Δευτέρα, 14 Δεκεμβρίου 2015

HRD AS PREDICTIVE FACTOR FOR PLATINUMUSE IN BREAST CANCER

Two studies evaluating the ability of myChoice HRD, a homologous recombination deficiency (HRD) test, to identify patients with breast cancer who are likely to respond to platinum-containing therapies have found that the test is effective in optimizing therapy selection for patients. The diagnostic test was used to evaluate homologous recombination deficiency as a predictive biomarker of response to neoadjuvant platinum-based therapy in patients with triple-negative breast cancer; and homologous recombination deficiency as a predictive biomarker of response to preoperative systemic therapy containing a platinum drug in patients with estrogen receptor–positive or triple-negative breast cancer.
The data were presented in two poster sessions, study P3-07-12, by Telli et al; and study P3-07-13 by Connolly et al, at the 2015 San Antonio Breast Cancer Symposium held on December 8-12.
P3-07-12 Study Methodology 
Patients with triple-negative breast cancer and known homologous recombination deficiency status from the following clinical trials were available for analysis: PrECOG 0105 (N = 72), NCT00148694/NCT00580333 (N = 50), NCT01372579 (N = 26), and TBCRC 008 (N = 18). Neoadjuvant chemotherapy regimens included (1) carboplatin, gemcitabine, iniparib; (2) cisplatin with or without bevacizumab (Avastin); (3) carboplatin, eribulin (Halaven); 4) carboplatin, nab-paclitaxel (Abraxane) with or without vorinostat (Zolinza).
Homologous recombination deficiency status was defined as a high homologous recombination deficiency score (42 or higher) and/or presence of a BRCA1/2 tumor mutation. Logistic regression models were used to adjust for study effects. The addition of data from the triple-negative breast cancer platinum-treated arm of GeparSixto (n = 101) to this pooled analysis brought the total sample size to 267 patients.
Study Results
Pathologic complete response was achieved in 51 patients (31%) and 104 patients (63%) were homologous recombination deficient (31 with high homologous recombination deficiency scores and BRCA1/2 mutation, 67 with high scores only, and 6 with BRCA1/2 mutation only). Patients with homologous recombination deficient tumors were more likely to achieve a pathologic complete response than those with homologous recombination nondeficient tumors: 44% vs 8% (< .01). When adjusting for study effects in separate logistic regression models, patients with homologous recombination deficient tumors (odd ratio = 12.5), with BRCA1/2 mutations irrespective of HRD score (odds ratio = 2.3), or with high homologous recombination deficiency scores (odds ratio = 14.6) were more likely to have a pathologic complete response.
Conclusion
Homologous recombination deficiency status is a robust predictor of pathologic complete response across different neoadjuvant platinum-based regimens. This pooled analysis suggests that homologous recombination deficiency can be used to identify triple-negative breast cancer patients with a high probability of obtaining pathologic complete response with a platinum-based neoadjuvant chemotherapy regimen.
P3-07-13 Study Methodology 
This study assessed the ability of myChoice HRD to predict pathologic complete response in 48 patients with breast cancer (30 with estrogen receptor–positive breast cancer and 18 with triple-negative breast cancer) who were treated with preoperative systemic therapy carboplatin and albumin-bound paclitaxel with or without vorinostat. The pathologic complete response rate was similar in both arms (vorinostat, 25.8%; placebo, 29%).
The researchers performed an exploratory biomarker study correlating baseline tumor biopsy homologous recombination deficiency status with pathologic complete response. The analysis population included all patients with available homologous recombination deficiency and pathologic complete response data.
They compared the proportion of patients with pathologic complete response by homologous recombination deficiency status using Fisher's exact test. A subset analysis compared pathologic complete response proportions by high (42) vs low (<42 deficiency="" did="" em="" have="" homologous="" in="" nbsp="" not="" patients="" recombination="" score="" style="border: 0px; font-family: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;" those="" who="">BRCA1/2
 mutation. A logistic regression model included homologous recombination deficiency status, estrogen receptor status, treatment arm, tumor grade, and use of additional anthracycline-based nonstudy chemotherapy prior to definitive surgery.
Study Results
The researchers found that 46% of tumors were homologous recombination deficient (n = 22/48, 33% estrogen receptor–positive [10/30], 67% triple-negative breast cancer [12/18]). They observed a significantly higher pathologic complete response rate in patients with homologous recombination deficiency vs not (50% vs 7.7%, P = .002) in the overall population.
A similar trend was observed in estrogen receptor–positive (30% vs 5%, P = .095) and triple-negative breast cancer (66.7% vs 16.7%, P = .13) patients. There was no significant difference when analyzed by treatment arm (vorinostat vs placebo).
In a subgroup analysis (n = 40) of patients without BRCA1/2 mutation (25 estrogen receptor–positive, 15 triple-negative breast cancer), a significantly higher pathologic complete response rate was observed in those with high vs low homologous recomination deficiciency score (64.3% vs 7.7%, P < .001). After adjusting for estrogen receptor status, randomized treatment, use of doxorubicin/cyclophosphamide treatment, and tumor grade, patients whose tumors exhibited homologous recombination deficiency had a greater than sixfold increase in pathologic complete response compared to those without homologous recombination deficiency (adjusted odds ratio = 6.76, 95% confidence interval = 0.85–53.99, P = .072).
Conclusion
The study authors concluded that their results support prior observations that homologous recombination deficiency status is a promising predictive biomarker of response to platinum agents in triple-negative breast cancer. “Further evaluation of this question is warranted in both [triple-negative breast cancer] and [estrogen receptor]-positive breast cancer,” wrote the authors.

Δεν υπάρχουν σχόλια: