User login
New neoadjuvant regimen for locally advanced rectal cancer is efficacious
A new sequential neoadjuvant regimen using short-course radiation offers a similarly effective and more convenient treatment option for locally advanced rectal cancer when compared with standard chemoradiation, finds a randomized phase III trial being reported at the Gastrointestinal Cancers Symposium.
The trial, known as Polish II, was conducted among 515 patients from centers throughout Poland who had stage cT4 or fixed cT3 disease but no distant metastases.
Those in the investigational arm received a short course of radiation therapy lasting just 5 days, followed by three cycles of FOLFOX-4 chemotherapy given over 6 weeks. Those in the control arm received chemoradiation consisting of 5.5 weeks of radiation with fluorouracil, leucovorin, and oxaliplatin. After a rest, all patients underwent surgery at 12 weeks from the start of treatment.
The trial failed to meet its primary endpoint of a significantly higher rate of radical resection with the new regimen vs. chemoradiation, according to data reported in a presscast held before the symposium. However, it did find a lower rate of acute toxicity and, with 35 months of follow-up, an absolute 8% improvement in the 3-year rate of overall survival.
“Despite the fact that the trial was negative ... we show for the first time an alternative to the standard chemoradiation lasting for 5 and a half weeks,” said study coauthor Dr. Lucjan Wyrwicz, head of the Medical Oncology Unit in the Department of Gastrointestinal Cancer at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.
The new regimen may be preferable in some clinical scenarios, he noted. For example, the short course of radiation may appeal to patients who want to minimize time off from work, and it may be advantageous when cost or lack of insurance is an issue, and in low-resource countries where there are not enough radiation therapy facilities to go around.
Additionally, the regimen is a more attractive option in patients who have metastases, as they can get some full chemotherapy upfront. In contrast, with chemoradiation, it is typically delayed until several weeks after surgery, essentially leaving metastases uncontrolled in the meantime.
“Having two standards is better than having one standard. We need to try to personalize medicine,” Dr. Wyrwicz summarized.
A caveat to the trial was the use of oxaliplatin, which was included in the protocol before other trials showed that it did not improve outcomes but did add toxicity, he noted. The protocol was amended partway through to allow its omission, but about two-thirds of patients in both arms received the drug. However, findings were much the same whether patients received oxaliplatin or not, he said ahead of the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
ASCO expert and presscast moderator Dr. Smitha Krishnamurthi commented, “This is a randomized comparison of short-course radiation with chemotherapy that is demonstrating equal efficacy to traditional chemoradiation. Giving patients a shorter, more convenient, less expensive radiation, and moving the chemotherapy (some of it) upfront appears to be equally active to the chemoradiation. So it does give patients another choice.”
The finding of a lower rate of acute toxicity with the new regimen should be viewed with caution, given the use of oxaliplatin in chemoradiation, which would not be done today, she said.
Uptake of short-course radiation has been greater in Europe than in the United States, according to Dr. Krishnamurthi of Case Western Reserve University, Cleveland. This is possibly because of data from an earlier trial by the Trans Tasman Radiation Oncology Group showing a nonsignificantly higher rate of local recurrence with the short course in patients with less advanced disease.
“There are some other randomized trials which are ongoing, so there’s a lot of interest in this short-course radiation. And I think when we have all of this data together, we will be in a much better position to incorporate it,” she concluded.
In the Polish II trial, the rate of radical (R0) resection did not differ significantly between the new short-course regimen and chemoradiation, although there was a trend favoring the former (77% vs. 71%; P = .081), Dr. Wyrwicz reported.
Patients given the new regimen were less likely to experience acute toxicities (75% vs. 83%; P = .006) but not specifically grade 3 and 4 toxicities. The rate of pathologic complete response did not differ significantly.
The 3-year overall survival rate was higher with the new short-course regimen (73% vs. 65%; P = .046). The groups did not differ significantly with respect to disease-free survival or the incidences of local failure and distant metastases.
A new sequential neoadjuvant regimen using short-course radiation offers a similarly effective and more convenient treatment option for locally advanced rectal cancer when compared with standard chemoradiation, finds a randomized phase III trial being reported at the Gastrointestinal Cancers Symposium.
The trial, known as Polish II, was conducted among 515 patients from centers throughout Poland who had stage cT4 or fixed cT3 disease but no distant metastases.
Those in the investigational arm received a short course of radiation therapy lasting just 5 days, followed by three cycles of FOLFOX-4 chemotherapy given over 6 weeks. Those in the control arm received chemoradiation consisting of 5.5 weeks of radiation with fluorouracil, leucovorin, and oxaliplatin. After a rest, all patients underwent surgery at 12 weeks from the start of treatment.
