一线化疗后转易瑞莎对比继续化疗的新结果(日本结果)--对腺癌可显著延长生存期

jimmy112199

这是发表于2008年癌症年会的日本的文献，介绍了他们对比一线化疗后转向IRESSA方案和继续化疗方案的三期试药结果。结果显示：对腺癌患者，无进展生存期增长了30%。

Randomized phase III study of platinum-doublet chemotherapy followed by gefitinib versus continued platinum-doublet chemotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC): Results of West Japan Thoracic Oncology Group trial (WJTOG.
Sub-category:
Metastatic Lung Cancer
Category:
Lung Cancer--Metastatic Lung Cancer
Meeting:
       
2008 ASCO Annual Meeting
Abstract NoBA8012
Citation:J Clin Oncol 26: 2008 (May 20 suppl; abstr LBA8012)
Author(s):T. Hida, I. Okamoto, T. Kashii, M. Satouchi, Y. Ichinose, N. Katakami, M. Ando, T. Kurata, K. Nakagawa, M. Fukuoka
Abstract:
Background: Gefitinib is a small molecule inhibitor of the EGFR tyrosine kinase. When combined with chemotherapy, no survival gain was observed compared to chemotherapy alone (INTACT I and II). We have conducted a randomized phase III trial to evaluate whether gefitinib improves survival as maintenance therapy after platinum-doublet chemotherapy in pts with advanced NSCLC. Methods: Chemotherapy-na&#239;ve pts with advanced stage (IIIB/IV) NSCLC, ECOG PS of 0-1, and adequate organ functions were randomized to either, A) platinum-doublet chemotherapy (Carboplatin AUC 6+Paclitaxel 200mg/m2 day1 Q3w, Cisplatin 80mg/m2 day1+Irinotecan 60mg/m2 day1,8,15 Q4W, Cisplatin 80mg/m2 day1+Vinorelbine 25mg/m2 day1,8 Q3W, Cisplatin 80mg/m2 + Docetaxel 60mg/m2 day1 Q3W, or Cisplatin 80mg/m2 day1+Gemcitabine 1,000mg/m2 day1, 8 Q3W) up to 6 cycles or B) platinum-doublet chemotherapy for 3 cycles followed by gefitinib 250 mg orally once daily. Pts were stratified by disease stage, gender, histology and chemotherapy regimens. The primary endpoint was overall survival (OS); secondary endpoints include progression-free survival (PFS), response rate (RR), safety and QOL. A sample size of 300 pts per group was estimated on the basis of a projected median survival of 9 months (m) in arm A and 11.4 m in arm B, with a power of 80% at 0.05 two-sided alpha to compare both group. Results: 603 pts were randomized between March 2003 and May 2005, and pt characteristics were equally distributed between arms. There was a statistically significant improvement in PFS (HR, 0.68; 95% CI, 0.57- 0.80; P<0.001) in arm B; however, OS result did not reach statistical significance (P=0.10). In a pre-specified analysis of OS by histologic groups, arm B had significantly better OS than arm A in adenocarcinoma histology (n=467; HR, 0.79; 95% CI, 0.65-0.98; P=0.03). Conclusions: These results demonstrate a possible clinical benefit for maintenance therapy of gefitinib, especially in adenocarcinoma histology.

[ 本帖最后由 jimmy112199 于 2008-10-28 14:38 编辑 ]

jimmy112199

Trial of Ongoing Chemo vs. Switch to Iressa for Japanese Patients with Advanced NSCLC

An interesting trial presented at ASCO 2008 came out of Japan, asking the question of whether there is an advantage to continuing first line platinum-based doublet chemo for up to six cycles or whether it might be better to give just three cycles and then switch from chemo right to the EGFR inhibitor iressa in Japanese patients with advanced NSCLC (abstract here). I haven’t mentioned it before because the trial, although interesting and with some provocative findings, didn’t clearly provide conclusions that would lead to obvious management changes.

For trial 0203, the West Japan Thoracic Oncology Group (WJTOG) enrolled 600 patients with previously untreated advanced NSCLC, with asymptomatic brain metastases permitted. Unlike North American NSCLC patients, among whom 10-15% are never-smokers, 31% of the patients in this Japanese trial were never-smokers; about 78% had adenocarcinomas (a higher proportion than in North America or Europe). They were randomized to receive chemo for six cycles vs. three followed by Iressa. The chemo could be carbo/taxol or cisplatin with gemcitabine, taxotere, navelbine, or irinotecan, all comparable in activity.

The study was looking for a significant improvement in overall survival from the early switch to iressa, and it showed a strong trend in that direction, but it wasn’t a statistically significant difference:

WJTOG 0203 OS (Click to enlarge)

There was, however, a very significant improvement (over 30%) of progression-free survival with the early transition to iressa:

WJTOG 0203 PFS

Interesting, and perhaps worth considering changing practice for appropriate patients.  But I wouldn’t generalize results from a Japanese study to a non-Asian population: I think it’s becoming increasingly clear that lung cancer in Japanese patients is a somewhat different disease than what we tend to see in the US.

The results of a subset analysis of this trial highlight this more clearly.  Interestingly, as shown in the following curves (which are small, so click to enlarge and see better), there weren’t significant differences in the two trial arms among the never-smokers, although they had a median survival of 21-23 months, compared with the 10-11 month range for smokers, in whom the iressa arm had a significantly longer median survival:

WJTOG 0203 subsets all

It’s perhaps a little puzzling that the smokers had the significant benefit from an early switch to iressa, but my suspicion is that nearly all never-smokers got iressa and most received a major benefit from it, whether they received it earlier or later.  Perhaps the smokers were less likely to receive iressa if it wasn’t part of the trial but did benefit if they did receive it.  But the curves at the bottom of the slide above are also quite interesting, because they show that the smokers with non-adenocarcinomas did better with chemo for six full cycles, while the smokers with adeno NSCLC did better with an early switch to iressa.  This same trend held up when all patients on the trial were included:

WJTOG adeno vs. non-adeno

And the median survival in the adenocarcinoma patients is nearly twice as long as that in the non-adenocarcinoma patients.

As I mentioned above, I don’t think these results are generalizable to the world population, but I might consider these findings for my Asian patients.  I would emphasize that this trial doesn’t say that patients with non-adenocarcinoma NSCLC do worse with an EGFR inhibitor than if they never get one, but it suggests to me that (Asian) patients with adenocarcinomas may benefit from relatively early EGFR inhibitor (or at least a guarantee of getting it), while the patients with non-adenocarcinoma may benefit from more than the three initial cycles of platinum doublet chemo before switching to an EGFR inhibitor.

This study also provides another example of potentially optimized results by individualizing treatments for different subgroups, and the importance of clarifying the NSCLC subtype.  It doesn’t change my routine treatment approach today, but I think it’s the future.

ivor0514

好消息！要是能够解决耐药的问题就更好啦！

genghaisheng

是好消息！能够解决耐药的问题吗？看不懂内容