I just returned from the American Society of Clinical Oncology's Annual Meeting in Orlando, FL. It was an exiciting meeting, particularly for women's cancers.
I just returned from the American Society of Clinical Oncology's Annual Meeting in Orlando, FL. It was an exiciting meeting, particularly for women's cancers. There were exciting and new developments in breast and gynecologic cancers, and it will probably be impossible to highlight some of the most interesting findings in gynecologic cancers, but here it goes.
Ovarian Cancer: Following CA-125 or not?
Rustin, et al. presented the results of a very provocative and important study in the follow-up of ovarian cancer. The basic question he sought to address was how we follow and treat women with relapsed ovarian cancer. The current standard is to follow women in remission from ovarian cancer with CA-125 levels at three month intervals. However, until now, there was no evidence that using the CA-125 to dictate treatment that resulted in improved survival outcomes.
The MRC OV05/EORTC 55955 trial enrolled over 1440 women between May 1996 and August 2005. All had a diagnosis of ovarian cancer and were in clinical complete remission. The trial was designed to show a 10% improvement in two-year overall survival if treatment was given for an abnormal CA-125 (versus delaying treatment for signs/symptoms of recurrent disease). Of the 1440+ women registered, 529 (37%) were randomized to the strategy of treating based on CA-125 (early treatment) versus treatment only when disease became evident (delayed treatment). For the entire cohort, the median overall survival was 70.8 months. Of those that were randomized (n=529): Rustin reported women in the early treatment arm started their next therapy 0.8 months following randomization, versus 5.6 months in the delayed arm, which was statistically significant. Despite this, there was no benefit in overall survival demonstrated and the Hazard Ratio was 1.0. What did occur was a decline in the quality of life of patients—this was seen in those treated early.
This is the first trial to prospectively demonstrate that there is no advantage to early treatment of asymptomatic recurrence, solely based on CA-125. Rustin encouraged the audience to cease checking CA-125, and monitor only clinically. This is a paradigm that is used in the treatment of breast cancer, where following tumor markers has never shown a benefit to patients, so in that sense these findings are not altogether surprising. Still, for those of us who treat ovarian cancer, the CA-125 is very important, to both patients and providers. What this study tells us, though, is that while a rising marker may herald disease recurrence, women can have a good five months to prepare for the next round of chemotherapy, to adjust to the idea of living with ovarian cancer as a chronic disease, and to engage with their doctors into a treatment strategy that makes sense to them.
Combination chemotherapy in cervical cancer
Duenas-Gonzales, et al. presented a study performed in Latin America, which looked at a more intensive regimen for the treatment of cervical cancer. In this study, women with node-negative locally advanced cervical cancer [Stage IIB-IVA], were randomized to the current standard of chemoradiation using cisplatin versus an experimental regimen of chemoradiation using Cisplatin at the standard dose of 40mg /m2 followed by Gemcitabine at a dose of 125 mg/m2 during radiation therapy, followed by two cycles of cisplatin 50mg/m2 (D1) and gemcitabine 1000 mg/m2 (D1 and D8) adjuvantly, given four weeks after completion of radiation therapy. Remarkably, the study enrolled 515 women in two years. Duenas-Gonzales reported that combination therapy using gemcitabine resulted in improvements in both progression free survial three years (74% in the experimental arm vs. 65% in the standard arm, p=.023) and overall survival (78% vs. 69%, respectively p=.022). This came at a cost of increased grade 3-4 serious toxicities, where the incidence was 86.5% in the experimental arm, and 46.3% in the standard arm.
This is an important trial that appears to improve on the current accepted standard of single agent cisplatin-based chemoradiation. Still, it's unclear whether the gemcitabine contributed the difference, or the adjuvant cycles at the end of radiotherapy. Additionally, in order to be more fully utilized, the toxicity (acute only was reported) needs to be addressed, as this level is not likely to be acceptable. Indeed, further follow-up for delayed or late toxicity will be important to truly understand the impact of this agressive regimen on long-term quality of life. It is likely that a confirmatory trial will be needed prior to adoption of this regimen (or something similar) in the near future.
Getting away from paclitaxel: Survival results from the CALYPSO Trial
E. Pujade-Lauraine, et al. presented a trial in platinum-sensitive ovarian cancer, in which participants were randomized to pegylated liposomal doxorubin 30 mg/m2 + Carboplatin AUC 5 given every four weeks (experimental arm) versus Carboplatin AUC 5 + paclitaxel 175 mg/m2 given every three weeks (standard arm). The study was designed as a non-inferiority study to show that the use of a non-taxane regimen in platinum sensitive disease would be a reasonable alternative to standard treatment. Over 900 women participated in this trial, of which 99% had received prior taxane therapy and approximately 1/3rd had an intermediate platinum-sensitive status (platinum-free interval of 6-12 months). Regarding treatment in the experimental versus standard arms, experimental treatment was associated with longer treatment durations (21 vs. 16 weeks in the standard arm), less Grade 3-4 neutropenia (35% vs. 46%, p=.01), less alopecia (7% vs 84%), and interestingly, less hypersensitivity reactions (5% vs 19%, p<.001). At a median follow-up of 22 months, the median PFS was 11.3 months in the carboplatin/pegylated liposomal doxorubicin arm versu 9.4 months in the standard arm of carboplatin and pacltiaxel. This translated into an 18% improvement in progression-free survival favoring the experimental arm, which was significant and in fact, was superior to the standard arm (p=.005). In multivariate analysis, treatment came out as an independent predictor of progression-free survival.
This has the capacity to change the standard of care in the treatment of recurrent ovarian cancer. It points to a more tolerable and more active regimen, which can save women from potential toxicities inherent with paclitaxel, including alopecia and neuropathy.
There were several more trials worth mentioning, but I think I will save it for my second post in June!
Until then: DSD