The trial failed to meet its primary endpoint of a significantly higher rate of radical resection with the new regimen vs. chemoradiation, according to data reported in a presscast held before the symposium. However, it did find a lower rate of acute toxicity and, with 35 months of follow-up, an absolute 8% improvement in the 3-year rate of overall survival.
“Despite the fact that the trial was negative ... we show for the first time an alternative to the standard chemoradiation lasting for 5 and a half weeks,” said study coauthor Dr. Lucjan Wyrwicz, head of the Medical Oncology Unit in the Department of Gastrointestinal Cancer at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.
The new regimen may be preferable in some clinical scenarios, he noted. For example, the short course of radiation may appeal to patients who want to minimize time off from work, and it may be advantageous when cost or lack of insurance is an issue, and in low-resource countries where there are not enough radiation therapy facilities to go around.
Additionally, the regimen is a more attractive option in patients who have metastases, as they can get some full chemotherapy upfront. In contrast, with chemoradiation, it is typically delayed until several weeks after surgery, essentially leaving metastases uncontrolled in the meantime.
“Having two standards is better than having one standard. We need to try to personalize medicine,” Dr. Wyrwicz summarized.
A caveat to the trial was the use of oxaliplatin, which was included in the protocol before other trials showed that it did not improve outcomes but did add toxicity, he noted. The protocol was amended partway through to allow its omission, but about two-thirds of patients in both arms received the drug. However, findings were much the same whether patients received oxaliplatin or not, he said ahead of the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
ASCO expert and presscast moderator Dr. Smitha Krishnamurthi commented, “This is a randomized comparison of short-course radiation with chemotherapy that is demonstrating equal efficacy to traditional chemoradiation. Giving patients a shorter, more convenient, less expensive radiation, and moving the chemotherapy (some of it) upfront appears to be equally active to the chemoradiation. So it does give patients another choice.”
The finding of a lower rate of acute toxicity with the new regimen should be viewed with caution, given the use of oxaliplatin in chemoradiation, which would not be done today, she said.
Uptake of short-course radiation has been greater in Europe than in the United States, according to Dr. Krishnamurthi of Case Western Reserve University, Cleveland. This is possibly because of data from an earlier trial by the Trans Tasman Radiation Oncology Group showing a nonsignificantly higher rate of local recurrence with the short course in patients with less advanced disease.
“There are some other randomized trials which are ongoing, so there’s a lot of interest in this short-course radiation. And I think when we have all of this data together, we will be in a much better position to incorporate it,” she concluded.
In the Polish II trial, the rate of radical (R0) resection did not differ significantly between the new short-course regimen and chemoradiation, although there was a trend favoring the former (77% vs. 71%; P = .081), Dr. Wyrwicz reported.
Patients given the new regimen were less likely to experience acute toxicities (75% vs. 83%; P = .006) but not specifically grade 3 and 4 toxicities. The rate of pathologic complete response did not differ significantly.
The 3-year overall survival rate was higher with the new short-course regimen (73% vs. 65%; P = .046). The groups did not differ significantly with respect to disease-free survival or the incidences of local failure and distant metastases.
A new sequential neoadjuvant regimen using short-course radiation offers a similarly effective and more convenient treatment option for locally advanced rectal cancer when compared with standard chemoradiation, finds a randomized phase III trial being reported at the Gastrointestinal Cancers Symposium.
The trial, known as Polish II, was conducted among 515 patients from centers throughout Poland who had stage cT4 or fixed cT3 disease but no distant metastases.
Those in the investigational arm received a short course of radiation therapy lasting just 5 days, followed by three cycles of FOLFOX-4 chemotherapy given over 6 weeks. Those in the control arm received chemoradiation consisting of 5.5 weeks of radiation with fluorouracil, leucovorin, and oxaliplatin. After a rest, all patients underwent surgery at 12 weeks from the start of treatment.
The trial failed to meet its primary endpoint of a significantly higher rate of radical resection with the new regimen vs. chemoradiation, according to data reported in a presscast held before the symposium. However, it did find a lower rate of acute toxicity and, with 35 months of follow-up, an absolute 8% improvement in the 3-year rate of overall survival.
“Despite the fact that the trial was negative ... we show for the first time an alternative to the standard chemoradiation lasting for 5 and a half weeks,” said study coauthor Dr. Lucjan Wyrwicz, head of the Medical Oncology Unit in the Department of Gastrointestinal Cancer at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.
The new regimen may be preferable in some clinical scenarios, he noted. For example, the short course of radiation may appeal to patients who want to minimize time off from work, and it may be advantageous when cost or lack of insurance is an issue, and in low-resource countries where there are not enough radiation therapy facilities to go around.
Additionally, the regimen is a more attractive option in patients who have metastases, as they can get some full chemotherapy upfront. In contrast, with chemoradiation, it is typically delayed until several weeks after surgery, essentially leaving metastases uncontrolled in the meantime.
