.0 mg/kg Q2W+FOLFIRI (Arm 1) vs FOLFIRI alone (Arm 2). Pts had one prior fluoropyrimidine-based chemotherapy regimen for mCRC and ECOG 0-2. The co-primary endpoints were PFS (central assessment) and OS, and were independently tested. Secondary endpoints included objective response rate (ORR), and safety. KRAS status was determined by a blinded central lab. Results: 1,186 pts were randomised and received treatment (tx): 591 in Arm 1, 595 In Arm 2. 1,083/1,186 pts (91%) had KRAS results. Adverse event rates were consistent with the primary analysis. Results are shown in the table. Conclusions: In Arm 1, PFS (standard and on-treatment definition) and ORR were improved, and there was a trend toward improved OS in pts with WT KRAS mCRC. The large proportion of pts receiving post-progression anti-EGFR therapy may have affected the ability to observe a difference in OS between the tx arms. In pts with MT KRAS there was no difference in efficacy. KRAS testing is critical to select appropriate pts for tx with pmab.

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WT KRAS mCRC                                                       Arm 1                      Arm 2                      HR                p valuea
(n = 597)                                                                (n = 303)                   (n = 294)             (95%CI)
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Median PFS - mos (95% CI)                                  6.7 (5.8-7.4)                4.9 (3.8-5.5)       0.82 (0.69-0.97) 0.023
                                                                                                                                             0.73* (0.60-0.88)  0.001*
Median OS - mos (95% CI)                                     14.5 (13.0-16.1)       12.5 (11.2-14.2) 0.92(0.78-1.10) .366
ORRb - % (95%CI)                                                 36 (31-42)                10 (7-14)
Odds ratio (95%CI)                                                 5.50 (3.32-8.87)                                                                < 0.0001
MT KRAS mCRC                                                    Arm 1                         Arm 2
   (n = 486)                                                          (n = 238)                   (n = 248)
Median PFS - mos (95% CI)                                  5.3 (4.2-5.7)             5.4 (4.0-5.6)       0.95 (0.78-1.14) 0.561
Median OS - mos (95% CI)                                     11.8 (10.4-13.3)       11.1 (10.3-12.4) 0.93 (0.77-1.13) 0.482
ORRb - % (95% CI)                                              13 (9-18)                   15 (11-20)
Odds ratio (95% CI)                                              0.93 (0.53-1.63)                                                                   0.885
Pts receiving post-study anti-EGFR tx – n (%)       Arm 1                         Arm 2
WT KRAS                                                             38 (12.5)                   101 (34.4)
MT KRAS                                                                21 (8.8)                      79 (31.9)
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* On treatment; aDescriptive; bPts with baseline measurable disease per modified RECIST.

如同西妥昔单抗（爱必妥）一样，帕尼单抗仍然对于Kras的状态有收益性要求，即Kras状态为野生型才可获益。上述临床实验是在ASCO2012年初级会议上公布的帕尼单抗+FOLFIRI/FOLFIRI在二线治疗转移性结直肠癌方面的三期临床数据。从数据上来看，Kras野生型病患可以获得更多的收益，这也是与最新NCCN结论相吻合的。

帕尼单抗目前尚未在中国正式上市，国内有一些临床实验正在进行，需要这方面信息的病友可留意本论坛的新药临床贴。