Simon Spazzapan

Hormone therapy in elderly breast cancer patients with comorbidities

Life-expectancy and comorbid conditions must be considered in the process of treatment decision-making for elderly patients affected by breast cancer both in the adjuvant and metastatic settings. Moreover, the choice of adjuvant treatment in all age groups is based on two main points: endocrine responsiveness and risk of relapse without setting an upper age limit. The hormonal therapeutic armamentarium of the medical oncologist is now open to different options that may best be tailored to different clinical situations, particularly in elderly women.

Lapatinib-based therapy in heavily pretreated HER2-positive metastatic breast cancer: a single institution experience

AIMS AND BACKGROUNDnLapatinib in combination with capecitabine is feasible in patients with HER2-positive metastatic breast cancer pretreated with anthracyclines, taxanes and trastuzumab, but inferior results were reported in the global lapatinib expanded access program in comparison with the phase III registration trial.nnnMETHODSnand study design. Women with HER2-positive metastatic breast carcinoma after antracycline, taxane and trastuzumab-based regimens were treated at progression with lapatinib plus capecitabine. The outcome of these patients was evaluated. From April 2007 to August 2010, 68 patients were treated overall.nnnRESULTSnMedian progression-free survival was 6 months (range, 1-29), and median overall survival was 26 months (range, 1-39). Eight (12%; 95% CI, 4-25) patients experienced a complete response. Partial response was observed in 22 patients (31%; 95% CI, 20-42), for an overall response rate of 43% (95% CI, 31-55). The treatment with lapatinib plus capecitabine was well tolerated, with grade 3-4 toxicity reported in few patients, and no treatment-related deaths were noted. Of note, no cardiac toxicity was reported in this highly pretreated group of patients or in the subgroup of 10 elderly patients.nnnCONCLUSIONSnOur data confirm that lapatinib plus capecitabine is an active regimen even in heavily pretreated patients with visceral and brain metastases and is feasible and active also in selected elderly patients.

Radical radiation therapy for oligometastatic breast cancer: Results of a prospective phase II trial

BACKGROUND AND PURPOSEnWe conducted a prospective phase II multicentric trial to determine if radical radiation therapy to all metastatic sites might improve the progression-free survival (PFS) in oligometastatic breast cancer patients. Secondary endpoints were local control (LC), overall survival (OS) and toxicity.nnnMETHODS AND MATERIALSnInclusion criteria were the following: oligometastatic breast cancer with ≤5 metastatic sites, FDG-PET/CT staging, no brain metastases, primary tumor controlled. Radiotherapy could be delivered using stereotactic body radiotherapy (SBRT) technique or fractionated intensity modulated radiotherapy (IMRT). SBRT consisted of 30-45Gy in 3 fractions, while IMRT was delivered to a total dose of 60Gy in 25 fractions. We hypothesized that radical radiation therapy could increase the PFS from 30% (according to the published literature) to 50% at two years.nnnRESULTSn54 Patients with 92 metastatic lesions were enrolled. Forty-four were treated with SBRT, and 10 with IMRT. Forty-eight (89%) patients received a form of systemic therapy concomitantly to radiation therapy. Sites of metastatic disease were the following: bones 60 lesions, lymph nodes 23 lesions, lung 4 lesions, liver 5 lesions. After a median follow-up of 30months (range, 6-55months), 1- and 2-year PFS was 75% and 53%, respectively. Two-year LC and OS were 97% and 95%, respectively. Radiation therapy was well tolerated, and no Grade ≥3 toxicity was documented. Grade 2 toxicity were pain and fatigue in 2 cases.nnnCONCLUSIONSnPatients with oligometastatic breast cancer treated with radical radiotherapy to all metastatic sites may achieve long-term progression-free survival, without significant treatment-related toxicity. While waiting for data from randomized trials, the use of radical radiation therapy to all metastatic sites in patients with oligometastatic breast cancer should be considered a valuable option, and its recommendation should be individualized.