“Having two standards is better than having one standard. We need to try to personalize medicine,” Dr. Wyrwicz summarized.
A caveat to the trial was the use of oxaliplatin, which was included in the protocol before other trials showed that it did not improve outcomes but did add toxicity, he noted. The protocol was amended partway through to allow its omission, but about two-thirds of patients in both arms received the drug. However, findings were much the same whether patients received oxaliplatin or not, he said ahead of the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
ASCO expert and presscast moderator Dr. Smitha Krishnamurthi commented, “This is a randomized comparison of short-course radiation with chemotherapy that is demonstrating equal efficacy to traditional chemoradiation. Giving patients a shorter, more convenient, less expensive radiation, and moving the chemotherapy (some of it) upfront appears to be equally active to the chemoradiation. So it does give patients another choice.”
The finding of a lower rate of acute toxicity with the new regimen should be viewed with caution, given the use of oxaliplatin in chemoradiation, which would not be done today, she said.
Uptake of short-course radiation has been greater in Europe than in the United States, according to Dr. Krishnamurthi of Case Western Reserve University, Cleveland. This is possibly because of data from an earlier trial by the Trans Tasman Radiation Oncology Group showing a nonsignificantly higher rate of local recurrence with the short course in patients with less advanced disease.
“There are some other randomized trials which are ongoing, so there’s a lot of interest in this short-course radiation. And I think when we have all of this data together, we will be in a much better position to incorporate it,” she concluded.
In the Polish II trial, the rate of radical (R0) resection did not differ significantly between the new short-course regimen and chemoradiation, although there was a trend favoring the former (77% vs. 71%; P = .081), Dr. Wyrwicz reported.
Patients given the new regimen were less likely to experience acute toxicities (75% vs. 83%; P = .006) but not specifically grade 3 and 4 toxicities. The rate of pathologic complete response did not differ significantly.
The 3-year overall survival rate was higher with the new short-course regimen (73% vs. 65%; P = .046). The groups did not differ significantly with respect to disease-free survival or the incidences of local failure and distant metastases.
FROM THE GASTROINTESTINAL CANCERS SYMPOSIUM
Key clinical point: A regimen of short-course radiation followed by chemotherapy offers a new treatment option for patients with locally advanced rectal cancer.
Major finding: Compared with chemoradiation, the new regimen did not significantly improve local disease outcomes but did yield a significantly better 3-year overall survival rate (73% vs. 65%).
Data source: A randomized phase III trial among 515 patients with locally advanced rectal cancer (Polish II trial).
Disclosures: Dr. Wyrwicz disclosed that he had no relevant conflicts of interest. The study received funding from the Polish Ministry of Science and Higher Education.
Everolimus is effective across diverse patients with GI neuroendocrine tumors
Everolimus improves outcomes in patients with advanced, progressive neuroendocrine tumors of gastrointestinal (GI) or unknown origin regardless of primary location and prior therapy, according to new subgroup analyses of the RADIANT-4 trial.
The phase III trial is the largest of its type in patients with nonfunctioning GI tract or lung neuroendocrine tumors. The subgroup findings for those whose tumors originated in the GI tract or an unknown site (but suspected to be GI) were presented in a presscast held in advance of the Gastrointestinal Cancers Symposium.
Compared with placebo, everolimus prolonged progression-free survival by 6-9 months, corresponding to a 46%-48% relative reduction in the risk of progression or death, reported lead study author Dr. Simron Singh of Sunnybrook’s Odette Cancer Centre in Toronto. Benefit was similar regardless of whether patients had midgut or non-midgut tumors, and whether they had previously received a somatostatin analog or not.
“In my opinion, this study in advanced, progressive neuroendocrine patients [shows] an effective, new and exciting treatment option in a disease where we’ve had very few treatments to date,” Dr. Singh said ahead of the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
ASCO expert and presscast moderator Dr. Smitha Krishnamurthi of Case Western Reserve University, Cleveland, agreed, saying that everolimus could help address an unmet need in this disease.
“Patients with GI neuroendocrine tumors have had very few treatment options. Once they have progressed on somatostatin analogues, there really are no good systemic treatments,” she said. “So this finding is very important, that the mTOR inhibitor everolimus has demonstrated an improvement in risk of progression by over 40% and with very little severe toxicity. This is a welcome finding for these patients who have limited systemic treatment options.”
Patients enrolled in RADIANT-4 had lung, GI, or unknown-origin neuroendocrine tumors that had progressed on other therapies, including somatostatin analogs, surgery, or chemotherapy.
