Among Asian women with hormone receptor–positive/human epidermal growth factor receptor-2 (HER2)–negative metastatic breast cancer that is resistant to endocrine therapy, a combination of palbociclib (Ibrance) and fulvestrant (Faslodex) was associated with a significant improvement in progression-free survival (PFS), reported investigators from the PALOMA-3 trial.

A preplanned subgroup analysis of 102 pre- and postmenopausal women from Japan, South Korea, and Taiwan who were enrolled in the trial showed that median PFS for 71 women assigned to palbociclib and fulvestrant had not been reached at the trial end. In contrast, median PFS among 31 patients assigned to placebo and fulvestrant was 5.8 months (hazard ratio, 0.485; P = .0065), reported Hiroji Iwata, MD, PhD, of the Aichi Cancer Center Hospital in Nagoya, Japan, and his colleagues.

“Overall, palbociclib plus fulvestrant seems to be a reasonable treatment option in Asians with HR-positive/HER2-negative metastatic breast cancer that has progressed on prior endocrine therapy,” they wrote in the Journal of Global Oncology (2017 Apr 11. doi: 10.1200/JGO.2016.008318).

PALOMA-3 was a multinational randomized double-blind, placebo-controlled phase III trial comparing a combination of fulvestrant, a selective estrogen receptor downregulator, and palbociclib, a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) with fulvestrant plus placebo in 521 women with HR-positive/HER2-negative advanced breast cancer.

The trial was halted early for efficacy of the combination. The final overall analysis, published in April 2016 in The Lancet Oncology, showed that the combination significantly improved PFS, compared with fulvestrant and placebo, regardless of the patients’ degree of endocrine resistance, level of hormone receptor expression level, or PIK3CA mutational status.

Dr. Iwata and his associates noted that breast cancer is generally diagnosed at a younger age among Asian women (median, 45-50 years vs. 55-60 years among Western women) and that differences in genetic backgrounds may influence drug metabolism, resulting in potential differences in efficacy and adverse event profiles.

Among patients treated with palbociclib, the most common grade 3 or higher adverse events were neutropenia in 92%, compared with none in the placebo arm, and leukopenia in 29% vs. 0%. In contrast, grade 3/4 neutropenia occurred in 58% of non-Asian patients treated with the combination and 0.7% of non-Asian controls. Leukopenia rates were similar between Asian and non-Asian populations, however.

Comparisons of mean trough concentrations across subgroups showed that palbociclib exposures among Asians and non-Asians were similar. Patient reported outcomes were also similar between the groups, except for significantly more dyspnea among patients who received palbociclib (P = .05).

“This study adds to the limited body of literature assessing a CDK4/6 inhibitor in Asians and represents the largest patient experience with palbociclib in Asians. The present findings show that palbociclib plus fulvestrant improved PFS in Asians with HR-positive/HER2-negative [metastatic breast cancer] who experienced progression on prior endocrine therapy and that the safety profile of palbociclib plus fulvestrant in Asians was generally consistent with that observed in non-Asians. Together, these findings suggest that palbociclib is beneficial in patients who have not previously received endocrine therapy and in Asians and non-Asians who experienced relapse or progression during prior endocrine therapy,” they wrote.

The PALOMA-3 trial was supported by Pfizer. Dr. Iwata disclosed consultations with Chugai Pharma, Eisai, and AstraZeneca. Several coauthors are Pfizer employees and shareholders.

Among Asian women with hormone receptor–positive/human epidermal growth factor receptor-2 (HER2)–negative metastatic breast cancer that is resistant to endocrine therapy, a combination of palbociclib (Ibrance) and fulvestrant (Faslodex) was associated with a significant improvement in progression-free survival (PFS), reported investigators from the PALOMA-3 trial.

A preplanned subgroup analysis of 102 pre- and postmenopausal women from Japan, South Korea, and Taiwan who were enrolled in the trial showed that median PFS for 71 women assigned to palbociclib and fulvestrant had not been reached at the trial end. In contrast, median PFS among 31 patients assigned to placebo and fulvestrant was 5.8 months (hazard ratio, 0.485; P = .0065), reported Hiroji Iwata, MD, PhD, of the Aichi Cancer Center Hospital in Nagoya, Japan, and his colleagues.

“Overall, palbociclib plus fulvestrant seems to be a reasonable treatment option in Asians with HR-positive/HER2-negative metastatic breast cancer that has progressed on prior endocrine therapy,” they wrote in the Journal of Global Oncology (2017 Apr 11. doi: 10.1200/JGO.2016.008318).

PALOMA-3 was a multinational randomized double-blind, placebo-controlled phase III trial comparing a combination of fulvestrant, a selective estrogen receptor downregulator, and palbociclib, a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) with fulvestrant plus placebo in 521 women with HR-positive/HER2-negative advanced breast cancer.

The trial was halted early for efficacy of the combination. The final overall analysis, published in April 2016 in The Lancet Oncology, showed that the combination significantly improved PFS, compared with fulvestrant and placebo, regardless of the patients’ degree of endocrine resistance, level of hormone receptor expression level, or PIK3CA mutational status.

Dr. Iwata and his associates noted that breast cancer is generally diagnosed at a younger age among Asian women (median, 45-50 years vs. 55-60 years among Western women) and that differences in genetic backgrounds may influence drug metabolism, resulting in potential differences in efficacy and adverse event profiles.

Among patients treated with palbociclib, the most common grade 3 or higher adverse events were neutropenia in 92%, compared with none in the placebo arm, and leukopenia in 29% vs. 0%. In contrast, grade 3/4 neutropenia occurred in 58% of non-Asian patients treated with the combination and 0.7% of non-Asian controls. Leukopenia rates were similar between Asian and non-Asian populations, however.

Comparisons of mean trough concentrations across subgroups showed that palbociclib exposures among Asians and non-Asians were similar. Patient reported outcomes were also similar between the groups, except for significantly more dyspnea among patients who received palbociclib (P = .05).

“This study adds to the limited body of literature assessing a CDK4/6 inhibitor in Asians and represents the largest patient experience with palbociclib in Asians. The present findings show that palbociclib plus fulvestrant improved PFS in Asians with HR-positive/HER2-negative [metastatic breast cancer] who experienced progression on prior endocrine therapy and that the safety profile of palbociclib plus fulvestrant in Asians was generally consistent with that observed in non-Asians. Together, these findings suggest that palbociclib is beneficial in patients who have not previously received endocrine therapy and in Asians and non-Asians who experienced relapse or progression during prior endocrine therapy,” they wrote.

