Soft trial update

In stratified analysis, absolute benefit tended to be greater among women in TEXT who received chemotherapy 6. Exemestane plus OFS was also superior to tamoxifen plus OFS in terms of breast cancer—free interval, with an absolute 4. Overall survival did not differ significantly between arms. Francis said. Francis summarized. Session attendee Hope S. Francis replied, noting that analyses sorting out the reasons for early discontinuation are planned.

Satyajeet oesophagus management. Ca endometrium. Ca penis. Ca anal canal. Related Books Free with a 30 day trial from Scribd. Jen Gunter. Related Audiobooks Free with a 30 day trial from Scribd. Single On Purpose: Redefine Everything.

Find Yourself First. John Kim. Gundry, MD. Permission to Dream Chris Gardner. Presented by: Dr. Satyajeet Rath Guided by: Dr. Shantanu Sapru Date: Prudence A. Francis et al. Major controversial topics were, and still are: 1.

Is Tamoxifen TAM alone an optimal treatment? What is the role of ovarian function suppression OFS? The 8-year rate of being free of distant disease was Eight-year disease-free survival among these women went from Clearly, only a few of the disease-free survival events prevented or delayed by ovarian function suppression with or without using exemestane instead of tamoxifen were life-threatening.

The argument is very strong because the overwhelming majority of these women did very well, and it makes no sense to subject 99 women to the ravages of an early menopause to benefit 1 woman with delayed distant metastases. One suspects that these very low—risk women would derive little or no benefit from chemotherapy either as was noted in the TAILORx study.

We do not know exactly how the physicians and the patients chose those women to avoid chemotherapy, but we know they turned out to be older, had smaller primary tumors that were better differentiated, with few or no positive lymph nodes, and had cancers that were almost never HER2-positive.

We are left deciding whether the benefits to the higher-risk patients those selected to receive chemotherapy are worth the toxicities. In the SOFT trial, the benefit of adding ovarian function suppression to tamoxifen in this population is a 2. Using exemestane plus ovarian function suppression did reduce distant events compared with tamoxifen to Among chemotherapy-treated patients, exemestane plus ovarian function suppression led to a slightly worse overall survival than tamoxifen plus ovarian function suppression in the SOFT trial, but a slightly better one in the TEXT trial.

This may be due to chance, but it is more likely a reflection of study eligibility. Women in the TEXT trial, who entered before chemotherapy was started, were more likely to have permanent ovarian failure from their chemotherapy and to not depend only on the triptorelin Trelstar, Triptodur injections to shut down their ovarian endocrine function.

Since triptorelin does not always work, a drug like exemestane—which depends on nonsecreting ovaries—will work better in a study where more of the population has permanent ovarian failure without triptorelin. The SOFT trial was designed to demonstrate the effect of ovarian function suppression in women with functioning ovaries. Those with permanent ovarian failure were therefore excluded from SOFT, but not from TEXT where randomization and initiation of triptorelin, if assigned, was before chemotherapy.

The big problem is that the disease-free survival benefit to adding ovarian function suppression to tamoxifen is largely driven by the HER2-positive cases among the approximately 2, patients in the comparison.

The hazard ratio for disease-free survival for adding ovarian function suppression is 0. Given this finding, it is surprising that disease-free survival improvement for exemestane plus ovarian function suppression over tamoxifen was not greater in the HER2-positive population than in the HER2-negative one.

I have not heard a convincing explanation for this observation beyond the play of chance. Since we now segregate HER2-positive cancers and treat them differently, we need to see outcomes for distant recurrence-free interval and overall survival among women with higher-risk disease who were given chemotherapy and whose cancers were negative for HER2.

For women with HER2-negative cancers in both the SOFT and TEXT trials who received chemotherapy, distant recurrence—free interval favored exemestane plus ovarian function suppression over tamoxifen plus ovarian function suppression, with a hazard ratio of about 0. Overall survival among all HER2-negative patients with or without chemotherapy favored exemestane plus ovarian function suppression over tamoxifen plus ovarian suppression, with a hazard ratio of 0. The 8-year overall survival advantage for exemestane over tamoxifen each plus ovarian function suppression in TEXT was 1.

Only longer follow-up will tell us whether the encouraging differences in distant recurrence—free interval favoring exemestane plus ovarian function suppression over tamoxifen plus ovarian function suppression translate into a long-term significant advantage in overall survival. Until then, we are left with the surrogate endpoint of distant recurrence—free interval.

We have not yet seen analyses of distant recurrence—free interval and overall survival for all three arms of SOFT for the HER2-negative, chemotherapy-treated population. Download a trial version of Payroll Manager. The trial runs for a month and any data you create will be useable in the full version should you continue.

Download the latest Payroll Manager update. Your current payroll data will not be affected by the download. For downloading Payroll Manager for the first time or for installing on a new computer — requires a user licence code ULC.