They were randomly assigned in 2:1 ratio to receive everolimus (Afinitor) or placebo, each in addition to best supportive care. Everolimus is currently approved by the Food and Drug Administration for the treatment of pancreatic neuroendocrine tumors, as well as breast and kidney cancer, and subependymal giant cell astrocytoma.
Results for the entire trial population have been previously reported and showed that everolimus prolonged progression-free survival by 7.1 months, reducing the risk of events by 52% (Lancet. 2015 Dec 15. doi.org/10.1016/S0140-6736[15]01234-9).
The new subgroup analyses were restricted to the patients with tumors originating in the GI tract (n =175) or an unknown site generally thought to be the GI tract (n = 36).
Among the group with GI tumors, median progression-free survival was 13.1 months with everolimus versus 5.4 months with placebo, Dr. Singh reported. Among the group with tumors of unknown origin, it was 13.6 and 7.5 months, respectively.
Relative to placebo, everolimus prolonged progression-free survival by 6.41 months, reducing the risk of events by 29%, in patients whose tumors originated in the midgut (duodenum, ileum, jejunum, cecum, or appendix). The relative benefit was 6.17 months, with a reduction in the risk of events of 73%, in patients whose tumors originated in non-midgut sites (stomach, colon, and rectum).
In addition, everolimus prolonged progression-free survival by 6.73 months, reducing the risk of events by 46%, in patients who had previously received somatostatin analogues, and by 9.07 months, reducing the risk by 48%, in patients who had not received these agents.
The safety profile of everolimus was consistent with that expected based on the use of this agent in other patient populations, according to Dr. Singh. The most common adverse events were stomatitis, infections, diarrhea, peripheral edema, and fatigue. No new safety signals were seen.
Dr. Singh disclosed that he receives honoraria from, has a consulting or advisory role with, and receives research funding (institutional) and travel, accommodations, and expenses from Novartis. The study received funding from Novartis Pharmaceuticals.
Everolimus improves outcomes in patients with advanced, progressive neuroendocrine tumors of gastrointestinal (GI) or unknown origin regardless of primary location and prior therapy, according to new subgroup analyses of the RADIANT-4 trial.
The phase III trial is the largest of its type in patients with nonfunctioning GI tract or lung neuroendocrine tumors. The subgroup findings for those whose tumors originated in the GI tract or an unknown site (but suspected to be GI) were presented in a presscast held in advance of the Gastrointestinal Cancers Symposium.
Compared with placebo, everolimus prolonged progression-free survival by 6-9 months, corresponding to a 46%-48% relative reduction in the risk of progression or death, reported lead study author Dr. Simron Singh of Sunnybrook’s Odette Cancer Centre in Toronto. Benefit was similar regardless of whether patients had midgut or non-midgut tumors, and whether they had previously received a somatostatin analog or not.
“In my opinion, this study in advanced, progressive neuroendocrine patients [shows] an effective, new and exciting treatment option in a disease where we’ve had very few treatments to date,” Dr. Singh said ahead of the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
ASCO expert and presscast moderator Dr. Smitha Krishnamurthi of Case Western Reserve University, Cleveland, agreed, saying that everolimus could help address an unmet need in this disease.
“Patients with GI neuroendocrine tumors have had very few treatment options. Once they have progressed on somatostatin analogues, there really are no good systemic treatments,” she said. “So this finding is very important, that the mTOR inhibitor everolimus has demonstrated an improvement in risk of progression by over 40% and with very little severe toxicity. This is a welcome finding for these patients who have limited systemic treatment options.”
Patients enrolled in RADIANT-4 had lung, GI, or unknown-origin neuroendocrine tumors that had progressed on other therapies, including somatostatin analogs, surgery, or chemotherapy.
They were randomly assigned in 2:1 ratio to receive everolimus (Afinitor) or placebo, each in addition to best supportive care. Everolimus is currently approved by the Food and Drug Administration for the treatment of pancreatic neuroendocrine tumors, as well as breast and kidney cancer, and subependymal giant cell astrocytoma.
Results for the entire trial population have been previously reported and showed that everolimus prolonged progression-free survival by 7.1 months, reducing the risk of events by 52% (Lancet. 2015 Dec 15. doi.org/10.1016/S0140-6736[15]01234-9).
The new subgroup analyses were restricted to the patients with tumors originating in the GI tract (n =175) or an unknown site generally thought to be the GI tract (n = 36).
Among the group with GI tumors, median progression-free survival was 13.1 months with everolimus versus 5.4 months with placebo, Dr. Singh reported. Among the group with tumors of unknown origin, it was 13.6 and 7.5 months, respectively.
Relative to placebo, everolimus prolonged progression-free survival by 6.41 months, reducing the risk of events by 29%, in patients whose tumors originated in the midgut (duodenum, ileum, jejunum, cecum, or appendix). The relative benefit was 6.17 months, with a reduction in the risk of events of 73%, in patients whose tumors originated in non-midgut sites (stomach, colon, and rectum).