Organ preservation in locally advanced head and neck cancer of the larynx using induction chemotherapy followed by improved radiation schemes

The present prospective study seeks to evaluate overall and disease free survival, response and organ preservation rate, and toxicity of an intensive chemotherapy regimen (CT) followed by unconventional radiotherapy (RT) in patients with locally advanced operable head and neck cancer. Between January 1998 and December 2006 (June 2005), 115 patients with locally advanced, operable head and neck cancer were evaluated. A total of 333 cycles of neoadjuvant CT (cisplatin–5FU, days 1, 14, 28) followed by hyperfractionated/accelerated radiotherapy were given to 108 patients. A total of 108 patients were evaluable and received the planned CT–RT treatment. Two months after the end of RT, 97.2% of patients had a clinical complete remission of the primary and 67.5% of the neck node site. The overall survival was 55% and cause-specific survival was 73% at 5xa0years. Of the 33 relapsed patients, 12 recurred only at the primary site and 10 patients had distant metastases. The overall organ preservation rate was 73.5%. The chemotherapy regimen reported an overall cardiotoxicity from 5FU in 14% of patients, with severe toxicity in 3%. The radiotherapy schedule developed 84% of Grade 3–4 mucositis in the observed patients. The accelerated CT–RT regimen is able to achieve a high rate of larynx preservation, a good tolerability, and a satisfactory cause-specific overall survival.

Retreatment with trastuzumab after progression on lapatinib-based therapy in heavily pretreated HER2-positive metastatic breast cancer: A single-institution experience

Aims The study aimed to determine if retreatment with trastuzumab after progression on treatment with lapatinib is feasible in a previously heavily pretreated population of HER2-positive metastatic breast cancer patients and if some range of activity and an acceptable toxicity profile could be shown. Methods and study design Women with HER2-positive metastatic breast carcinoma whose disease progressed after antracycline, taxane and trastuzumab-based regimens were treated at progression with lapatinib plus capecitabine. At progression on this combination, retreatment with trastuzumab combined with different cytotoxic agents was offered to most patients. The outcome of these patients was evaluated. Results Between April 2007 and February 2013, a total of 77 patients with HER2-positive metastatic breast cancer were identified who had been treated with lapatinib plus capecitabine at our institution. At progression, 43 (55%) were treated again with a trastuzumab-based regimen, mostly gemcitabine and vinorelbine. One complete response (CR) and 17 partial responses plus 4 prolonged stable periods longer than 6 months for a 51.1% overall clinical benefit were observed. No severe toxicities were encountered except one case of heart failure reported in a heavily antracycline-pretreated patient, who, however, recovered from this toxicity. Conclusions Even if our sample is a favorably selected population of HER2-positive patients responding to sequential targeted therapies, our data suggest that trastuzumab can be used again in association with a different cytotoxic agent in patients heavily pretreated with trastuzumab and after progression on lapatinib plus capecitabine, without any significant toxicity and with an encouraging clinical benefit rate, suggesting there is an opportunity to continue blockade of the HER2 receptor.

Abstract S3-09: Patient-reported endocrine symptoms, sexual functioning and quality of life (QoL) in the IBCSG SOFT trial: Adjuvant treatment with tamoxifen (T) alone versus tamoxifen plus ovarian function suppression (OFS) in premenopausal women with hormone receptor-po

