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Aromatase inhibitors may reduce endometrial cancer risk
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Use of aromatase inhibitors, which are known to reduce endogenous oestrogen levels, as adjuvant therapy had a lower risk of endometrial cancer, compared with that of patients who were treated with tamoxifen, results of a new study show. In this study, Rowan Chleblowski and colleagues (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, CA, USA) examined the records of 17 064 patients over 21 (2·7–9·0) years who were members of a community-based health plan. 148 (0·87%) patients developed endometrial cancer during the study. All patients were post-menopausal and had hormone-positive breast cancer. In the subset of 14 245 patients exposed to the endocrine treatments, the incidence of endometrial cancer was 48% lower in patients treated with the aromatase inhibitor only,
compared with the tamoxifen group (hazard ratio 0·52, 95% CI, 0·31–0·87, p=0·01). “These results are reassuring, as they come from a real-world setting”, says Clifford Hudis (Memorial Sloan-Kettering Cancer Center, New York, NY, USA). “On the biological front, we might predict that aromatase inhibitors would not cause endometrial cancer as they lower oestrogen levels below baseline. Tamoxifen’s effects are more complicated, with oestrogenblocking effects in the breast, but oestrogen-like effects in the uterus, which causes hyperplasia”, Hudis adds. For this reason, aromatase inhibitors are through to be more effective in reducing oestrogen levels than is tamoxifen. The results of this trial confirm and expand results from four previous trials, that endometrial cancer risk is greater in women with higher
endogenous levels of oestrogen, Chlebowski continues, adding that the implications of this trial might extend beyond the breast cancer population. “An intervention that can lower the risk of both breast and endometrial cancer in post-menopausal women, a third of whom are obese and therefore at higher risk for both cancers, could make a significant impact as a chemoprevention. The post-menopausal, obese population is already at risk for breast and endometrial cancers”, Chlebowski comments. Hudis recommends that although aromatase inhibitors are superior to tamoxifen in reducing risk of endometrial cancer, the risk–benefit ratio and effects on quality of life of both drugs must be assessed in individual cases.
Tim Evans/SPL
Aromatase inhibitors may reduce endometrial cancer risk
Published Online March 20, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70119-1 For the study by Chlebowski and colleagues see Cancer 2015; published online March 10. DOI:10.1002/cncr.29332
Vicki Brower
Sunitinib benefits patients with small-cell lung cancer Sunitinib, a tyrosine kinase inhibitor, after chemotherapy is safe and improves progression-free survival in patients with extensive-stage smallcell lung cancer, US study results show. Although chemotherapy is known to induce response rates of up to 80% and improve survival, many patients with small-cell lung cancer often relapse within 6 months of first-line chemotherapy. To improve outcomes, Neal Ready and colleagues (Duke University Medical Centre, Durham, NC, USA) assessed the efficacy of maintenance sunitinib, which inhibits several targets of interest in small-cell lung cancer, such as VEGF receptors, after chemotherapy for small-cell lung cancer. In this phase 2 study, 41 patients received a placebo and 44 patients received sunitinib (37·5 mg daily) until disease progression. www.thelancet.com/oncology Vol 16 April 2015
Overall, the researchers found that for the patients who received maintenance sunitinib therapy, median progression-free survival was 3·7 months (95% CI 1·8–4·3, compared with 2·1 months (95% CI 1·6–2·6) for the placebo group (hazard ratio 1·62, 95% CI 1·02–2·60, onesided p=0·02). The median overall survival was 6·9 months (95% CI 5·4–11·8) in the placebo group and 9·0 months (95% CI 8·0–12·7) in the sunitinib group (hazard ratio 1·28, 95% CI 0·79–2·10, one-sided p=0·16). No major adverse events were recorded in the 44 patients who received maintenance sunitinib. The most common side-effects were fatigue, neutropenia, leucopenia, and thrombocytopenia. “There has been no new systemic therapy for small-cell lung cancer in
20 years. This study shows activity for sunitinib, and potentially other agents in this class, for patients with small-cell lung cancer. Some individuals in the study achieved a complete response on maintenance sunitinib. We need to build on this with future studies that look at biomarkers that could identify the patients who may benefit most from sunitinib”, says Ready. According to Siow Ming Lee (Cancer Research UK and University College London, London, UK), “other drugs for small-cell lung cancer have showed results in phase 2 but failed to confirm findings in phase 3. This is a small phase 2 screening study and needs to go through further clinical trials before any recommendations are made for treatment.”