In addition, everolimus prolonged progression-free survival by 6.73 months, reducing the risk of events by 46%, in patients who had previously received somatostatin analogues, and by 9.07 months, reducing the risk by 48%, in patients who had not received these agents.
The safety profile of everolimus was consistent with that expected based on the use of this agent in other patient populations, according to Dr. Singh. The most common adverse events were stomatitis, infections, diarrhea, peripheral edema, and fatigue. No new safety signals were seen.
Dr. Singh disclosed that he receives honoraria from, has a consulting or advisory role with, and receives research funding (institutional) and travel, accommodations, and expenses from Novartis. The study received funding from Novartis Pharmaceuticals.
Everolimus improves outcomes in patients with advanced, progressive neuroendocrine tumors of gastrointestinal (GI) or unknown origin regardless of primary location and prior therapy, according to new subgroup analyses of the RADIANT-4 trial.
The phase III trial is the largest of its type in patients with nonfunctioning GI tract or lung neuroendocrine tumors. The subgroup findings for those whose tumors originated in the GI tract or an unknown site (but suspected to be GI) were presented in a presscast held in advance of the Gastrointestinal Cancers Symposium.
Compared with placebo, everolimus prolonged progression-free survival by 6-9 months, corresponding to a 46%-48% relative reduction in the risk of progression or death, reported lead study author Dr. Simron Singh of Sunnybrook’s Odette Cancer Centre in Toronto. Benefit was similar regardless of whether patients had midgut or non-midgut tumors, and whether they had previously received a somatostatin analog or not.
“In my opinion, this study in advanced, progressive neuroendocrine patients [shows] an effective, new and exciting treatment option in a disease where we’ve had very few treatments to date,” Dr. Singh said ahead of the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
ASCO expert and presscast moderator Dr. Smitha Krishnamurthi of Case Western Reserve University, Cleveland, agreed, saying that everolimus could help address an unmet need in this disease.
“Patients with GI neuroendocrine tumors have had very few treatment options. Once they have progressed on somatostatin analogues, there really are no good systemic treatments,” she said. “So this finding is very important, that the mTOR inhibitor everolimus has demonstrated an improvement in risk of progression by over 40% and with very little severe toxicity. This is a welcome finding for these patients who have limited systemic treatment options.”
Patients enrolled in RADIANT-4 had lung, GI, or unknown-origin neuroendocrine tumors that had progressed on other therapies, including somatostatin analogs, surgery, or chemotherapy.
They were randomly assigned in 2:1 ratio to receive everolimus (Afinitor) or placebo, each in addition to best supportive care. Everolimus is currently approved by the Food and Drug Administration for the treatment of pancreatic neuroendocrine tumors, as well as breast and kidney cancer, and subependymal giant cell astrocytoma.
Results for the entire trial population have been previously reported and showed that everolimus prolonged progression-free survival by 7.1 months, reducing the risk of events by 52% (Lancet. 2015 Dec 15. doi.org/10.1016/S0140-6736[15]01234-9).
The new subgroup analyses were restricted to the patients with tumors originating in the GI tract (n =175) or an unknown site generally thought to be the GI tract (n = 36).
Among the group with GI tumors, median progression-free survival was 13.1 months with everolimus versus 5.4 months with placebo, Dr. Singh reported. Among the group with tumors of unknown origin, it was 13.6 and 7.5 months, respectively.
Relative to placebo, everolimus prolonged progression-free survival by 6.41 months, reducing the risk of events by 29%, in patients whose tumors originated in the midgut (duodenum, ileum, jejunum, cecum, or appendix). The relative benefit was 6.17 months, with a reduction in the risk of events of 73%, in patients whose tumors originated in non-midgut sites (stomach, colon, and rectum).
In addition, everolimus prolonged progression-free survival by 6.73 months, reducing the risk of events by 46%, in patients who had previously received somatostatin analogues, and by 9.07 months, reducing the risk by 48%, in patients who had not received these agents.
The safety profile of everolimus was consistent with that expected based on the use of this agent in other patient populations, according to Dr. Singh. The most common adverse events were stomatitis, infections, diarrhea, peripheral edema, and fatigue. No new safety signals were seen.
Dr. Singh disclosed that he receives honoraria from, has a consulting or advisory role with, and receives research funding (institutional) and travel, accommodations, and expenses from Novartis. The study received funding from Novartis Pharmaceuticals.
FROM THE GASTROINTESTINAL CANCERS SYMPOSIUM
Key clinical point: Everolimus reduces the risk of progression or death across subgroups of patients who have advanced, progressive neuroendocrine tumors arising in the GI tract or an unknown site.
