Letrozole promising as maintenance treatment for high-grade serous ovarian cancer

Maintenance therapy with an aromatase inhibitor may improve progression-free survival in women with estrogen receptor (ER)–positive, high-grade serous ovarian cancers, results of a non-randomized, single-center study suggest.

Patients who received letrozole after debulking surgery and platinum-based chemotherapy had a significantly prolonged recurrence-free interval, compared with patients who declined the treatment, investigators reported in Gynecologic Oncology.

The benefit of letrozole maintenance treatment was also apparent in women with residual disease who received bevacizumab maintenance treatment, wrote first author Viola Heinzelmann-Schwarz, MD, of the Gynecological Cancer Center, University of Basel, Switzerland, and her coauthors.

The results “strongly suggest that endocrine maintenance therapy has more advantage than disadvantage for use in ovarian cancer patients and seems clearly justified,” when considered alongside other data regarding the potential benefit of letrozole in other treatment settings, Dr. Heinzelmann-Schwarz and her colleagues said.

“In contrast to available expensive maintenance medications like antiangiogenic [drugs] and PARP inhibitors, antihormonal drugs have a favorable safety profile, low cost, easy intake regimen with one tablet daily and an established prognostic target,” they added.

While the role of aromatase inhibitor maintenance therapy in high-grade serous ovarian cancer is unclear, previous studies have shown that patients with low-grade serous ovarian cancer may benefit from endocrine therapy.

Those studies in low-grade serous ovarian cancer include several small case series, and one retrospective analysis showing improved progression-free survival among women treated with endocrine therapy versus women who received observation only (J Clin Oncol. 2017 Apr. doi: 10.1200/JCO.2016.71.0632).

The more recent report by Dr. Heinzelmann-Schwarz and her colleagues included 50 women with ER-positive, FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stage III/IV high-grade serous ovarian cancer who were offered off-label letrozole treatment after debulking surgery and platinum-based chemotherapy. Twenty-three received letrozole maintenance treatment, and 27 declined.

In the group of women who received letrozole maintenance treatment, 60% were recurrence free at 24 months, compared with 38.5% of patients in the observation group (P = .035).

“This positive effect could particularly be seen when the treatment was initiated within 3 months after the end of adjuvant chemotherapy,” Dr. Heinzelmann-Schwarz and her coauthors wrote.

Among women with residual disease who received maintenance bevacizumab in addition to letrozole, 87.5% were recurrence free at 12 months, compared with 20.8% of patients who received bevacizumab only, the investigators said.

Minor side effects such as hot flushes, fatigue, and bone pain led to discontinuation in two patients (6.4%), and no serious adverse effects were seen during treatment, according to investigators.

Almost half of all high-grade serous ovarian cancers express ER, according to results of separate retrospective analyses also described by Dr. Heinzelmann-Schwarz and her colleagues in Gynecologic Oncology. They found that ER expression was similar regardless of drug resistance status (platinum sensitive versus platinum resistant) or treatment setting (primary or recurrent).

Dr. Heinzelmann-Schwarz and colleagues declared no conflicts of interest.

SOURCE: Heinzelmann-Schwarz V et al. Gyn Oncol. 2018 Jan. doi: 10.1016/j.ygyno.2017.10.036.

Maintenance therapy with an aromatase inhibitor may improve progression-free survival in women with estrogen receptor (ER)–positive, high-grade serous ovarian cancers, results of a non-randomized, single-center study suggest.

Patients who received letrozole after debulking surgery and platinum-based chemotherapy had a significantly prolonged recurrence-free interval, compared with patients who declined the treatment, investigators reported in Gynecologic Oncology.

The benefit of letrozole maintenance treatment was also apparent in women with residual disease who received bevacizumab maintenance treatment, wrote first author Viola Heinzelmann-Schwarz, MD, of the Gynecological Cancer Center, University of Basel, Switzerland, and her coauthors.

The results “strongly suggest that endocrine maintenance therapy has more advantage than disadvantage for use in ovarian cancer patients and seems clearly justified,” when considered alongside other data regarding the potential benefit of letrozole in other treatment settings, Dr. Heinzelmann-Schwarz and her colleagues said.

“In contrast to available expensive maintenance medications like antiangiogenic [drugs] and PARP inhibitors, antihormonal drugs have a favorable safety profile, low cost, easy intake regimen with one tablet daily and an established prognostic target,” they added.

While the role of aromatase inhibitor maintenance therapy in high-grade serous ovarian cancer is unclear, previous studies have shown that patients with low-grade serous ovarian cancer may benefit from endocrine therapy.

Those studies in low-grade serous ovarian cancer include several small case series, and one retrospective analysis showing improved progression-free survival among women treated with endocrine therapy versus women who received observation only (J Clin Oncol. 2017 Apr. doi: 10.1200/JCO.2016.71.0632).

