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Increases in bilateral mastectomy for breast cancer
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Patients with advanced soft-tissue sarcoma have a median overall survival of 8–12 months and a low proportion of patients achieve tumour responses after treatment with chemotherapy (30–40%). Soft-tissue sarcomas are known to have hypoxic regions which can confer resistance to chemotherapy and radiotherapy. TH-302 is a prodrug of the cytotoxic alkylating agent bromoisophosphoramide mustard; and is activated in hypoxic conditions. A phase 2 study treated 91 patients with advanced soft-tissue sarcoma with TH-302 (300 mg/m2) on days 1 and 8 of a 21-day cycle, and with doxorubicin (75 mg/m2) on day 1 of each 21-day cycle. After six treatment cycles, patients showing a tumour response could be treated with single-agent TH-302 maintenance therapy.
The authors report that the primary endpoint, 6-month progression-free survival, was 58% (95% CI 46–68) with 30 (34%) patients achieving a partial response and two (2%) patients a complete response. Median progression-free survival was 6·5 months (95% CI 5·8–7·7); median overall survival was 21·5 months (16·0–26·2). During the TH-302 maintenance phase, five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were haematological toxicities, fatigue, nausea, and skin toxicities. Progression-free survival and overall survival compare well with other first-line systemic treatments for soft-tissue sarcoma, and there is an ongoing phase 3 trial of TH-302. Bass Hassan (Oxford University, Oxford, UK) comments, “There
remains a relative lack of efficacy measurement (such as measurement of the activated metabolite) of the extent of prodrug activation to know whether it can truly add to singleagent doxorubicin in this non-curative treatment population. Progressionfree survival is not dissimilar to active agents based on progression-free survival data from EORTC, and the extent of benefit should be modelled on trials such as the PALETTE study of pazopanib in this patient population.” Ian Judson (Royal Marsden Hospital, London, UK) adds “TH-302 appears to have advantages over ifosfamide, at least in terms of side-effect profile, and the activity of the drug in combination with doxorubicin in this phase 2 study is clearly promising. We await the results of the phase 3 trial with great interest.”
Steve Gschmeissner/Science Photo Library
Hypoxia-activated TH-302 for advanced soft-tissue sarcoma
Published Online September 12, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)70447-4 For the study by Chawla and colleagues see J Clin Oncol 2014; published online Sept 2. DOI:10.1200/JCO.2013.54.3660
Ahmadur Rahman
Increases in bilateral mastectomy for breast cancer An observational cohort study has revealed sharp increases in the use of bilateral mastectomy in treating breast cancer. The researchers used a population-based cancer registry to examine surgical interventions (n=189 734) and mortality (n=174 917) for women diagnosed with stage 0–III (tumours <5 cm) breast cancer in California from 1998 to 2011. They found that the proportion of women choosing to undergo bilateral mastectomy increased from 2·0% (95% CI 1·7–2·2) to 12·3% (11·8–12·9) over the study period, a year-on-year rise of 14·3% (13·1–15·15). The investigators further noted that bilateral mastectomy conferred no survival benefit over breastconserving surgery plus radiotherapy (hazard ratio [HR] 1·02; 95% CI 0·94–1·11). Unilateral mastectomy, however, was associated with higher mortality than breast-conserving www.thelancet.com/oncology Vol 15 October 2014
surgery (HR 1·35; 95% CI 1·32–1·39). White women, those with private health insurance, and women who lived in higher socioeconomic areas were more likely to choose a bilateral mastectomy. But the researchers did not suggest that unilateral mastectomy itself is a riskier proposition for patients with breast cancer. “Patient selection attributable to unmeasured factors probably explains much of the higher mortality we observed with unilateral mastectomy relative to the other two surgical procedures”, they wrote. These factors may include unfavourable tumour characteristics and comorbidities. “Minority and lower socioeconomic status women are more likely to present with underlying health conditions that may contraindicate radiotherapy”, explained lead author Scarlett Lin
Gomez (Cancer Prevention Institute of California and Stanford School of Medicine, CA, USA). In which case, perhaps many of these women would have preferred breastconserving surgery but were advised against it. “No doctor is going to recommend bilateral mastectomy to averagerisk women”, affirmed Steven Narod (University of Toronto, Canada). He added that a bilateral mastectomy minimises the chances of a new breast cancer; it means patients are not required to return to their clinician for follow-up mammography; and it offers tremendous relief to those patients who dread the prospect of a second cancer diagnosis. “These are valid endpoints”, stresses Narod. “All three should be taken into consideration.”