Major finding: Compared with placebo, everolimus prolonged median progression-free survival by 6-9 months in patients with midgut and non-midgut tumors, and in patients who had and had not received somatostatin analogues.
Data source: A subgroups analysis of a phase III trial among 211 patients with advanced, progressive nonfunctioning neuroendocrine tumors originating in the GI tract or an unknown site (RADIANT-4 trial).
Disclosures: Dr. Singh disclosed that he receives honoraria from, has a consulting or advisory role with, and receives research funding (institutional) and travel, accommodations, and expenses from Novartis. The study received funding from Novartis Pharmaceuticals.
Radiolabeled somatostatin analog has good showing in midgut neuroendocrine tumors
The radiolabeled somatostatin analog 177Lu-Dotatate is efficacious and safe in patients with previously treated advanced midgut neuroendocrine tumors, according to results of the randomized NETTER-1 trial.
Among the 230 patients studied in the phase III trial, compared with peers given high-dose octreotide LAR, patients given 177Lu-Dotatate had a 79% reduction in the risk of progression or death, lead study author Dr. Jonathan R. Strosberg reported in a presscast leading up to the Gastrointestinal Cancers Symposium.
In addition, 18% of patients had a complete or partial response to the radiolabeled analog, which is considered to be a type of peptide receptor radiotherapy. And there was a trend toward better survival with the radiolabeled analog in an interim analysis.
177Lu-Dotatate had a good safety profile, with somewhat higher rates of gastrointestinal adverse events (likely related to an amino acid infusion given along with the agent) and lymphopenia. Regarding leukemia and myelodysplastic syndrome, “the bottom line is that there were only two very questionable myelodysplastic symptom events seen so far. It’s not clear whether it’s true MDS or whether it’s related to therapy,” said Dr. Strosberg of the Moffitt Cancer Center, Tampa, Fla.
“While there have been few available systemic treatment options for patients progressing on first-line somatostatin analogs, [177Lu-Dotatate] appears to have a major therapeutic benefit in this patient population,” he said ahead of the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
Everolimus is also likely to be increasingly used in this therapeutic space, given positive results of the RADIANT-4 trial, including a subgroup analysis being reported at the symposium, Dr. Strosberg acknowledged.
“I think there is going to be a lot of debate on whether 177Lu-Dotatate or everolimus should be used in the average patient that progresses on a first-line somatostatin analog,” he said. “I would argue if there is a predictive factor, it may be somatostatin receptor expression. Patients who express a lot of somatostatin receptors on their scans will probably have a high likelihood of doing well with peptide receptor radiotherapy.”
ASCO expert and presscast moderator Dr. Smitha Krishnamurthi of Case Western Reserve University, Cleveland, said, “177Lu-Dotatate showed impressive ability to slow the growth of midgut neuroendocrine tumors that have progressed on somatostatin analog therapy. Also notable was that the 177Lu-Dotatate resulted in a response rate of 18% in these tumors, which are typically unresponsive to systemic therapy. The trend toward improvement in overall survival was also encouraging.
“This tumor-targeted peptide receptor radionuclide therapy represents a new modality of anticancer treatment,” she maintained.
Patients were eligible for NETTER-1 – the first randomized trial of a radiolabeled somatostatin analog in this setting – if they had inoperable, somatostatin receptor–positive neuroendocrine tumors of the midgut (small intestine or proximal colon) that had progressed despite treatment with octreotide LAR at the standard dose of 30 mg.
They were randomized evenly to 177Lu-Dotatate (Lutathera), one treatment every 8 weeks for a total of four treatments, or to octreotide LAR (Sandostatin LAR) 60 mg every 4 weeks.
In results that Dr. Strosberg called “extremely impressive,” median estimated progression-free survival was not reached but expected to be about 40 months with 177Lu-Dotatate, compared with 8 months with high-dose octreotide. The difference corresponded to a sharply reduced risk of events with the radiolabeled analog (hazard ratio, 0.21; P less than .0001).
The objective response rate was 18% with 177Lu-Dotatate, compared with just 3% with high-dose octreotide (P = .0008).
“Most studies have shown response rates in the single digits,” he noted. “This is really the only large study that has shown a double-digit objective response rate in a population with midgut neuroendocrine tumors.”
An interim analysis of overall survival found that there were 13 deaths with 177Lu-Dotatate and 22 with high-dose octreotide, but longer follow-up is needed.
Grade 3 or 4 lymphopenia was more common with the radiolabeled analog (9% vs. 0%), as were grade 3 or 4 nausea (4% vs. 2%) and vomiting (7% vs. 0%).
“I would say most of the gastrointestinal side effects are related actually to the amino acid infusions that were used as nephroprotective drugs in combination with the [177Lu-Dotatate]. The trial mandated use of commercial formulations of the drugs, which are quite nauseating,” Dr. Strosberg said. “In Europe, they use modified amino acid formulations, which are much less nauseating.”
