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Negative PET: good prognosis for Hodgkin's lymphoma
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A significantly greater proportion of patients with untreated advanced melanoma treated with nivolumab and ipilimumab achieved an overall response than patients treated with ipilimumab alone. Both drugs are checkpoint inhibitors: ipilimumab is an anti-cytotoxic T-lymphocyte-associated antigen (CTLA)-4 antibody and nivolumab is a programmed cell death (PD)-1 inhibitor. Responses in the phase 2, double-blinded trial were especially robust in patients without BRAF mutations, of whom 61% (95% CI 49–72) in the combination group had an overall response compared with 11% (3–25) in the ipilimumab alone group. 16 (22%) patients achieved a complete response in the combination group compared with none in the ipilimumab alone group. “This trial is extremely important not just for patients but for the
whole field of immunotherapy”, said Bartosz Chmielowski, associate clinical professor of medicine at the University of California (Los Angeles, CA, USA) who was not part of the research. “The response rate of 60% for the combination is unprecedented”, he added. Trials of nivolumab or pembrolizumab (another PD-1 inhibitor) alone showed response rates of about 30% and complete responses were very infrequent, said Chmielowski. “These results, which indicate that this treatment may be used as first-line therapy, are especially important because patients without the BRAF mutation have fewer therapeutic options”, said Jedd D Wolchok, an author on the study (Memorial Sloan-Kettering Cancer Center, New York, NY, USA). The results suggest that these drugs have overlapping mechanisms of action,
both activating T cells but at different stages, he said. This trial accords with results from phase 1 trials using these two drugs, Wolchok said, adding that patients naive to the treatment had better responses than those who had previously received the treatment. This study also indicates that the ligand for PD-1 (PD-L1) does not influence response rate and is therefore not a biomarker for the combination”, said co-author F Stephen Hodi (Harvard Medical School, Boston, MA USA). The combination was generally well tolerated. However, more than half of patients had grade 3–4 toxicities, and the death of three patients was possibly due to the combined treatment, Chiemelowski said.
P Marazzi/Science Photo Library
Immunotherapy combination promising for melanomas
Published Online May 1, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70209-3 For the study by Postow and colleagues see N Engl J Med 2015; published online April 20. http:// www.nejm.org/doi/full/10.1056/ NEJMoa1414428
Vicki Brower
Negative PET: good prognosis for Hodgkin’s lymphoma Patients with early-stage Hodgkin’s lymphoma and negative PET findings after three chemotherapy cycles have a very good prognosis with or without consolidation radiotherapy, new research suggests. However, in these patients, radiotherapy—in terms of 3-year progression-free survival (PFS)—produced a 3·8% improvement. John Radford (University of Manchester, Manchester, UK) and colleagues noted that PET might help to avoid the toxic effects of radiotherapy and improve overall survival in early-stage Hodgkin’s lymphoma, by helping to decide whether a patient with this disease needs radiotherapy or no further treatment after chemotherapy. The researchers aimed to assess if patients with stage IA or stage IIA Hodgkin’s lymphoma with negative PET findings after three cycles of www.thelancet.com/oncology Vol 16 June 2015
chemotherapy (with doxorubicin, bleomycin, vinblastine, and dacarbazine) needed consolidation radiotherapy to prevent or delay disease progression. Of the 602 patients recruited, 571 underwent PET scanning after three chemotherapy cycles. Negative PET findings were noted in 426 (75%) patients. Of these patients, 420 were randomly assigned to a treatment group: 209 to the radiotherapy group and 211 to the no further treatment group. 193 (92%) patients in the radiotherapy group and 187 (89%) patients in the no further treatment group were alive during the median follow-up of 60 months. In the radiotherapy group, 3-year PFS was 94·6% (95% CI 91·5–97·7), compared with 90·8% (86·9–94·8) in the no further treatment group. For PFS, the rate ratio was 1·57 (95% CI 0·84–2·97;
p=0·16), and the 3-year absolute risk difference was −3·8% (95% CI −8·8 to 1·3). “There have been concerns for some years about the late toxicity of radiotherapy in terms of the increased risk of second cancers and cardiovascular disease”, said Radford. He stated that the study helps with “a more individualised, PET-directed approach to the treatment of earlystage Hodgkin’s lymphoma”. Anas Younes (Memorial Sloan Kettering Cancer Center, New York, NY, USA) commented, “The study provides assurances to treating oncologists and patients and their families that in selected patients with earlystage classic Hodgkin’s lymphoma, eliminating radiation therapy after three cycles of chemotherapy has little impact on treatment outcome”.
