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Combinations of sargramostim and ipilimumab for the treatment of metastatic melanoma can extend overall survival by an average of almost 5 months compared with ipilimumab alone, latest research suggests. Previous studies have suggested that combining cytotoxic T-lymphocyteassociated antigen 4 (CTLA-4) blockade with granulocyte-macrophage colonystimulating factor (GM-CSF) secreting whole cell vaccines could have a synergistic effect against prostate cancer and ovarian carcinoma. For this latest study, Stephen Hodi and colleagues aimed to further investigate this interaction by combining ipilimumab (a fully human IgG1 monoclonal antibody that blocks CTLA-4) with sargramostim (a form of GM-CSF) to see if this had a synergistic effect against melanoma. 245 patients with unresectable stage III or IV melanoma were randomly
assigned to receive ipilimumab plus sargramostim or ipilimumab alone. Patients were followed for a median of 13·3 months. Overall, Hodi and colleagues reported that median overall survival was 17·5 months (95% CI 14·9–not reached) for patients who received combination treatment compared with 12·7 months (95% CI 10·0–not reached) for those who received ipilimumab alone. Overall survival at 1 year was 68·9% (95% CI 60·6–85·5%) for the group given the combination and 52·9% (95% CI 43·6–62·2%) for the group only given ipilimumab. Frequency of adverse events was significantly lower in the ipilimumab plus sargramostim group than in the ipilimumabonly group (p=0·04). Stephen Hodi (Dana-Farber Cancer Institute, Boston MA, USA), concluded, “This study supports the evidence that
additing sargramostim to ipilimumab treatment improved overall survival in patients with metastatic melanoma. These findings need confirmation in larger sample sizes and with longer time of follow-up.” Len Lichtenfeld (American Cancer Society, Atlanta GA, USA), said, “This is valuable research that could lead to a change in treatment approaches for patients on only ipilimumab. Addition of a second drug to boost the immune response, instead of a vaccine, is a new idea and is an area of research that will become common going forward.” Tim Turnham (Melanoma Research Foundation, Washington DC, USA), cautioned that “A true breakthrough that shows higher and durable response rates is needed before patients can feel that they are seeing significant progress”.
Steve Gschmeissner/Science Photo Library
Combination boosts survival for metastatic melanoma
Published Online November 7, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71117-9 For the study by Hodi and colleagues see JAMA 2014; 312: 1744–53
Sanjay Tanday
A nested case-control study has calculated the association between the size of the excision used to remove a cervical intraepithelial neoplasia (CIN) and the risk of preterm birth (defined as gestational age of 20–36 weeks). Women with excisions of less than 10 mm had an absolute risk of 7·5% (95% CI 6·0–8·9) of subsequently delivering a preterm baby, roughly in line with that of the general population (6·7%). But women who had larger excisions faced larger risks. For women whose excisions were longer than 20 mm, the absolute risk of a preterm birth was 18% (95% CI 10·7–25·1). Women with excisions measuring 10–14 mm had absolute risks of preterm births of 9·6% (95% CI 7·7–11·5) and 15–19 mm had a 15·3% (10·5–20·1) absolute risk. From 11 471 women, the investigators matched 1313 women who had preterm births, with the
same number of women with term births. These women were matched on study site, parity, and maternal age at delivery, and were drawn from the clinical records of 12 NHS hospitals in England. After exclusions, the cohort numbered 768 preterm births, and 830 term births. “By comparing risk in women who only had some sort of excision, we hoped that other risk factors for preterm delivery would be similar in women with a large excision and in the comparison group (women with small excisions)”, explained lead author Peter Sasieni (Queen Mary University of London, London, UK). “Since risk increased with depth of excision when carried out before pregnancy, but not if women were subsequently treated, any difference in risk is most likely due to the deep excision”. Sasieni and colleagues’ findings showed that excisions of less than
www.thelancet.com/oncology Vol 15 December 2014
10 mm are unlikely to have an effect on subsequent preterm birth. Therefore, clinicians should try to be as conservative as possible when they do the excision procedure. But, of course, they should be satisfied they have removed the entire lesion. “The whole purpose of doing the excision is to cut out the precancerous lesion—if you leave it there, in 20 years, up to half these women will have an invasive cancer”, notes Margaret Stanley (Cambridge University, Cambridge, UK). “At least now with this paper, there is very good information for clinicians to work with”. The HPV vaccination campaign will help reduce the risk of developing CIN, and therefore the need for excision. “We’re vaccinating more than 80% of girls aged 12–15 years”, said Stanley. “This should reduce these precancers by 50% in the next 15 years”.