“The good thing is that the nausea and vomiting typically resolved when the amino acid infusion was discontinued,” he added.
The radiolabeled somatostatin analog 177Lu-Dotatate is efficacious and safe in patients with previously treated advanced midgut neuroendocrine tumors, according to results of the randomized NETTER-1 trial.
Among the 230 patients studied in the phase III trial, compared with peers given high-dose octreotide LAR, patients given 177Lu-Dotatate had a 79% reduction in the risk of progression or death, lead study author Dr. Jonathan R. Strosberg reported in a presscast leading up to the Gastrointestinal Cancers Symposium.
In addition, 18% of patients had a complete or partial response to the radiolabeled analog, which is considered to be a type of peptide receptor radiotherapy. And there was a trend toward better survival with the radiolabeled analog in an interim analysis.
177Lu-Dotatate had a good safety profile, with somewhat higher rates of gastrointestinal adverse events (likely related to an amino acid infusion given along with the agent) and lymphopenia. Regarding leukemia and myelodysplastic syndrome, “the bottom line is that there were only two very questionable myelodysplastic symptom events seen so far. It’s not clear whether it’s true MDS or whether it’s related to therapy,” said Dr. Strosberg of the Moffitt Cancer Center, Tampa, Fla.
“While there have been few available systemic treatment options for patients progressing on first-line somatostatin analogs, [177Lu-Dotatate] appears to have a major therapeutic benefit in this patient population,” he said ahead of the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
Everolimus is also likely to be increasingly used in this therapeutic space, given positive results of the RADIANT-4 trial, including a subgroup analysis being reported at the symposium, Dr. Strosberg acknowledged.
“I think there is going to be a lot of debate on whether 177Lu-Dotatate or everolimus should be used in the average patient that progresses on a first-line somatostatin analog,” he said. “I would argue if there is a predictive factor, it may be somatostatin receptor expression. Patients who express a lot of somatostatin receptors on their scans will probably have a high likelihood of doing well with peptide receptor radiotherapy.”
ASCO expert and presscast moderator Dr. Smitha Krishnamurthi of Case Western Reserve University, Cleveland, said, “177Lu-Dotatate showed impressive ability to slow the growth of midgut neuroendocrine tumors that have progressed on somatostatin analog therapy. Also notable was that the 177Lu-Dotatate resulted in a response rate of 18% in these tumors, which are typically unresponsive to systemic therapy. The trend toward improvement in overall survival was also encouraging.
“This tumor-targeted peptide receptor radionuclide therapy represents a new modality of anticancer treatment,” she maintained.
Patients were eligible for NETTER-1 – the first randomized trial of a radiolabeled somatostatin analog in this setting – if they had inoperable, somatostatin receptor–positive neuroendocrine tumors of the midgut (small intestine or proximal colon) that had progressed despite treatment with octreotide LAR at the standard dose of 30 mg.
They were randomized evenly to 177Lu-Dotatate (Lutathera), one treatment every 8 weeks for a total of four treatments, or to octreotide LAR (Sandostatin LAR) 60 mg every 4 weeks.
In results that Dr. Strosberg called “extremely impressive,” median estimated progression-free survival was not reached but expected to be about 40 months with 177Lu-Dotatate, compared with 8 months with high-dose octreotide. The difference corresponded to a sharply reduced risk of events with the radiolabeled analog (hazard ratio, 0.21; P less than .0001).
The objective response rate was 18% with 177Lu-Dotatate, compared with just 3% with high-dose octreotide (P = .0008).
“Most studies have shown response rates in the single digits,” he noted. “This is really the only large study that has shown a double-digit objective response rate in a population with midgut neuroendocrine tumors.”
An interim analysis of overall survival found that there were 13 deaths with 177Lu-Dotatate and 22 with high-dose octreotide, but longer follow-up is needed.
Grade 3 or 4 lymphopenia was more common with the radiolabeled analog (9% vs. 0%), as were grade 3 or 4 nausea (4% vs. 2%) and vomiting (7% vs. 0%).
“I would say most of the gastrointestinal side effects are related actually to the amino acid infusions that were used as nephroprotective drugs in combination with the [177Lu-Dotatate]. The trial mandated use of commercial formulations of the drugs, which are quite nauseating,” Dr. Strosberg said. “In Europe, they use modified amino acid formulations, which are much less nauseating.”
“The good thing is that the nausea and vomiting typically resolved when the amino acid infusion was discontinued,” he added.
The radiolabeled somatostatin analog 177Lu-Dotatate is efficacious and safe in patients with previously treated advanced midgut neuroendocrine tumors, according to results of the randomized NETTER-1 trial.