The PALOMA-3 trial was supported by Pfizer. Dr. Iwata disclosed consultations with Chugai Pharma, Eisai, and AstraZeneca. Several coauthors are Pfizer employees and shareholders.

Among Asian women with hormone receptor–positive/human epidermal growth factor receptor-2 (HER2)–negative metastatic breast cancer that is resistant to endocrine therapy, a combination of palbociclib (Ibrance) and fulvestrant (Faslodex) was associated with a significant improvement in progression-free survival (PFS), reported investigators from the PALOMA-3 trial.

A preplanned subgroup analysis of 102 pre- and postmenopausal women from Japan, South Korea, and Taiwan who were enrolled in the trial showed that median PFS for 71 women assigned to palbociclib and fulvestrant had not been reached at the trial end. In contrast, median PFS among 31 patients assigned to placebo and fulvestrant was 5.8 months (hazard ratio, 0.485; P = .0065), reported Hiroji Iwata, MD, PhD, of the Aichi Cancer Center Hospital in Nagoya, Japan, and his colleagues.

“Overall, palbociclib plus fulvestrant seems to be a reasonable treatment option in Asians with HR-positive/HER2-negative metastatic breast cancer that has progressed on prior endocrine therapy,” they wrote in the Journal of Global Oncology (2017 Apr 11. doi: 10.1200/JGO.2016.008318).

PALOMA-3 was a multinational randomized double-blind, placebo-controlled phase III trial comparing a combination of fulvestrant, a selective estrogen receptor downregulator, and palbociclib, a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) with fulvestrant plus placebo in 521 women with HR-positive/HER2-negative advanced breast cancer.

The trial was halted early for efficacy of the combination. The final overall analysis, published in April 2016 in The Lancet Oncology, showed that the combination significantly improved PFS, compared with fulvestrant and placebo, regardless of the patients’ degree of endocrine resistance, level of hormone receptor expression level, or PIK3CA mutational status.

Dr. Iwata and his associates noted that breast cancer is generally diagnosed at a younger age among Asian women (median, 45-50 years vs. 55-60 years among Western women) and that differences in genetic backgrounds may influence drug metabolism, resulting in potential differences in efficacy and adverse event profiles.

Among patients treated with palbociclib, the most common grade 3 or higher adverse events were neutropenia in 92%, compared with none in the placebo arm, and leukopenia in 29% vs. 0%. In contrast, grade 3/4 neutropenia occurred in 58% of non-Asian patients treated with the combination and 0.7% of non-Asian controls. Leukopenia rates were similar between Asian and non-Asian populations, however.

Comparisons of mean trough concentrations across subgroups showed that palbociclib exposures among Asians and non-Asians were similar. Patient reported outcomes were also similar between the groups, except for significantly more dyspnea among patients who received palbociclib (P = .05).

“This study adds to the limited body of literature assessing a CDK4/6 inhibitor in Asians and represents the largest patient experience with palbociclib in Asians. The present findings show that palbociclib plus fulvestrant improved PFS in Asians with HR-positive/HER2-negative [metastatic breast cancer] who experienced progression on prior endocrine therapy and that the safety profile of palbociclib plus fulvestrant in Asians was generally consistent with that observed in non-Asians. Together, these findings suggest that palbociclib is beneficial in patients who have not previously received endocrine therapy and in Asians and non-Asians who experienced relapse or progression during prior endocrine therapy,” they wrote.

The PALOMA-3 trial was supported by Pfizer. Dr. Iwata disclosed consultations with Chugai Pharma, Eisai, and AstraZeneca. Several coauthors are Pfizer employees and shareholders.

ORLANDO – Overall cancer death rates are dropping dramatically, but pancreatic cancer mortality remains high.

“By 2020 we expect [pancreatic cancer] to be the second most common cause of cancer-related death, exceeded only by lung cancer, and if lung cancer deaths continue to fall – which we expect that they will – it will be the most common cause of cancer-related death,” Margaret A. Tempero, MD, said at the annual conference of the National Comprehensive Cancer Network.

Further, as the population ages there will be an increasing number of patients presenting with pancreatic cancer, said Dr. Tempero of the University of California, San Francisco.

Courtesy Dr. Lance Liotta Laboratory

Resectable/borderline resectable disease

One noteworthy recent advance for patients with resectable/borderline resectable disease is the addition of capecitabine to gemcitabine for adjuvant therapy. In the ESPAC 4 study published in March in the Lancet, the combination of gemcitabine and capecitabine showed a clear benefit over gemcitabine alone.

“So that has now entered [the NCCN] guidelines as an important option for adjuvant therapy,” said Dr. Tempero, chair of the NCCN pancreatic cancer guidelines panel.

Ongoing trials are also looking at the FOLFIRINOX (irinotecan plus 5-fluorouracil plus leucovorin plus oxaliplatin) and gemcitabine/nanoparticle albumin-bound paclitaxel (nab-P) regimens in the adjuvant setting. These have previously shown some efficacy in the metastatic setting.

“So we really wanted to get these therapies into the adjuvant setting as soon as we could,” she said.

In the ACCORD trial, FOLFIRINOX is being compared with gemcitabine in the postoperative adjuvant setting, and the APACT trial comparing gemcitabine/nab-P to gemcitabine monotherapy completed accrual last year.

“I’m pretty sure that we’ll have enough events on the APACT study by the end of this year, and hopefully we can present that data in the spring. I’m hoping it will be a positive trial for us,” she said.

Neoadjuvant therapy – a successful strategy used in many other malignancies – is also being looked at for pancreatic cancer.

A pilot study (A021101) completed last year suggested that chemotherapy (FOLFIRINOX for 2 months) and chemoradiation (capecitabine and radiation at 50.4 Gy) followed by surgical resection and adjuvant chemotherapy (gemcitabine for 2 months) provided some benefit in patients with borderline resectable pancreatic cancer. This trial led to another ongoing study (S1505) in which patients with borderline resectable disease will be treated with 4 months of FOLFIRINOX prior to resection, followed by chemoradiation and surgery or FOLFIRINOX and surgery, and patients with resectable disease will undergo resection followed by FOLFIRINOX and surgery or gemcitabine/nab-P and surgery.