Science Photo Library
CIN excision and preterm birth risk
Published Online November 14, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71120-9 For the study by Sasieni and colleagues see BMJ 2014; 349: g6223
Talha Khan Burki e592
Combinations of sargramostim and ipilimumab for the treatment of metastatic melanoma can extend overall survival by an average of almost 5 months compared with ipilimumab alone, latest research suggests. Previous studies have suggested that combining cytotoxic T-lymphocyteassociated antigen 4 (CTLA-4) blockade with granulocyte-macrophage colonystimulating factor (GM-CSF) secreting whole cell vaccines could have a synergistic effect against prostate cancer and ovarian carcinoma. For this latest study, Stephen Hodi and colleagues aimed to further investigate this interaction by combining ipilimumab (a fully human IgG1 monoclonal antibody that blocks CTLA-4) with sargramostim (a form of GM-CSF) to see if this had a synergistic effect against melanoma. 245 patients with unresectable stage III or IV melanoma were randomly
assigned to receive ipilimumab plus sargramostim or ipilimumab alone. Patients were followed for a median of 13·3 months. Overall, Hodi and colleagues reported that median overall survival was 17·5 months (95% CI 14·9–not reached) for patients who received combination treatment compared with 12·7 months (95% CI 10·0–not reached) for those who received ipilimumab alone. Overall survival at 1 year was 68·9% (95% CI 60·6–85·5%) for the group given the combination and 52·9% (95% CI 43·6–62·2%) for the group only given ipilimumab. Frequency of adverse events was significantly lower in the ipilimumab plus sargramostim group than in the ipilimumabonly group (p=0·04). Stephen Hodi (Dana-Farber Cancer Institute, Boston MA, USA), concluded, “This study supports the evidence that
additing sargramostim to ipilimumab treatment improved overall survival in patients with metastatic melanoma. These findings need confirmation in larger sample sizes and with longer time of follow-up.” Len Lichtenfeld (American Cancer Society, Atlanta GA, USA), said, “This is valuable research that could lead to a change in treatment approaches for patients on only ipilimumab. Addition of a second drug to boost the immune response, instead of a vaccine, is a new idea and is an area of research that will become common going forward.” Tim Turnham (Melanoma Research Foundation, Washington DC, USA), cautioned that “A true breakthrough that shows higher and durable response rates is needed before patients can feel that they are seeing significant progress”.
Steve Gschmeissner/Science Photo Library
Combination boosts survival for metastatic melanoma
Published Online November 7, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71117-9 For the study by Hodi and colleagues see JAMA 2014; 312: 1744–53
Sanjay Tanday
A nested case-control study has calculated the association between the size of the excision used to remove a cervical intraepithelial neoplasia (CIN) and the risk of preterm birth (defined as gestational age of 20–36 weeks). Women with excisions of less than 10 mm had an absolute risk of 7·5% (95% CI 6·0–8·9) of subsequently delivering a preterm baby, roughly in line with that of the general population (6·7%). But women who had larger excisions faced larger risks. For women whose excisions were longer than 20 mm, the absolute risk of a preterm birth was 18% (95% CI 10·7–25·1). Women with excisions measuring 10–14 mm had absolute risks of preterm births of 9·6% (95% CI 7·7–11·5) and 15–19 mm had a 15·3% (10·5–20·1) absolute risk. From 11 471 women, the investigators matched 1313 women who had preterm births, with the
same number of women with term births. These women were matched on study site, parity, and maternal age at delivery, and were drawn from the clinical records of 12 NHS hospitals in England. After exclusions, the cohort numbered 768 preterm births, and 830 term births. “By comparing risk in women who only had some sort of excision, we hoped that other risk factors for preterm delivery would be similar in women with a large excision and in the comparison group (women with small excisions)”, explained lead author Peter Sasieni (Queen Mary University of London, London, UK). “Since risk increased with depth of excision when carried out before pregnancy, but not if women were subsequently treated, any difference in risk is most likely due to the deep excision”. Sasieni and colleagues’ findings showed that excisions of less than
www.thelancet.com/oncology Vol 15 December 2014
10 mm are unlikely to have an effect on subsequent preterm birth. Therefore, clinicians should try to be as conservative as possible when they do the excision procedure. But, of course, they should be satisfied they have removed the entire lesion. “The whole purpose of doing the excision is to cut out the precancerous lesion—if you leave it there, in 20 years, up to half these women will have an invasive cancer”, notes Margaret Stanley (Cambridge University, Cambridge, UK). “At least now with this paper, there is very good information for clinicians to work with”. The HPV vaccination campaign will help reduce the risk of developing CIN, and therefore the need for excision. “We’re vaccinating more than 80% of girls aged 12–15 years”, said Stanley. “This should reduce these precancers by 50% in the next 15 years”.
Science Photo Library
CIN excision and preterm birth risk
Published Online November 14, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71120-9 For the study by Sasieni and colleagues see BMJ 2014; 349: g6223
Talha Khan Burki e592