The more recent report by Dr. Heinzelmann-Schwarz and her colleagues included 50 women with ER-positive, FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stage III/IV high-grade serous ovarian cancer who were offered off-label letrozole treatment after debulking surgery and platinum-based chemotherapy. Twenty-three received letrozole maintenance treatment, and 27 declined.

In the group of women who received letrozole maintenance treatment, 60% were recurrence free at 24 months, compared with 38.5% of patients in the observation group (P = .035).

“This positive effect could particularly be seen when the treatment was initiated within 3 months after the end of adjuvant chemotherapy,” Dr. Heinzelmann-Schwarz and her coauthors wrote.

Among women with residual disease who received maintenance bevacizumab in addition to letrozole, 87.5% were recurrence free at 12 months, compared with 20.8% of patients who received bevacizumab only, the investigators said.

Minor side effects such as hot flushes, fatigue, and bone pain led to discontinuation in two patients (6.4%), and no serious adverse effects were seen during treatment, according to investigators.

Almost half of all high-grade serous ovarian cancers express ER, according to results of separate retrospective analyses also described by Dr. Heinzelmann-Schwarz and her colleagues in Gynecologic Oncology. They found that ER expression was similar regardless of drug resistance status (platinum sensitive versus platinum resistant) or treatment setting (primary or recurrent).

Dr. Heinzelmann-Schwarz and colleagues declared no conflicts of interest.

SOURCE: Heinzelmann-Schwarz V et al. Gyn Oncol. 2018 Jan. doi: 10.1016/j.ygyno.2017.10.036.

Maintenance therapy with an aromatase inhibitor may improve progression-free survival in women with estrogen receptor (ER)–positive, high-grade serous ovarian cancers, results of a non-randomized, single-center study suggest.

Patients who received letrozole after debulking surgery and platinum-based chemotherapy had a significantly prolonged recurrence-free interval, compared with patients who declined the treatment, investigators reported in Gynecologic Oncology.

The benefit of letrozole maintenance treatment was also apparent in women with residual disease who received bevacizumab maintenance treatment, wrote first author Viola Heinzelmann-Schwarz, MD, of the Gynecological Cancer Center, University of Basel, Switzerland, and her coauthors.

The results “strongly suggest that endocrine maintenance therapy has more advantage than disadvantage for use in ovarian cancer patients and seems clearly justified,” when considered alongside other data regarding the potential benefit of letrozole in other treatment settings, Dr. Heinzelmann-Schwarz and her colleagues said.

“In contrast to available expensive maintenance medications like antiangiogenic [drugs] and PARP inhibitors, antihormonal drugs have a favorable safety profile, low cost, easy intake regimen with one tablet daily and an established prognostic target,” they added.

While the role of aromatase inhibitor maintenance therapy in high-grade serous ovarian cancer is unclear, previous studies have shown that patients with low-grade serous ovarian cancer may benefit from endocrine therapy.

Those studies in low-grade serous ovarian cancer include several small case series, and one retrospective analysis showing improved progression-free survival among women treated with endocrine therapy versus women who received observation only (J Clin Oncol. 2017 Apr. doi: 10.1200/JCO.2016.71.0632).

The more recent report by Dr. Heinzelmann-Schwarz and her colleagues included 50 women with ER-positive, FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stage III/IV high-grade serous ovarian cancer who were offered off-label letrozole treatment after debulking surgery and platinum-based chemotherapy. Twenty-three received letrozole maintenance treatment, and 27 declined.

In the group of women who received letrozole maintenance treatment, 60% were recurrence free at 24 months, compared with 38.5% of patients in the observation group (P = .035).

“This positive effect could particularly be seen when the treatment was initiated within 3 months after the end of adjuvant chemotherapy,” Dr. Heinzelmann-Schwarz and her coauthors wrote.

Among women with residual disease who received maintenance bevacizumab in addition to letrozole, 87.5% were recurrence free at 12 months, compared with 20.8% of patients who received bevacizumab only, the investigators said.

Minor side effects such as hot flushes, fatigue, and bone pain led to discontinuation in two patients (6.4%), and no serious adverse effects were seen during treatment, according to investigators.

Almost half of all high-grade serous ovarian cancers express ER, according to results of separate retrospective analyses also described by Dr. Heinzelmann-Schwarz and her colleagues in Gynecologic Oncology. They found that ER expression was similar regardless of drug resistance status (platinum sensitive versus platinum resistant) or treatment setting (primary or recurrent).

Dr. Heinzelmann-Schwarz and colleagues declared no conflicts of interest.

SOURCE: Heinzelmann-Schwarz V et al. Gyn Oncol. 2018 Jan. doi: 10.1016/j.ygyno.2017.10.036.