“The goal is not to compare the two regimens; the goal is to identify the benchmarks that we get with these regimens. In other words, if you’re going to give FOLFIRINOX, what pathologic complete response rate can you expect? What will your R1 resection rate be? With gemcitabine and nab-paclitaxel, the same thing, because if you want to continue to build on these regimens in the neoadjuvant setting you need to know what you’re likely to get so you can make clinical trial assumptions when you add new drugs.

“Once we have these benchmarking data we can really sail in the neoadjuvant setting. It’s a great window-of-opportunity setting for new drugs, because you’re getting serial tissue,” Dr. Tempero said, explaining that in addition to resection of tissue, there is opportunity to get biopsies ahead of time and look at the effects of the drug.

Locally advanced disease

For locally advanced disease, studies have failed to show a benefit of adding radiation after chemotherapy, but radiation oncologists who argue that, “when your therapy gets better, my therapy gets better,” have a valid point, Dr. Tempero said.

For that reason, the Radiation Therapy Oncology group launched a trial to look at gemcitabine/nab-P with and without radiation, but had difficulty with enrollment due to resistance among some physicians who are opposed to radiation in this setting .

“So I don’t know that we will ever answer this question in locally advanced disease. What I can say ... is, in my mind, in locally advanced disease, the most important component is the chemotherapy,” she said.

Metastatic disease

When it comes to trials involving pancreatic cancer patients with metastatic disease, it is important to understand – and to convey to policymakers – that the goal is not only to provide better care in these patients who are at the end of their life, but also to identify strategies that can be used in the adjuvant and neoadjuvant settings, as this is part of the “overall mission of helping patients to feel better and live longer and be cured,” Dr. Tempero said.

One regimen currently used in the metastatic setting is FOLFIRINOX, which was shown in the Prodige 4-ACCORD 11 trial to be superior to gemcitabine monotherapy for survival (hazard ratio, 0.57).

“This is the first time we ever saw a hazard ratio below 0.6 in this disease,” she said, adding that for some patients this means “they can get tremendous benefit, they can come off chemotherapy and have a chemotherapy holiday,” she said.

That said, it’s a tough regimen, she added, explaining that it has dominating toxicities of myelosuppression, diarrhea, and neuropathy that can be irreversible.

Frail patients may not be able to tolerate the regimen, but modifications to the regimen may help. For example, the 5-fluorourasil bolus is often omitted, and doses are sometimes reduced. Chemotherapy holidays can also be of benefit.

Another regimen for the metastatic setting involves the use of nab-P plus gemcitabine, which was shown in a phase III trial to improve survival (HR for death, 0.72).

The results aren’t quite as dramatic as those seen with FOLFIRINOX, but the regimen is slightly easier to manage, Dr. Tempero said, adding: “It’s still not a walk in the park.”

Myelosuppression, arthralgias, and neuropathy still occur, she explained.

Gemcitabine/capecitabine, which has been shown to improve progression-free survival, can also be used, and may be preferable in elderly patients who aren’t fit enough for the other regimens, she said.

“When I select treatment, I really sit down with the patient, and I look at their comorbidities and let them review the toxicities. They decide,” she said, explaining that she provides recommendations based on their concerns and input. “We do have a conversation and we talk about the goals of treatment, we talk about the toxicities.”

Future efforts for metastatic disease should build upon both FOLFIRINOX and gemcitabine/nab-P, she said.

However, because of the difficulty with administering FOLFIRINOX, only two of the 54 open phase I-III trials ongoing in the United States for metastatic disease incorporate the regimen.

Other treatment options include gemcitabine/cisplatin, GTX (gemcitabine/docetaxel/capecitabine), and gemcitabine/erlotinib. The former remains in the NCCN guidelines, primarily for those with hereditary forms of pancreatic cancer, and in particular for those in the DNA repair pathway (BRCA patients, for example).

“We actually have trials now focusing on just BRCA-related pancreatic cancer,” she said, noting that these patients are “exquisitely sensitive to cisplatin and don’t need a harsh regimen like FOLFIRINOX to get the same benefit.

GTX is a very active regimen, although it has never been compared with gemcitabine monotherapy in a randomized trial. However, because of its clear activity it remains in the NCCN guidelines as an option.

Gemcitabine/erlotinib also remains in the guidelines because of a tiny trial that showed a small benefit, but it is not a preferred combination, she said.

Future therapies

Efforts going forward are focusing on finding drugs that inactivate activated RAS, which is “a really big driver” in many cancers, as well as on addressing the microenvironment (such as the desmoplastic stroma that may help encourage invasion of metastases and/or impede drug delivery to the cancer), Dr. Tempero said.

“So there is a lot of interest right now in various forms of immunotherapy or in stromal remodeling so we can see what impact that has on the progression of this disease,” she said, noting that new agents in registration trials include ibrutinib, laparib, PEGPH20, and insulinlike growth factor 1 (IGF-1) inhibitors, and those in planning stages include chemokine (C-C motif) receptor 2 (CCR2) inhibitors and palbociclib.

“And I think we have opportunities in the maintenance setting and in the neoadjuvant setting to do window-of-opportunity trials where we can test new concepts, where we can get pharmacodynamic and biologic data to understand what these new agents are doing,” she said.

Collaborative effort to identify patients at risk

Population-level screening strategies for pancreatic cancer aren’t feasible because of the relatively low incidence of the disease, but efforts are underway to identify and screen high-risk groups.

“We actually have some tests that you could screen with, but they’re not perfect, and with a disease that occurs at the rate that [pancreatic cancer] does, you can’t screen the whole population, because you will find false positives, and you will cause unnecessary procedures more than you’ll find the cancer, Dr. Tempero said during a meeting with press at the NCCN annual conference.

Instead, it is important to identify and screen only those at high risk, she added.

Such a group might include patients with new-onset diabetes who experience weight loss.

New-onset diabetes can be caused by pancreatic cancer, and weight loss with diabetes is unexpected and should raise a red flag, Dr. Temepero explained, adding that an education gap among community physicians means these patients are sometimes cheered for the weight loss instead – and then they end up in the pancreatic disease clinic with metastatic disease 2 years later.