Among the 230 patients studied in the phase III trial, compared with peers given high-dose octreotide LAR, patients given 177Lu-Dotatate had a 79% reduction in the risk of progression or death, lead study author Dr. Jonathan R. Strosberg reported in a presscast leading up to the Gastrointestinal Cancers Symposium.
In addition, 18% of patients had a complete or partial response to the radiolabeled analog, which is considered to be a type of peptide receptor radiotherapy. And there was a trend toward better survival with the radiolabeled analog in an interim analysis.
177Lu-Dotatate had a good safety profile, with somewhat higher rates of gastrointestinal adverse events (likely related to an amino acid infusion given along with the agent) and lymphopenia. Regarding leukemia and myelodysplastic syndrome, “the bottom line is that there were only two very questionable myelodysplastic symptom events seen so far. It’s not clear whether it’s true MDS or whether it’s related to therapy,” said Dr. Strosberg of the Moffitt Cancer Center, Tampa, Fla.
“While there have been few available systemic treatment options for patients progressing on first-line somatostatin analogs, [177Lu-Dotatate] appears to have a major therapeutic benefit in this patient population,” he said ahead of the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
Everolimus is also likely to be increasingly used in this therapeutic space, given positive results of the RADIANT-4 trial, including a subgroup analysis being reported at the symposium, Dr. Strosberg acknowledged.
“I think there is going to be a lot of debate on whether 177Lu-Dotatate or everolimus should be used in the average patient that progresses on a first-line somatostatin analog,” he said. “I would argue if there is a predictive factor, it may be somatostatin receptor expression. Patients who express a lot of somatostatin receptors on their scans will probably have a high likelihood of doing well with peptide receptor radiotherapy.”
ASCO expert and presscast moderator Dr. Smitha Krishnamurthi of Case Western Reserve University, Cleveland, said, “177Lu-Dotatate showed impressive ability to slow the growth of midgut neuroendocrine tumors that have progressed on somatostatin analog therapy. Also notable was that the 177Lu-Dotatate resulted in a response rate of 18% in these tumors, which are typically unresponsive to systemic therapy. The trend toward improvement in overall survival was also encouraging.
“This tumor-targeted peptide receptor radionuclide therapy represents a new modality of anticancer treatment,” she maintained.
Patients were eligible for NETTER-1 – the first randomized trial of a radiolabeled somatostatin analog in this setting – if they had inoperable, somatostatin receptor–positive neuroendocrine tumors of the midgut (small intestine or proximal colon) that had progressed despite treatment with octreotide LAR at the standard dose of 30 mg.
They were randomized evenly to 177Lu-Dotatate (Lutathera), one treatment every 8 weeks for a total of four treatments, or to octreotide LAR (Sandostatin LAR) 60 mg every 4 weeks.
In results that Dr. Strosberg called “extremely impressive,” median estimated progression-free survival was not reached but expected to be about 40 months with 177Lu-Dotatate, compared with 8 months with high-dose octreotide. The difference corresponded to a sharply reduced risk of events with the radiolabeled analog (hazard ratio, 0.21; P less than .0001).
The objective response rate was 18% with 177Lu-Dotatate, compared with just 3% with high-dose octreotide (P = .0008).
“Most studies have shown response rates in the single digits,” he noted. “This is really the only large study that has shown a double-digit objective response rate in a population with midgut neuroendocrine tumors.”
An interim analysis of overall survival found that there were 13 deaths with 177Lu-Dotatate and 22 with high-dose octreotide, but longer follow-up is needed.
Grade 3 or 4 lymphopenia was more common with the radiolabeled analog (9% vs. 0%), as were grade 3 or 4 nausea (4% vs. 2%) and vomiting (7% vs. 0%).
“I would say most of the gastrointestinal side effects are related actually to the amino acid infusions that were used as nephroprotective drugs in combination with the [177Lu-Dotatate]. The trial mandated use of commercial formulations of the drugs, which are quite nauseating,” Dr. Strosberg said. “In Europe, they use modified amino acid formulations, which are much less nauseating.”
“The good thing is that the nausea and vomiting typically resolved when the amino acid infusion was discontinued,” he added.
FROM THE GASTROINTESTINAL CANCERS SYMPOSIUM
Key clinical point: 177Lu-Dotatate appears efficacious and safe for the treatment of advanced midgut neuroendocrine tumors.
Major finding: Median progression-free survival was expected to be about 40 months with 177Lu-Dotatate, compared with 8 months with high-dose octreotide LAR.
Data source: A randomized phase III trial among 230 patients with previously treated advanced midgut neuroendocrine tumors (NETTER-1 trial).
Disclosures: Dr. Strosberg disclosed that he had no relevant conflicts of interest. The study received funding from Advanced Accelerator Applications.