Durable Clinical Activity to the AKT Inhibitor Ipatasertib in a Heavily Pretreated Patient With an AKT1 E17K Mutant Metastatic Breast Cancer

122 Background: In recent years many drug combinations have demonstrated clinical activity in heavily pretreated patients (pts) with metastatic breast cancer (MBC). Eribulin (E) in monotherapy has shown a beneficial effect in overall survival (OS) with slight rate of objective responses (OR) and poor effect in progression free survival (PFS). The Eribulin – Carboplatin (Cb) combination has been studied in other types of tumors in a phase Ib with promising results. We initiated an exploratory program with an off-label combination of E – Cb in pts with visceral disease and ECOG < 2. Methods: We retrospectively analyzed pts with MBC previously treated with anthracyclines, taxanes, and Capecitabine. Chemotherapy regimen consisted of E 1.1mg/m2 on days 1 and 8 and Cb AUC: 5 on day 1 every 21 days. Toxicity was assessed according to CTC criteria v 4.0. OR, PFS and OS rates were also evaluated. RECIST criteria were used to appraise radiological response. Results: Treatment was delivered in 10 pts. Median (M) age was 56 (range, 39-65). Pts characteristics were defined as follows: ECOG 0 (1 pt), 1 (6 pts) and 2 (3 pts); histological subtypes: luminal 9 pts and Her-2, 1 pt. M of previous lines was 7 (3-11). M of metastatic localizations were 3 (1-4). M of administered cycles was 6’5 (1-10). Grade 2 toxicity was asthenia 40%, peripheral neuropathy 10% and nausea - vomiting 10%. G 3 anemia and thrombopenia were noted in 20%. G 3-4 neutropenia was observed in 5 pts. Two pts required hospital admission due to febrile neutropenia. OR rate: complete response 10%, partial response 50% and stable disease 40%. Biochemical response rate was 80%. M of follow-up was 11 months, with M PFS and OS of 8 (4-11) and 18 months (4-18) respectively. Conclusions: Eribulin and Carboplatin is feasible, achieving remarkable response and survival rates with an acceptable toxicity profile in heavily pretreated patients with metastatic breast cancer. Preliminary results are promising and encourage us to continue recruiting patients.

Download Full-text

Lapatinib and capecitabine in a heavily-pretreated patient with HER2-positive metastatic breast cancer

10.5348/100007c01ma2018cr ◽

2020 ◽

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Her2 Positive ◽

Pretreated Patient ◽

Heavily Pretreated

Download Full-text

Trastuzumab and Gemcitabine in Pretreated HER2 Overexpressing Metastatic Breast Cancer Patients: Retrospective Analysis of Our Series

Journal of Oncology ◽

10.1155/2012/198412 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Vincenzo Di Lauro ◽

Elena Torrisi ◽

Ettore Bidoli ◽

Daniela Quitadamo ◽

Sara Cecco ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Response Rate ◽

Target Therapy ◽

Metastatic Breast ◽

Clinical Activity ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Heavily Pretreated

Trastuzumab-based regimes improved clinical outcome in women with overexpressing HER2 metastatic breast cancer, mainly due to the availability of different combination therapies, clinically active and well tolerated. In this study we retrospectively evaluated clinical activity and toxicity of trastuzuamb plus gemcitabine regimen in heavily pretreated HER2 positive metastatic breast cancer patients. Although the observed population was heavily pretreated, the evaluated regimen was notably effective in terms of response rate, time to progression and survival, with very mild toxicity. These data suggest that in over expressing HER2 metastatic breast cancer patients, sequential trastuzumab based chemotherapeutic regimens can achieve good response rate with prolonged TTP in responding patients, even after other target therapy such as lapatinib based combinations.

Download Full-text

Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.8.2056 ◽

1995 ◽

Vol 13 (8) ◽

pp. 2056-2065 ◽

Cited By ~ 85

Author(s):

J S Abrams ◽

D A Vena ◽

J Baltz ◽

J Adams ◽

M Montello ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Progressive Disease ◽

Overall Response Rate ◽

Metastatic Breast ◽

Investigational Drug ◽

Single Institution ◽

Doxorubicin Treatment ◽

Heavily Pretreated ◽

Pretreated Patients

PURPOSE To provide paclitaxel, an investigational drug at the inception of this study, to women with chemotherapy-refractory metastatic breast cancer and to evaluate response and toxicity in these patients. PATIENTS AND METHODS Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastatic breast cancer and a contraindication to further doxorubicin treatment received paclitaxel either at 175 mg/m2 intravenously (IV) over 24 hours or at 135 mg/m2 if they had prior irradiation to 30% of marrow-bearing bone or a cumulative dose of mitomycin > or = 20 mg/m2. RESULTS In a subgroup of patients (n = 172) with measurable disease, four complete responses (CRs) and 36 partial responses (PRs) occurred, for an overall response rate of 23% (95% confidence interval [CI], 17% to 30%). No differences in response rates were noted according either to the number of prior chemotherapy regimens received or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutropenia in 45% of patients and a hospitalization rate of 49%. CONCLUSION Paclitaxel's activity in this multiinstitutional trial in heavily pretreated patients confirms the encouraging results attained in single-institution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative care, supportive measures such as colony-stimulating factors and antibiotics were not used prophylactically. Current research efforts are focusing on whether paclitaxel's activity against breast cancer is dose- and/or schedule-dependent, and on what role it has in patients with less advanced disease.

Download Full-text

Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.66.130 ◽

2005 ◽

Vol 23 (23) ◽

pp. 5314-5322 ◽

Cited By ~ 347

Author(s):

Stephen Chan ◽

Max E. Scheulen ◽

Stephen Johnston ◽

Klaus Mross ◽

Fatima Cardoso ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Adverse Events ◽

Dose Level ◽

Locally Advanced ◽

Metastatic Breast ◽

Heavily Pretreated ◽

Pretreated Patients ◽

Grade 3 ◽

Time To Tumor Progression

Purpose In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated. Patients and Methods Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus. Results Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%). Conclusion In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.

Download Full-text