In an effort to better define and characterize this and other high-risk groups, the National Institute for Diabetes and Digestive and Kidney Diseases and the National Cancer Institute are working together to fund a network of institutions that will develop high-risk cohorts and begin deploying screening strategies. The effort is partly in response to the Recalcitrant Cancer Act passed in 2012 to “force more attention on funding pancreatic cancer research through the branches of the NIH,” she explained.

In this particular high-risk group, the institutions will look at the character of diabetes and the clinical correlates with pancreatic cancer.

“Once we hone in on these, we can use those – what we hope are – early-detection biomarkers, and if those are positive, then we would ask the patient to have a CT scan to look for pancreatic cancer,” she said.

Dr. Tempero reported serving as a scientific advisor and/or receiving grant/research support, consulting fees, and/or honoraria from Celgene Corporation, Champion Oncology, Cornerstone Pharmaceuticals, Eli Lilly, EMD Serono, Gilead Sciences, Halozyme Therapeutics, MCS Biotech Resources, NeoHealth, Novocure, Opsona Therapeutics, Pfizer, Portola Pharmaceuticals, and Threshold Pharmaceuticals.

[email protected]

ORLANDO – Overall cancer death rates are dropping dramatically, but pancreatic cancer mortality remains high.

“By 2020 we expect [pancreatic cancer] to be the second most common cause of cancer-related death, exceeded only by lung cancer, and if lung cancer deaths continue to fall – which we expect that they will – it will be the most common cause of cancer-related death,” Margaret A. Tempero, MD, said at the annual conference of the National Comprehensive Cancer Network.

Further, as the population ages there will be an increasing number of patients presenting with pancreatic cancer, said Dr. Tempero of the University of California, San Francisco.

Courtesy Dr. Lance Liotta Laboratory

Resectable/borderline resectable disease

One noteworthy recent advance for patients with resectable/borderline resectable disease is the addition of capecitabine to gemcitabine for adjuvant therapy. In the ESPAC 4 study published in March in the Lancet, the combination of gemcitabine and capecitabine showed a clear benefit over gemcitabine alone.

“So that has now entered [the NCCN] guidelines as an important option for adjuvant therapy,” said Dr. Tempero, chair of the NCCN pancreatic cancer guidelines panel.

Ongoing trials are also looking at the FOLFIRINOX (irinotecan plus 5-fluorouracil plus leucovorin plus oxaliplatin) and gemcitabine/nanoparticle albumin-bound paclitaxel (nab-P) regimens in the adjuvant setting. These have previously shown some efficacy in the metastatic setting.

“So we really wanted to get these therapies into the adjuvant setting as soon as we could,” she said.

In the ACCORD trial, FOLFIRINOX is being compared with gemcitabine in the postoperative adjuvant setting, and the APACT trial comparing gemcitabine/nab-P to gemcitabine monotherapy completed accrual last year.

“I’m pretty sure that we’ll have enough events on the APACT study by the end of this year, and hopefully we can present that data in the spring. I’m hoping it will be a positive trial for us,” she said.

Neoadjuvant therapy – a successful strategy used in many other malignancies – is also being looked at for pancreatic cancer.

A pilot study (A021101) completed last year suggested that chemotherapy (FOLFIRINOX for 2 months) and chemoradiation (capecitabine and radiation at 50.4 Gy) followed by surgical resection and adjuvant chemotherapy (gemcitabine for 2 months) provided some benefit in patients with borderline resectable pancreatic cancer. This trial led to another ongoing study (S1505) in which patients with borderline resectable disease will be treated with 4 months of FOLFIRINOX prior to resection, followed by chemoradiation and surgery or FOLFIRINOX and surgery, and patients with resectable disease will undergo resection followed by FOLFIRINOX and surgery or gemcitabine/nab-P and surgery.

“The goal is not to compare the two regimens; the goal is to identify the benchmarks that we get with these regimens. In other words, if you’re going to give FOLFIRINOX, what pathologic complete response rate can you expect? What will your R1 resection rate be? With gemcitabine and nab-paclitaxel, the same thing, because if you want to continue to build on these regimens in the neoadjuvant setting you need to know what you’re likely to get so you can make clinical trial assumptions when you add new drugs.

“Once we have these benchmarking data we can really sail in the neoadjuvant setting. It’s a great window-of-opportunity setting for new drugs, because you’re getting serial tissue,” Dr. Tempero said, explaining that in addition to resection of tissue, there is opportunity to get biopsies ahead of time and look at the effects of the drug.

Locally advanced disease

For locally advanced disease, studies have failed to show a benefit of adding radiation after chemotherapy, but radiation oncologists who argue that, “when your therapy gets better, my therapy gets better,” have a valid point, Dr. Tempero said.

For that reason, the Radiation Therapy Oncology group launched a trial to look at gemcitabine/nab-P with and without radiation, but had difficulty with enrollment due to resistance among some physicians who are opposed to radiation in this setting .

“So I don’t know that we will ever answer this question in locally advanced disease. What I can say ... is, in my mind, in locally advanced disease, the most important component is the chemotherapy,” she said.

Metastatic disease

When it comes to trials involving pancreatic cancer patients with metastatic disease, it is important to understand – and to convey to policymakers – that the goal is not only to provide better care in these patients who are at the end of their life, but also to identify strategies that can be used in the adjuvant and neoadjuvant settings, as this is part of the “overall mission of helping patients to feel better and live longer and be cured,” Dr. Tempero said.

One regimen currently used in the metastatic setting is FOLFIRINOX, which was shown in the Prodige 4-ACCORD 11 trial to be superior to gemcitabine monotherapy for survival (hazard ratio, 0.57).

“This is the first time we ever saw a hazard ratio below 0.6 in this disease,” she said, adding that for some patients this means “they can get tremendous benefit, they can come off chemotherapy and have a chemotherapy holiday,” she said.

That said, it’s a tough regimen, she added, explaining that it has dominating toxicities of myelosuppression, diarrhea, and neuropathy that can be irreversible.

Frail patients may not be able to tolerate the regimen, but modifications to the regimen may help. For example, the 5-fluorourasil bolus is often omitted, and doses are sometimes reduced. Chemotherapy holidays can also be of benefit.