Background: Relatively little is known about treatment-related endocrine symptoms, sexual function and QoL in premenopausal women receiving adjuvant endocrine therapy with or without OFS. SOFT is the first trial providing patient-reported data in premenopausal women undergoing OFS combined with T vs. tamoxifen alone for five years. Methods: Between Nov 2003 and Apr 2011, 3,066 premenopausal patients with HR+ BC were enrolled in the phase III trial SOFT, of whom 2,045 were randomly assigned to receive adjuvant treatment with 5 years T or T+OFS. A third group received exemestane+OFS and is not included in this report. Prior chemotherapy was allowed, provided women had confirmed premenopausal estradiol levels within 8 months of completing chemotherapy. Patients completed a questionnaire consisting of several global (physical well-being, mood, coping effort, treatment burden) and symptom-specific indicators (hot flushes, vaginal discharge, vaginal dryness, joint pain, loss of sexual interest) at baseline, every 6 months for the first 24 months, and annually years 3 to 6. Differences between the two treatments will be tested early (6 months post-randomization), mid-treatment (24 months post-randomization), and late (60 months post-randomization) using repeated measures modeling overall and by chemotherapy stratum. We anticipated women receiving T+OFS would report more endocrine symptoms and worse sexual function over the whole observation period. Results: The QoL analysis will present patient-reported outcomes including endocrine symptoms, sexual function, and global QoL domains over time. Differences between the treatments and the relative impact of endocrine symptoms on global domains will be evaluated. Current median follow-up is 5 yrs. The final analysis will be completed October 15, 2014. A separate abstract has been submitted for the efficacy analysis of this study. These results may be critical in assisting women and their doctors in weighing the risks and benefits of the two treatments. Citation Format: Karin Ribi, Weixiu Luo, Juerg Bernhard, Prudence A Francis, Meritxell Bellet, Harold J Burstein, Lorenzo Pavesi, Vani Parmar, Carlo Tondini, Marilena Visini, Roberto Torres, Per Karlsson, Simon Spazzapan, Antoni Avella, Thomas Ruhstaller, Fabio Puglisi, Meredith M Regan, Alan S Coates, Richard D Gelber, Gini F Fleming. Patient-reported endocrine symptoms, sexual functioning and quality of life (QoL) in the IBCSG SOFT trial: Adjuvant treatment with tamoxifen (T) alone versus tamoxifen plus ovarian function suppression (OFS) in premenopausal women with hormone receptor-po [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S3-09.

Abstract P1-12-06: Co-SOFT: The cognitive function substudy of the suppression of ovarian function trial (SOFT)

Background: Cognitive impairment is a potential side-effect of breast cancer (BC) treatment. Estrogen is an important neuromodulator that affects cognition. Estrogen depletion by oophorectomy or GnRH agonists may adversely affect cognition in non-oncological settings, but there are few data regarding the cognitive effects of ovarian function suppression (OFS) in women with breast cancer. Patients and Methods: Between November 2003 and January 2011, 3066 premenopausal women with hormone receptor-positive BC were randomised on the SOFT trial to 5 years of adjuvant endocrine therapy with tamoxifen alone, tamoxifen+OFS or exemestane+OFS. OFS was achieved by the GnRH agonist triptorelin, oophorectomy or ovarian irradiation. Prior chemotherapy was allowed, provided women had premenopausal estradiol levels at enrolment. Women eligible for Co-SOFT must not have received any prior adjuvant endocrine therapy. At study entry (t1), and approximately 1 year after SOFT randomisation (t2), objective cognitive function was assessed with a brief computerized test battery comprising 7 tasks (CogState Ltd: cogstate.com). Subjective cognitive function, psychological distress, fatigue, insomnia and quality of life were also assessed. Co-SOFT recruited 86 of a planned 321 patients from 27 of 426 SOFT centres between November 2007 and January 2011, when Co-SOFT was closed as the SOFT trial completed accrual. The protocol-specified primary comparison was the change in the composite score of the CogState tasks over 1 year for women randomised to tamoxifen versus tamoxifen+OFS. However, due to low accrual this was modified, prior to any analysis, to compare the tamoxifen versus the pooled tamoxifen+OFS and exemestane+OFS groups. Cognitive test scores were standardized according to age-specific norms, averaged to compute the composite score and then change between t1 and t2 calculated; a negative change in composite score indicates deterioration in cognitive function. Change in composite score was compared using Wilcoxon rank sum test. Results: Of 86 Co-SOFT enrolled patients, 74 underwent both t1 and t2 CogState testing and were included in the primary analysis (7 withdrew consent/declined assessment, 5 missed testing due to scheduling). Of these 74 women, 20 were randomised to tamoxifen and 54 to OFS+tamoxifen (28) or OFS+exemestane (26). Baseline characteristics were well balanced between the 2 groups. During the first year 49 women utilised GnRH alone for OFS, 4 had GnRH followed by oophorectomy and 1 had oophorectomy alone. There was no significant difference in the changes in the CogState composite scores from t1 and t2 for patients randomised to tamoxifen alone compared with OFS+oral endocrine therapy (median, -0.057 versus -0.146 respectively, p=0.51). There were no significant between-group differences in the changes from t1 and t2 for any of the 7 individual cognitive tasks comprising the composite score. Conclusions: The results of this 1-year longitudinal substudy suggest that the addition of OFS to oral endocrine therapy does not significantly affect cognitive function in the setting of adjuvant BC treatment. Co-SOFT was limited by small sample size, so further investigation of the impact of OFS on cognitive function in BC patients is warranted. Citation Format: Kelly-Anne Phillips, Yang Feng, Karin Ribi, Jurg Bernhard, Fabio Puglisi, Meritxell Bellet, Simon Spazzapan, Per Karlsson, Daniel R Budman, Khalil Zaman, Ehtesham A Abdi, Susan M Domchek, Meredith M Regan, Alan S Coates, Richard D Gelber, Paul Maruff, Frances Boyle, John F Forbes, Gini F Fleming, Prudence A Francis. Co-SOFT: The cognitive function substudy of the suppression of ovarian function trial (SOFT) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-06.

