Carboplatin Desensitization Leads to Improved OS in Ovarian Cancer

Gary H. Altwerger, MD

Patients withBRCA-proficient ovarian cancer who were treated with a carboplatin desensitization regimen had an improved overall survival (OS), according to a retrospective analysis reported at the 2017 Society of Gynecologic Oncology Annual Meeting.

Patients withBRCA-proficient cancers and treated hypersensitivity had a median OS of 114 months compared with 71 months for patients withBRCA-proficient cancers and no carboplatin hypersensitivity. Carboplatin hypersensitivity had a strong association withBRCAdeficiency, but desensitization did not improve survival as compared with patients who did not have carboplatin hypersensitivity, Gary H. Altwerger, MD, a gynecologic oncology fellow at Yale University School of Medicine, and colleagues reported in a poster presentation.

“Patients who undergo carboplatin desensitization have better overall survival than patients who did not undergo the glucocorticoid and antihistamine regimen,” the investigators concluded. “Patients with germlineBRCA1/2proficiency and hypersensitivity who received carboplatin desensitization have better median overall survival compared with the same patients who do not have hypersensitivity. Importantly, there is no difference in median overall survival in patients with germlineBRCA1/2deficiencies when comparing patients with or without hypersensitivity.

“This study supports the use of a carboplatin desensitization protocol, as it is effective and safe at preventing hypersensitivity reactions and also improves overall survival in patients with advanced-stage ovarian cancer.”

A mainstay of treatment for ovarian cancer, carboplatin induces tumor cell death by means of DNA double-strand breaks. Double-strand breaks activate DNA repair mechanisms, including theBRCAhomologous recombination (HR) repair enzymes. Patients withBRCAmutations have better clinical outcomes when treated with carboplatin-containing chemotherapy, in part, because of the accumulation of DNA damage in HR-deficient patients, Altwerger and colleagues noted.

A potential downside to carboplatin therapy is hypersensitivity reactions after exposure to multiple cycles of therapy. Carboplatin desensitization protocols can quickly and efficiently prevent hypersensitivity reactions.

Previous research suggested an association between carboplatin, PARP inhibition,BRCAdeficiency, and hypersensitivity (Br J Cancer. 2013;109:1072-1078). Dr. Altwerger and colleagues investigated overall survival in patients withBRCA-deficient and proficient ovarian cancer and carboplatin hypersensitivity treated with a desensitization protocol.

The retrospective study included patients treated from August 2012 to January 2016. All patients underwent testing for germlineBRCAmutations. Treatment in all cases included carboplatin, and all patients were evaluated for carboplatin hypersensitivity during the seventh cycle of therapy and beyond.

The analysis included 40 patients withBRCA-deficient tumors and 51 withBRCA-proficient tumors. TheBRCA-deficient group included 8 patients with breast cancer.

Significantly more patients in theBRCA-deficient group had carboplatin hypersensitivity (31 versus 20 in theBRCA-proficient group,P=.0003).

The entire study population had a median OS of 127 months, 5-year OS of 72%, and 10-year OS of 51%. Patients withBRCAdeficiency had a significantly better median OS compared with theBRCA-proficient group (176 vs 83 months;P= .0249). Patients with treated carboplatin hypersensitivity had a median OS of 131 months compared with 83 months for patients without sensitivity to carboplatin (P= .0094).

EvaluatingBRCAstatus and hypersensitivity, investigators found that theBRCA-deficient group had a median OS of 176 months with treated carboplatin hypersensitivity versus 163 months without hypersensitivity, a nonsignificant difference. In contrast, patients withBRCAproficiency and treated carboplatin hypersensitivity had a median OS of 114 months compared with 71 months for patients without carboplatin hypersensitivity (P= .04943).

Comparison of clinical and demographic characteristics between carboplatin-hypersensitive and nonhypersensitive patients showed no significant differences in either theBRCA-deficient orBRCA-proficient group.

“We have shown that germlineBRCA1/2