Another regimen for the metastatic setting involves the use of nab-P plus gemcitabine, which was shown in a phase III trial to improve survival (HR for death, 0.72).

The results aren’t quite as dramatic as those seen with FOLFIRINOX, but the regimen is slightly easier to manage, Dr. Tempero said, adding: “It’s still not a walk in the park.”

Myelosuppression, arthralgias, and neuropathy still occur, she explained.

Gemcitabine/capecitabine, which has been shown to improve progression-free survival, can also be used, and may be preferable in elderly patients who aren’t fit enough for the other regimens, she said.

“When I select treatment, I really sit down with the patient, and I look at their comorbidities and let them review the toxicities. They decide,” she said, explaining that she provides recommendations based on their concerns and input. “We do have a conversation and we talk about the goals of treatment, we talk about the toxicities.”

Future efforts for metastatic disease should build upon both FOLFIRINOX and gemcitabine/nab-P, she said.

However, because of the difficulty with administering FOLFIRINOX, only two of the 54 open phase I-III trials ongoing in the United States for metastatic disease incorporate the regimen.

Other treatment options include gemcitabine/cisplatin, GTX (gemcitabine/docetaxel/capecitabine), and gemcitabine/erlotinib. The former remains in the NCCN guidelines, primarily for those with hereditary forms of pancreatic cancer, and in particular for those in the DNA repair pathway (BRCA patients, for example).

“We actually have trials now focusing on just BRCA-related pancreatic cancer,” she said, noting that these patients are “exquisitely sensitive to cisplatin and don’t need a harsh regimen like FOLFIRINOX to get the same benefit.

GTX is a very active regimen, although it has never been compared with gemcitabine monotherapy in a randomized trial. However, because of its clear activity it remains in the NCCN guidelines as an option.

Gemcitabine/erlotinib also remains in the guidelines because of a tiny trial that showed a small benefit, but it is not a preferred combination, she said.

Future therapies

Efforts going forward are focusing on finding drugs that inactivate activated RAS, which is “a really big driver” in many cancers, as well as on addressing the microenvironment (such as the desmoplastic stroma that may help encourage invasion of metastases and/or impede drug delivery to the cancer), Dr. Tempero said.

“So there is a lot of interest right now in various forms of immunotherapy or in stromal remodeling so we can see what impact that has on the progression of this disease,” she said, noting that new agents in registration trials include ibrutinib, laparib, PEGPH20, and insulinlike growth factor 1 (IGF-1) inhibitors, and those in planning stages include chemokine (C-C motif) receptor 2 (CCR2) inhibitors and palbociclib.

“And I think we have opportunities in the maintenance setting and in the neoadjuvant setting to do window-of-opportunity trials where we can test new concepts, where we can get pharmacodynamic and biologic data to understand what these new agents are doing,” she said.

Collaborative effort to identify patients at risk

Population-level screening strategies for pancreatic cancer aren’t feasible because of the relatively low incidence of the disease, but efforts are underway to identify and screen high-risk groups.

“We actually have some tests that you could screen with, but they’re not perfect, and with a disease that occurs at the rate that [pancreatic cancer] does, you can’t screen the whole population, because you will find false positives, and you will cause unnecessary procedures more than you’ll find the cancer, Dr. Tempero said during a meeting with press at the NCCN annual conference.

Instead, it is important to identify and screen only those at high risk, she added.

Such a group might include patients with new-onset diabetes who experience weight loss.

New-onset diabetes can be caused by pancreatic cancer, and weight loss with diabetes is unexpected and should raise a red flag, Dr. Temepero explained, adding that an education gap among community physicians means these patients are sometimes cheered for the weight loss instead – and then they end up in the pancreatic disease clinic with metastatic disease 2 years later.

In an effort to better define and characterize this and other high-risk groups, the National Institute for Diabetes and Digestive and Kidney Diseases and the National Cancer Institute are working together to fund a network of institutions that will develop high-risk cohorts and begin deploying screening strategies. The effort is partly in response to the Recalcitrant Cancer Act passed in 2012 to “force more attention on funding pancreatic cancer research through the branches of the NIH,” she explained.

In this particular high-risk group, the institutions will look at the character of diabetes and the clinical correlates with pancreatic cancer.

“Once we hone in on these, we can use those – what we hope are – early-detection biomarkers, and if those are positive, then we would ask the patient to have a CT scan to look for pancreatic cancer,” she said.

Dr. Tempero reported serving as a scientific advisor and/or receiving grant/research support, consulting fees, and/or honoraria from Celgene Corporation, Champion Oncology, Cornerstone Pharmaceuticals, Eli Lilly, EMD Serono, Gilead Sciences, Halozyme Therapeutics, MCS Biotech Resources, NeoHealth, Novocure, Opsona Therapeutics, Pfizer, Portola Pharmaceuticals, and Threshold Pharmaceuticals.

[email protected]

ORLANDO – Overall cancer death rates are dropping dramatically, but pancreatic cancer mortality remains high.

“By 2020 we expect [pancreatic cancer] to be the second most common cause of cancer-related death, exceeded only by lung cancer, and if lung cancer deaths continue to fall – which we expect that they will – it will be the most common cause of cancer-related death,” Margaret A. Tempero, MD, said at the annual conference of the National Comprehensive Cancer Network.

Further, as the population ages there will be an increasing number of patients presenting with pancreatic cancer, said Dr. Tempero of the University of California, San Francisco.

Courtesy Dr. Lance Liotta Laboratory

Resectable/borderline resectable disease

One noteworthy recent advance for patients with resectable/borderline resectable disease is the addition of capecitabine to gemcitabine for adjuvant therapy. In the ESPAC 4 study published in March in the Lancet, the combination of gemcitabine and capecitabine showed a clear benefit over gemcitabine alone.

“So that has now entered [the NCCN] guidelines as an important option for adjuvant therapy,” said Dr. Tempero, chair of the NCCN pancreatic cancer guidelines panel.

Ongoing trials are also looking at the FOLFIRINOX (irinotecan plus 5-fluorouracil plus leucovorin plus oxaliplatin) and gemcitabine/nanoparticle albumin-bound paclitaxel (nab-P) regimens in the adjuvant setting. These have previously shown some efficacy in the metastatic setting.