Published Online March 20, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70120-8 For the study by Ready and colleagues see J Clin Oncol 2015; published online March 2. DOI:10.1200/JCO.2014.57.3105
Sanjay Tanday e164
Use of aromatase inhibitors, which are known to reduce endogenous oestrogen levels, as adjuvant therapy had a lower risk of endometrial cancer, compared with that of patients who were treated with tamoxifen, results of a new study show. In this study, Rowan Chleblowski and colleagues (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, CA, USA) examined the records of 17 064 patients over 21 (2·7–9·0) years who were members of a community-based health plan. 148 (0·87%) patients developed endometrial cancer during the study. All patients were post-menopausal and had hormone-positive breast cancer. In the subset of 14 245 patients exposed to the endocrine treatments, the incidence of endometrial cancer was 48% lower in patients treated with the aromatase inhibitor only,
compared with the tamoxifen group (hazard ratio 0·52, 95% CI, 0·31–0·87, p=0·01). “These results are reassuring, as they come from a real-world setting”, says Clifford Hudis (Memorial Sloan-Kettering Cancer Center, New York, NY, USA). “On the biological front, we might predict that aromatase inhibitors would not cause endometrial cancer as they lower oestrogen levels below baseline. Tamoxifen’s effects are more complicated, with oestrogenblocking effects in the breast, but oestrogen-like effects in the uterus, which causes hyperplasia”, Hudis adds. For this reason, aromatase inhibitors are through to be more effective in reducing oestrogen levels than is tamoxifen. The results of this trial confirm and expand results from four previous trials, that endometrial cancer risk is greater in women with higher
endogenous levels of oestrogen, Chlebowski continues, adding that the implications of this trial might extend beyond the breast cancer population. “An intervention that can lower the risk of both breast and endometrial cancer in post-menopausal women, a third of whom are obese and therefore at higher risk for both cancers, could make a significant impact as a chemoprevention. The post-menopausal, obese population is already at risk for breast and endometrial cancers”, Chlebowski comments. Hudis recommends that although aromatase inhibitors are superior to tamoxifen in reducing risk of endometrial cancer, the risk–benefit ratio and effects on quality of life of both drugs must be assessed in individual cases.
Tim Evans/SPL
Aromatase inhibitors may reduce endometrial cancer risk
Published Online March 20, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70119-1 For the study by Chlebowski and colleagues see Cancer 2015; published online March 10. DOI:10.1002/cncr.29332
Vicki Brower
Sunitinib benefits patients with small-cell lung cancer Sunitinib, a tyrosine kinase inhibitor, after chemotherapy is safe and improves progression-free survival in patients with extensive-stage smallcell lung cancer, US study results show. Although chemotherapy is known to induce response rates of up to 80% and improve survival, many patients with small-cell lung cancer often relapse within 6 months of first-line chemotherapy. To improve outcomes, Neal Ready and colleagues (Duke University Medical Centre, Durham, NC, USA) assessed the efficacy of maintenance sunitinib, which inhibits several targets of interest in small-cell lung cancer, such as VEGF receptors, after chemotherapy for small-cell lung cancer. In this phase 2 study, 41 patients received a placebo and 44 patients received sunitinib (37·5 mg daily) until disease progression. www.thelancet.com/oncology Vol 16 April 2015
Overall, the researchers found that for the patients who received maintenance sunitinib therapy, median progression-free survival was 3·7 months (95% CI 1·8–4·3, compared with 2·1 months (95% CI 1·6–2·6) for the placebo group (hazard ratio 1·62, 95% CI 1·02–2·60, onesided p=0·02). The median overall survival was 6·9 months (95% CI 5·4–11·8) in the placebo group and 9·0 months (95% CI 8·0–12·7) in the sunitinib group (hazard ratio 1·28, 95% CI 0·79–2·10, one-sided p=0·16). No major adverse events were recorded in the 44 patients who received maintenance sunitinib. The most common side-effects were fatigue, neutropenia, leucopenia, and thrombocytopenia. “There has been no new systemic therapy for small-cell lung cancer in
20 years. This study shows activity for sunitinib, and potentially other agents in this class, for patients with small-cell lung cancer. Some individuals in the study achieved a complete response on maintenance sunitinib. We need to build on this with future studies that look at biomarkers that could identify the patients who may benefit most from sunitinib”, says Ready. According to Siow Ming Lee (Cancer Research UK and University College London, London, UK), “other drugs for small-cell lung cancer have showed results in phase 2 but failed to confirm findings in phase 3. This is a small phase 2 screening study and needs to go through further clinical trials before any recommendations are made for treatment.”
Published Online March 20, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70120-8 For the study by Ready and colleagues see J Clin Oncol 2015; published online March 2. DOI:10.1200/JCO.2014.57.3105
Sanjay Tanday e164