This article is more than 5 years old. Information may no longer be current.
Novel chemotherapy drug demonstrates activity in advanced breast cancer
Click Here to Manage Email Alerts
CHICAGO — The novel chemotherapy drug etirinotecan pegol demonstrated a trend toward improved survival compared with treatment of physician’s choice among patients with late-stage advanced breast cancer, according to findings from a phase 3 trial presented at the ASCO Annual Meeting.
Although treatment with etirinotecan pegol (NKTR-102; Nektar Therapeutics) did not reach the pre-determined statistically significant benefit in all patients, subgroups of patients — particularly those with brain or liver metastases — experienced significantly improved OS with etirinotecan pegol.
“Chemotherapy remains the backbone of management of many patients with advanced breast cancer,” Edith A. Perez, MD, Deputy Director at Large for the Mayo Clinic Cancer Center in Jacksonville, Florida, director of the Mayo Clinic Breast Cancer Translational Genomics program and a HemOnc Today Editorial Board member, said in an interview. “So we are looking for novel chemotherapy agents with better pharmacokinetics and no neuropathy to speak of and very little myelosuppression or cardiac toxicity.”
Etirinotecan pegol is the first long-acting topoisomerase 1 inhibitor that provides sustained levels of the active metabolite SN-38.
The BEACON study included 852 patients with advanced breast cancer who had any ER/HER-2 status. Perez and colleagues randomly assigned patients to receive etirinotecan pegol or a physician’s choice of standard chemotherapy. In the standard chemotherapy group, 40% of patients received eribulin, 23% received vinorelbine, 18% received gemcitabine, 15% received taxane and 4% received ixabepalone.
OS served as the primary endpoint.
The researchers observed a 2.1-month improvement in median OS with etirinotecan pegol (12.4 months) compared with treatment of physician’s choice (10.3 months) in the overall study population (HR = 0.87; P = .08).
In a pre-specified subgroup of patients with brain metastases (n = 67), those who received etirinotecan pegol achieved a median OS of 10 months, whereas those assigned treatment of physician’s choice achieved a 4.8-month median OS (HR = 0.51; P < .01).
Further, a larger proportion of patients with brain metastases who received etirinotecan pegol achieved 12-month OS than patients assigned physician’s choice (44.4% vs. 19.4%).
Etirinotecan pegol also demonstrated activity in patients with liver metastases (n = 456). Median OS improved in this subgroup for those treated with etirinotecan pegol was 10.9 months compared with 8.3 months for patients who received physician’s choice (HR = 0.73; P = .002).
“We demonstrated that in patients with liver or brain metastases, this drug improves survival in a statistical fashion,” Perez said. “This is very interesting because the toxicity was less in this novel chemotherapy drug compared to the standard chemotherapy drugs in the market that are utilized and the worsening of quality of life was less with this novel chemotherapeutic agent. In these 2 tough subgroups of patients that need some help, we saw some survival improvement.”
Fewer grade 3 or higher adverse events occurred among patients assigned etirinotecan pegol compared with physician’s choice (48% vs. 63%). The most common adverse events in the etirinotecan pegol arm were diarrhea (9.6%), neutropenia (9.6%), anemia (4.7%) and dyspnea (4.4%).
Severe neuropathy occurred in 3.7% of the patients in the physician’s choice arm and 0.5% of patients in the etirinotecan pegol arm. Alopecia occurred less frequently in the etirinotecan pegol group than in the physician’s choice group (10% vs. 23%).
“More studies are going to be needed, but if this drug were available now, we would really consider it for patients,” Perez said. “The company is having discussions with regulatory agencies about how to take this forward, but there’s a huge amount of interest in the setting of brain metastases because of the dramatic improvements in survival that we observed. I hope the company does a larger study that includes more patients with brain metastases because I think there is something here. This drug is active.”– by Anthony SanFilippo
Reference: Perez EA, et al. Abstract 1001 Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
For more information: Edith A. Perez, MD, can be reached at Mayo Clinic Cancer Center, 4500 San Pablo Road, Jacksonville, FL 32224; email: perez.edith@mayo.edu.
Disclosure: Perez reports no relevant financial disclosures. See the abstract for a complete list of the researchers’ relevant financial disclosures.
Perspective
Back to Top
Mateusz Opyrchal, MD, PhD
Perez and colleagues presented a very well-designed study with a novel chemotherapy agent, etirinotecan pegol, in patients with metastatic breast cancer resistant to standard chemotherapy treatments. This patient population is very difficult to treat as current options have relatively low response rates and high toxicity burden.
The overall study showed an overall 2.1-month median OS benefit, although it did not reach statistical significance. A pre-planned subgroup analysis showed an impressive median OS benefit of 5.2 months in patients with brain metastasis with 44.4% vs. 19.4% alive at 12 months. There also was a statistically significant 2.6-month benefit in patients with liver metastasis. The observation of benefit in central nervous system disease is supported by pre-clinical work that showed increased concentrations of the active metabolite in the CNS. This is a very exciting finding as this patient population has very limited treatment options. This fact is highlighted by the results presented also at ASCO showing that the whole-brain radiation was not effective in prolonging OS while having significant side effects (Brown, PD, et al. Abstract LBA4. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.).
Overall, this well-designed study shows a potential of this new compound in treatment of patients with advanced breast cancer. It has a different mechanism of action compared with current chemotherapy agents. The results are most exciting in a very difficult-to-treat group of patients with brain metastasis. I hope these promising results will encourage future clinical trials as it would be a very welcome new tool for treatment of patients.
Click Here to Manage Email Alerts