“So we really wanted to get these therapies into the adjuvant setting as soon as we could,” she said.

In the ACCORD trial, FOLFIRINOX is being compared with gemcitabine in the postoperative adjuvant setting, and the APACT trial comparing gemcitabine/nab-P to gemcitabine monotherapy completed accrual last year.

“I’m pretty sure that we’ll have enough events on the APACT study by the end of this year, and hopefully we can present that data in the spring. I’m hoping it will be a positive trial for us,” she said.

Neoadjuvant therapy – a successful strategy used in many other malignancies – is also being looked at for pancreatic cancer.

A pilot study (A021101) completed last year suggested that chemotherapy (FOLFIRINOX for 2 months) and chemoradiation (capecitabine and radiation at 50.4 Gy) followed by surgical resection and adjuvant chemotherapy (gemcitabine for 2 months) provided some benefit in patients with borderline resectable pancreatic cancer. This trial led to another ongoing study (S1505) in which patients with borderline resectable disease will be treated with 4 months of FOLFIRINOX prior to resection, followed by chemoradiation and surgery or FOLFIRINOX and surgery, and patients with resectable disease will undergo resection followed by FOLFIRINOX and surgery or gemcitabine/nab-P and surgery.

“The goal is not to compare the two regimens; the goal is to identify the benchmarks that we get with these regimens. In other words, if you’re going to give FOLFIRINOX, what pathologic complete response rate can you expect? What will your R1 resection rate be? With gemcitabine and nab-paclitaxel, the same thing, because if you want to continue to build on these regimens in the neoadjuvant setting you need to know what you’re likely to get so you can make clinical trial assumptions when you add new drugs.

“Once we have these benchmarking data we can really sail in the neoadjuvant setting. It’s a great window-of-opportunity setting for new drugs, because you’re getting serial tissue,” Dr. Tempero said, explaining that in addition to resection of tissue, there is opportunity to get biopsies ahead of time and look at the effects of the drug.

Locally advanced disease

For locally advanced disease, studies have failed to show a benefit of adding radiation after chemotherapy, but radiation oncologists who argue that, “when your therapy gets better, my therapy gets better,” have a valid point, Dr. Tempero said.

For that reason, the Radiation Therapy Oncology group launched a trial to look at gemcitabine/nab-P with and without radiation, but had difficulty with enrollment due to resistance among some physicians who are opposed to radiation in this setting .

“So I don’t know that we will ever answer this question in locally advanced disease. What I can say ... is, in my mind, in locally advanced disease, the most important component is the chemotherapy,” she said.

Metastatic disease

When it comes to trials involving pancreatic cancer patients with metastatic disease, it is important to understand – and to convey to policymakers – that the goal is not only to provide better care in these patients who are at the end of their life, but also to identify strategies that can be used in the adjuvant and neoadjuvant settings, as this is part of the “overall mission of helping patients to feel better and live longer and be cured,” Dr. Tempero said.

One regimen currently used in the metastatic setting is FOLFIRINOX, which was shown in the Prodige 4-ACCORD 11 trial to be superior to gemcitabine monotherapy for survival (hazard ratio, 0.57).

“This is the first time we ever saw a hazard ratio below 0.6 in this disease,” she said, adding that for some patients this means “they can get tremendous benefit, they can come off chemotherapy and have a chemotherapy holiday,” she said.

That said, it’s a tough regimen, she added, explaining that it has dominating toxicities of myelosuppression, diarrhea, and neuropathy that can be irreversible.

Frail patients may not be able to tolerate the regimen, but modifications to the regimen may help. For example, the 5-fluorourasil bolus is often omitted, and doses are sometimes reduced. Chemotherapy holidays can also be of benefit.

Another regimen for the metastatic setting involves the use of nab-P plus gemcitabine, which was shown in a phase III trial to improve survival (HR for death, 0.72).

The results aren’t quite as dramatic as those seen with FOLFIRINOX, but the regimen is slightly easier to manage, Dr. Tempero said, adding: “It’s still not a walk in the park.”

Myelosuppression, arthralgias, and neuropathy still occur, she explained.

Gemcitabine/capecitabine, which has been shown to improve progression-free survival, can also be used, and may be preferable in elderly patients who aren’t fit enough for the other regimens, she said.

“When I select treatment, I really sit down with the patient, and I look at their comorbidities and let them review the toxicities. They decide,” she said, explaining that she provides recommendations based on their concerns and input. “We do have a conversation and we talk about the goals of treatment, we talk about the toxicities.”

Future efforts for metastatic disease should build upon both FOLFIRINOX and gemcitabine/nab-P, she said.

However, because of the difficulty with administering FOLFIRINOX, only two of the 54 open phase I-III trials ongoing in the United States for metastatic disease incorporate the regimen.

Other treatment options include gemcitabine/cisplatin, GTX (gemcitabine/docetaxel/capecitabine), and gemcitabine/erlotinib. The former remains in the NCCN guidelines, primarily for those with hereditary forms of pancreatic cancer, and in particular for those in the DNA repair pathway (BRCA patients, for example).

“We actually have trials now focusing on just BRCA-related pancreatic cancer,” she said, noting that these patients are “exquisitely sensitive to cisplatin and don’t need a harsh regimen like FOLFIRINOX to get the same benefit.

GTX is a very active regimen, although it has never been compared with gemcitabine monotherapy in a randomized trial. However, because of its clear activity it remains in the NCCN guidelines as an option.

Gemcitabine/erlotinib also remains in the guidelines because of a tiny trial that showed a small benefit, but it is not a preferred combination, she said.

Future therapies

Efforts going forward are focusing on finding drugs that inactivate activated RAS, which is “a really big driver” in many cancers, as well as on addressing the microenvironment (such as the desmoplastic stroma that may help encourage invasion of metastases and/or impede drug delivery to the cancer), Dr. Tempero said.

“So there is a lot of interest right now in various forms of immunotherapy or in stromal remodeling so we can see what impact that has on the progression of this disease,” she said, noting that new agents in registration trials include ibrutinib, laparib, PEGPH20, and insulinlike growth factor 1 (IGF-1) inhibitors, and those in planning stages include chemokine (C-C motif) receptor 2 (CCR2) inhibitors and palbociclib.