Published Online May 1, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70210-X For the study by Radford and colleagues see N Engl J Med 2015; 372: 1598–607
Sanjeet Bagcchi e265
A significantly greater proportion of patients with untreated advanced melanoma treated with nivolumab and ipilimumab achieved an overall response than patients treated with ipilimumab alone. Both drugs are checkpoint inhibitors: ipilimumab is an anti-cytotoxic T-lymphocyte-associated antigen (CTLA)-4 antibody and nivolumab is a programmed cell death (PD)-1 inhibitor. Responses in the phase 2, double-blinded trial were especially robust in patients without BRAF mutations, of whom 61% (95% CI 49–72) in the combination group had an overall response compared with 11% (3–25) in the ipilimumab alone group. 16 (22%) patients achieved a complete response in the combination group compared with none in the ipilimumab alone group. “This trial is extremely important not just for patients but for the
whole field of immunotherapy”, said Bartosz Chmielowski, associate clinical professor of medicine at the University of California (Los Angeles, CA, USA) who was not part of the research. “The response rate of 60% for the combination is unprecedented”, he added. Trials of nivolumab or pembrolizumab (another PD-1 inhibitor) alone showed response rates of about 30% and complete responses were very infrequent, said Chmielowski. “These results, which indicate that this treatment may be used as first-line therapy, are especially important because patients without the BRAF mutation have fewer therapeutic options”, said Jedd D Wolchok, an author on the study (Memorial Sloan-Kettering Cancer Center, New York, NY, USA). The results suggest that these drugs have overlapping mechanisms of action,
both activating T cells but at different stages, he said. This trial accords with results from phase 1 trials using these two drugs, Wolchok said, adding that patients naive to the treatment had better responses than those who had previously received the treatment. This study also indicates that the ligand for PD-1 (PD-L1) does not influence response rate and is therefore not a biomarker for the combination”, said co-author F Stephen Hodi (Harvard Medical School, Boston, MA USA). The combination was generally well tolerated. However, more than half of patients had grade 3–4 toxicities, and the death of three patients was possibly due to the combined treatment, Chiemelowski said.
P Marazzi/Science Photo Library
Immunotherapy combination promising for melanomas
Published Online May 1, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70209-3 For the study by Postow and colleagues see N Engl J Med 2015; published online April 20. http:// www.nejm.org/doi/full/10.1056/ NEJMoa1414428
Vicki Brower
Negative PET: good prognosis for Hodgkin’s lymphoma Patients with early-stage Hodgkin’s lymphoma and negative PET findings after three chemotherapy cycles have a very good prognosis with or without consolidation radiotherapy, new research suggests. However, in these patients, radiotherapy—in terms of 3-year progression-free survival (PFS)—produced a 3·8% improvement. John Radford (University of Manchester, Manchester, UK) and colleagues noted that PET might help to avoid the toxic effects of radiotherapy and improve overall survival in early-stage Hodgkin’s lymphoma, by helping to decide whether a patient with this disease needs radiotherapy or no further treatment after chemotherapy. The researchers aimed to assess if patients with stage IA or stage IIA Hodgkin’s lymphoma with negative PET findings after three cycles of www.thelancet.com/oncology Vol 16 June 2015
chemotherapy (with doxorubicin, bleomycin, vinblastine, and dacarbazine) needed consolidation radiotherapy to prevent or delay disease progression. Of the 602 patients recruited, 571 underwent PET scanning after three chemotherapy cycles. Negative PET findings were noted in 426 (75%) patients. Of these patients, 420 were randomly assigned to a treatment group: 209 to the radiotherapy group and 211 to the no further treatment group. 193 (92%) patients in the radiotherapy group and 187 (89%) patients in the no further treatment group were alive during the median follow-up of 60 months. In the radiotherapy group, 3-year PFS was 94·6% (95% CI 91·5–97·7), compared with 90·8% (86·9–94·8) in the no further treatment group. For PFS, the rate ratio was 1·57 (95% CI 0·84–2·97;
p=0·16), and the 3-year absolute risk difference was −3·8% (95% CI −8·8 to 1·3). “There have been concerns for some years about the late toxicity of radiotherapy in terms of the increased risk of second cancers and cardiovascular disease”, said Radford. He stated that the study helps with “a more individualised, PET-directed approach to the treatment of earlystage Hodgkin’s lymphoma”. Anas Younes (Memorial Sloan Kettering Cancer Center, New York, NY, USA) commented, “The study provides assurances to treating oncologists and patients and their families that in selected patients with earlystage classic Hodgkin’s lymphoma, eliminating radiation therapy after three cycles of chemotherapy has little impact on treatment outcome”.
Published Online May 1, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70210-X For the study by Radford and colleagues see N Engl J Med 2015; 372: 1598–607
Sanjeet Bagcchi e265