Abstract P5-18-05: The Promher Study: An observational Italian study on HER2+ve, pT1a-b, pN0, M0 breast cancer (BC) patients (pts)

Background. The management of small (≤ 1 cm), node-negative, HER2+ve BC is controversial, since data from randomized clinical trials specifically addressing the benefit of adjuvant systemic treatment with or without Trastuzumab in this setting are still lacking. The aims of this retrospective study are to assess how pts are managed in routinary clinical practice in Italy, whether clinical or biological features may influence the choice of adjuvant systemic therapy and if there is any difference in the outcome between treated and not treated pts. Patients and methods. Data of 268 consecutive pts who underwent surgery from January 2007 to December 2012 for HER2+ve, pT1a-b pN0 BC, were collected from 25 Italian centres. Descriptive statistical analyses and multivariate logistic regression models were used, with the aim of investigating the relationship between the baseline clinical and biological features and the adjuvant treatment strategy. Results. Pts characteristics were: median age 57, 69% postmenopausal status, 77% had conservative surgery, 32% pT1a, 68% pT1b, 48% G3, 66% ER+ve, 75% Ki67 ≥14%. Ninety percent of pts received adjuvant systemic therapy: 19% hormone therapy (HT) alone, 3% chemotherapy (CT) +/- HT, 64% Trastuzumab + CT +/- HT and 4% Trastuzumab + HT. At the multivariate analysis, the odds of being treated with adjuvant systemic therapy with or without Trastuzumab, resulted higher in presence of conservative surgery (p=0.002), pT1b (p Conclusion. This preliminary analysis shows that in Italy the majority of these pts received systemic adjuvant treatment and about 2/3 were treated with Trastuzumab. Pathological tumor size (pT1b) and negative hormone receptor status represent the main factors influencing the choice of including Trastuzumab in the adjuvant treatment. Survival data are still not mature to drive definitive conclusions about outcome. Citation Format: Stefania Gori, Monica Turazza, Simona Duranti, Elena Fiorio, Jennifer Foglietta, Marcella Gulisano, Ilaria Marcon, Marta Gubbiotti, Maria Giovanna Cavazzini, Simon Spazzapan, Valeria De Simone, Giancarlo Bisagni, Chiara Saggia, Luigi Cavanna, Emilio Bria, Laura Iezzi, Elisabetta Cretella, Patrizia Vici, Daniele Santini, Alessandra Fabi, Ornella Garrone, Antonella Ferro, Silvana Saracchini, Lucia Evangelisti, Sandro Barni, Lucia Mentuccia, Lucio Laudadio, Alessandro Inno, Gianluigi Lunardi, Francesca Coati, Luca Boni. The Promher Study: An observational Italian study on HER2+ve, pT1a-b, pN0, M0 breast cancer (BC) patients (pts) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-18-05.