“And I think we have opportunities in the maintenance setting and in the neoadjuvant setting to do window-of-opportunity trials where we can test new concepts, where we can get pharmacodynamic and biologic data to understand what these new agents are doing,” she said.

Collaborative effort to identify patients at risk

Population-level screening strategies for pancreatic cancer aren’t feasible because of the relatively low incidence of the disease, but efforts are underway to identify and screen high-risk groups.

“We actually have some tests that you could screen with, but they’re not perfect, and with a disease that occurs at the rate that [pancreatic cancer] does, you can’t screen the whole population, because you will find false positives, and you will cause unnecessary procedures more than you’ll find the cancer, Dr. Tempero said during a meeting with press at the NCCN annual conference.

Instead, it is important to identify and screen only those at high risk, she added.

Such a group might include patients with new-onset diabetes who experience weight loss.

New-onset diabetes can be caused by pancreatic cancer, and weight loss with diabetes is unexpected and should raise a red flag, Dr. Temepero explained, adding that an education gap among community physicians means these patients are sometimes cheered for the weight loss instead – and then they end up in the pancreatic disease clinic with metastatic disease 2 years later.

In an effort to better define and characterize this and other high-risk groups, the National Institute for Diabetes and Digestive and Kidney Diseases and the National Cancer Institute are working together to fund a network of institutions that will develop high-risk cohorts and begin deploying screening strategies. The effort is partly in response to the Recalcitrant Cancer Act passed in 2012 to “force more attention on funding pancreatic cancer research through the branches of the NIH,” she explained.

In this particular high-risk group, the institutions will look at the character of diabetes and the clinical correlates with pancreatic cancer.

“Once we hone in on these, we can use those – what we hope are – early-detection biomarkers, and if those are positive, then we would ask the patient to have a CT scan to look for pancreatic cancer,” she said.

Dr. Tempero reported serving as a scientific advisor and/or receiving grant/research support, consulting fees, and/or honoraria from Celgene Corporation, Champion Oncology, Cornerstone Pharmaceuticals, Eli Lilly, EMD Serono, Gilead Sciences, Halozyme Therapeutics, MCS Biotech Resources, NeoHealth, Novocure, Opsona Therapeutics, Pfizer, Portola Pharmaceuticals, and Threshold Pharmaceuticals.

[email protected]

NEW YORK – Optimal induction therapy for patients with multiple myeloma requires all the therapeutic tools currently available for combination therapy, which means using four agents followed by autologous stem cell transplantation, Paul G. Richardson, MD, said at a conference held by Imedex.

He suggested that a rational combination regimen for induction therapy of multiple myeloma would include a second- or third-generation immunomodulator such as lenalidomide (Revlimid) or pomalidomide (Pomalyst); a proteasome inhibitor such as bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro); plus standard dexamethasone to form a contemporary backbone regimen for inducing remission in patients with multiple myeloma.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

NEW YORK – Optimal induction therapy for patients with multiple myeloma requires all the therapeutic tools currently available for combination therapy, which means using four agents followed by autologous stem cell transplantation, Paul G. Richardson, MD, said at a conference held by Imedex.

He suggested that a rational combination regimen for induction therapy of multiple myeloma would include a second- or third-generation immunomodulator such as lenalidomide (Revlimid) or pomalidomide (Pomalyst); a proteasome inhibitor such as bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro); plus standard dexamethasone to form a contemporary backbone regimen for inducing remission in patients with multiple myeloma.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

NEW YORK – Optimal induction therapy for patients with multiple myeloma requires all the therapeutic tools currently available for combination therapy, which means using four agents followed by autologous stem cell transplantation, Paul G. Richardson, MD, said at a conference held by Imedex.

He suggested that a rational combination regimen for induction therapy of multiple myeloma would include a second- or third-generation immunomodulator such as lenalidomide (Revlimid) or pomalidomide (Pomalyst); a proteasome inhibitor such as bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro); plus standard dexamethasone to form a contemporary backbone regimen for inducing remission in patients with multiple myeloma.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

The Food and Drug Administration will not be able to approve a new drug application for baricitinib, a Janus kinase (JAK) inhibitor for moderate to severe rheumatoid arthritis, according to a statement from manufacturer Eli Lilly.

The FDA complete response letter cited the need for additional data to determine the most appropriate doses for the once-daily oral medication and to suss out safety concerns across treatment arms.

In the recently published RA-BEAM trial, a manufacturer-sponsored, international, randomized, double-blind, phase III clinical trial involving 1,305 adults with moderate to severe active RA, 70% of patients taking baricitinib plus background therapy with methotrexate met the primary efficacy end point – the proportion of patients at week 12 who showed an ACR 20 response – compared with 40% for placebo (N Engl J Med. 2017;376:652-62).

[email protected]

On Twitter @denisefulton

The Food and Drug Administration will not be able to approve a new drug application for baricitinib, a Janus kinase (JAK) inhibitor for moderate to severe rheumatoid arthritis, according to a statement from manufacturer Eli Lilly.

The FDA complete response letter cited the need for additional data to determine the most appropriate doses for the once-daily oral medication and to suss out safety concerns across treatment arms.

In the recently published RA-BEAM trial, a manufacturer-sponsored, international, randomized, double-blind, phase III clinical trial involving 1,305 adults with moderate to severe active RA, 70% of patients taking baricitinib plus background therapy with methotrexate met the primary efficacy end point – the proportion of patients at week 12 who showed an ACR 20 response – compared with 40% for placebo (N Engl J Med. 2017;376:652-62).

[email protected]

On Twitter @denisefulton

The Food and Drug Administration will not be able to approve a new drug application for baricitinib, a Janus kinase (JAK) inhibitor for moderate to severe rheumatoid arthritis, according to a statement from manufacturer Eli Lilly.

The FDA complete response letter cited the need for additional data to determine the most appropriate doses for the once-daily oral medication and to suss out safety concerns across treatment arms.

In the recently published RA-BEAM trial, a manufacturer-sponsored, international, randomized, double-blind, phase III clinical trial involving 1,305 adults with moderate to severe active RA, 70% of patients taking baricitinib plus background therapy with methotrexate met the primary efficacy end point – the proportion of patients at week 12 who showed an ACR 20 response – compared with 40% for placebo (N Engl J Med. 2017;376:652-62).