Published Online September 12, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)70448-6 For the study by Kurian and colleagues see JAMA 2014; 312: 902–14
Talha Khan Burki e480
Patients with advanced soft-tissue sarcoma have a median overall survival of 8–12 months and a low proportion of patients achieve tumour responses after treatment with chemotherapy (30–40%). Soft-tissue sarcomas are known to have hypoxic regions which can confer resistance to chemotherapy and radiotherapy. TH-302 is a prodrug of the cytotoxic alkylating agent bromoisophosphoramide mustard; and is activated in hypoxic conditions. A phase 2 study treated 91 patients with advanced soft-tissue sarcoma with TH-302 (300 mg/m2) on days 1 and 8 of a 21-day cycle, and with doxorubicin (75 mg/m2) on day 1 of each 21-day cycle. After six treatment cycles, patients showing a tumour response could be treated with single-agent TH-302 maintenance therapy.
The authors report that the primary endpoint, 6-month progression-free survival, was 58% (95% CI 46–68) with 30 (34%) patients achieving a partial response and two (2%) patients a complete response. Median progression-free survival was 6·5 months (95% CI 5·8–7·7); median overall survival was 21·5 months (16·0–26·2). During the TH-302 maintenance phase, five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were haematological toxicities, fatigue, nausea, and skin toxicities. Progression-free survival and overall survival compare well with other first-line systemic treatments for soft-tissue sarcoma, and there is an ongoing phase 3 trial of TH-302. Bass Hassan (Oxford University, Oxford, UK) comments, “There
remains a relative lack of efficacy measurement (such as measurement of the activated metabolite) of the extent of prodrug activation to know whether it can truly add to singleagent doxorubicin in this non-curative treatment population. Progressionfree survival is not dissimilar to active agents based on progression-free survival data from EORTC, and the extent of benefit should be modelled on trials such as the PALETTE study of pazopanib in this patient population.” Ian Judson (Royal Marsden Hospital, London, UK) adds “TH-302 appears to have advantages over ifosfamide, at least in terms of side-effect profile, and the activity of the drug in combination with doxorubicin in this phase 2 study is clearly promising. We await the results of the phase 3 trial with great interest.”
Steve Gschmeissner/Science Photo Library
Hypoxia-activated TH-302 for advanced soft-tissue sarcoma
Published Online September 12, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)70447-4 For the study by Chawla and colleagues see J Clin Oncol 2014; published online Sept 2. DOI:10.1200/JCO.2013.54.3660
Ahmadur Rahman
Increases in bilateral mastectomy for breast cancer An observational cohort study has revealed sharp increases in the use of bilateral mastectomy in treating breast cancer. The researchers used a population-based cancer registry to examine surgical interventions (n=189 734) and mortality (n=174 917) for women diagnosed with stage 0–III (tumours <5 cm) breast cancer in California from 1998 to 2011. They found that the proportion of women choosing to undergo bilateral mastectomy increased from 2·0% (95% CI 1·7–2·2) to 12·3% (11·8–12·9) over the study period, a year-on-year rise of 14·3% (13·1–15·15). The investigators further noted that bilateral mastectomy conferred no survival benefit over breastconserving surgery plus radiotherapy (hazard ratio [HR] 1·02; 95% CI 0·94–1·11). Unilateral mastectomy, however, was associated with higher mortality than breast-conserving www.thelancet.com/oncology Vol 15 October 2014
surgery (HR 1·35; 95% CI 1·32–1·39). White women, those with private health insurance, and women who lived in higher socioeconomic areas were more likely to choose a bilateral mastectomy. But the researchers did not suggest that unilateral mastectomy itself is a riskier proposition for patients with breast cancer. “Patient selection attributable to unmeasured factors probably explains much of the higher mortality we observed with unilateral mastectomy relative to the other two surgical procedures”, they wrote. These factors may include unfavourable tumour characteristics and comorbidities. “Minority and lower socioeconomic status women are more likely to present with underlying health conditions that may contraindicate radiotherapy”, explained lead author Scarlett Lin
Gomez (Cancer Prevention Institute of California and Stanford School of Medicine, CA, USA). In which case, perhaps many of these women would have preferred breastconserving surgery but were advised against it. “No doctor is going to recommend bilateral mastectomy to averagerisk women”, affirmed Steven Narod (University of Toronto, Canada). He added that a bilateral mastectomy minimises the chances of a new breast cancer; it means patients are not required to return to their clinician for follow-up mammography; and it offers tremendous relief to those patients who dread the prospect of a second cancer diagnosis. “These are valid endpoints”, stresses Narod. “All three should be taken into consideration.”
Published Online September 12, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)70448-6 For the study by Kurian and colleagues see JAMA 2014; 312: 902–14
Talha Khan Burki e480