[email protected]

On Twitter @denisefulton

Even at the end of life, nonwhite patients with ovarian cancer are more likely to receive suboptimal care.

That’s the finding of investigators who looked at Medicare-enrolled patients with end-stage ovarian cancer in Texas. They found that compared with white patients, nonwhites were less likely to be enrolled in or die in hospice, more likely to be admitted to an intensive care unit, more likely to have an emergency department visit, and more likely to be subjected to some kind of putatively life-extending intervention.

“More investigation is needed to determine not only how to best reduce the overall number of patients with ovarian cancer who receive aggressive and invasive care but also how to lessen the disparity of who receives more aggressive and invasive care. With regard to end-of-life care for patients with ovarian cancer, less may be more,” wrote Jolyn S. Taylor, MD, MPH, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues (J Clin Oncol. 2017 April 7 doi: 10.1200/JCO.2016.70.2894).

Quality-of-care recommendations from the American Society of Clinical Oncology Quality Oncology Practice Initiative, Physician Consortium for Performance Improvement, and National Quality Forum call on clinicians to recognize that excessive or aggressive end-of-life interventions can have a negative effect on the quality of life for patients with limited life expectancy, the authors noted.

“Although changes have occurred over the last decade leading to increased hospice use by patients with ovarian cancer before death, many patients still receive intensive and invasive care in the last month of life. Similar to other disease sites, patients of minority race and ethnicity and lower socioeconomic status who have ovarian cancer have been reported to have less hospice use and more intensive end-of-life care,” the researchers wrote.

To see whether these disparities still existed, the investigators examined Texas Cancer Registry–Medicare data on patients who died from ovarian cancer from 2000 to 2012 who had least 13 months of continuous Medicare coverage before their deaths. They looked for specific measures of end-of-life care quality, including chemotherapy use within 2 weeks of death, ICU admission in the last month of life, and emergency department visits, hospital admissions, or invasive or life-extending procedures, all during the last 30 days of a patient’s life.

Of the 3,666 patients studied, 2,819 (77%) were white, 553 (15%) were Hispanic, 256 (7%) were black, and 38 (1%) were classified as “other.”

In multivariate regression models adjusted for year of death, age at death, time from diagnosis to death, Charlson comorbidity index score, disease stage at diagnosis, educational and poverty level by census tract, and geography (rural versus urban), the researchers found that both black and Hispanic patients were significantly less likely than were white patients to enroll in and die in hospice, with odds ratios (OR) of 0.66 for black patients (P = .004), and 0.76 for Hispanics (P = .01).

Black but not Hispanic patients were more likely to have had more than one emergency department visit within 30 days of death (OR 2.20, P less than .001), or a life-extending procedure (OR 2.13, P less than .001). Hispanic but not black patients were more likely to have been admitted to an ICU within a month of death (OR 1.37, P = .02).

The study was supported by grants from the Cancer Prevention & Research Institute of Texas, National Institutes of Health, National Cancer Institute, and Duncan Family Institute.

Even at the end of life, nonwhite patients with ovarian cancer are more likely to receive suboptimal care.

That’s the finding of investigators who looked at Medicare-enrolled patients with end-stage ovarian cancer in Texas. They found that compared with white patients, nonwhites were less likely to be enrolled in or die in hospice, more likely to be admitted to an intensive care unit, more likely to have an emergency department visit, and more likely to be subjected to some kind of putatively life-extending intervention.

“More investigation is needed to determine not only how to best reduce the overall number of patients with ovarian cancer who receive aggressive and invasive care but also how to lessen the disparity of who receives more aggressive and invasive care. With regard to end-of-life care for patients with ovarian cancer, less may be more,” wrote Jolyn S. Taylor, MD, MPH, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues (J Clin Oncol. 2017 April 7 doi: 10.1200/JCO.2016.70.2894).

Quality-of-care recommendations from the American Society of Clinical Oncology Quality Oncology Practice Initiative, Physician Consortium for Performance Improvement, and National Quality Forum call on clinicians to recognize that excessive or aggressive end-of-life interventions can have a negative effect on the quality of life for patients with limited life expectancy, the authors noted.

“Although changes have occurred over the last decade leading to increased hospice use by patients with ovarian cancer before death, many patients still receive intensive and invasive care in the last month of life. Similar to other disease sites, patients of minority race and ethnicity and lower socioeconomic status who have ovarian cancer have been reported to have less hospice use and more intensive end-of-life care,” the researchers wrote.

To see whether these disparities still existed, the investigators examined Texas Cancer Registry–Medicare data on patients who died from ovarian cancer from 2000 to 2012 who had least 13 months of continuous Medicare coverage before their deaths. They looked for specific measures of end-of-life care quality, including chemotherapy use within 2 weeks of death, ICU admission in the last month of life, and emergency department visits, hospital admissions, or invasive or life-extending procedures, all during the last 30 days of a patient’s life.

Of the 3,666 patients studied, 2,819 (77%) were white, 553 (15%) were Hispanic, 256 (7%) were black, and 38 (1%) were classified as “other.”

In multivariate regression models adjusted for year of death, age at death, time from diagnosis to death, Charlson comorbidity index score, disease stage at diagnosis, educational and poverty level by census tract, and geography (rural versus urban), the researchers found that both black and Hispanic patients were significantly less likely than were white patients to enroll in and die in hospice, with odds ratios (OR) of 0.66 for black patients (P = .004), and 0.76 for Hispanics (P = .01).

Black but not Hispanic patients were more likely to have had more than one emergency department visit within 30 days of death (OR 2.20, P less than .001), or a life-extending procedure (OR 2.13, P less than .001). Hispanic but not black patients were more likely to have been admitted to an ICU within a month of death (OR 1.37, P = .02).

The study was supported by grants from the Cancer Prevention & Research Institute of Texas, National Institutes of Health, National Cancer Institute, and Duncan Family Institute.

Even at the end of life, nonwhite patients with ovarian cancer are more likely to receive suboptimal care.

That’s the finding of investigators who looked at Medicare-enrolled patients with end-stage ovarian cancer in Texas. They found that compared with white patients, nonwhites were less likely to be enrolled in or die in hospice, more likely to be admitted to an intensive care unit, more likely to have an emergency department visit, and more likely to be subjected to some kind of putatively life-extending intervention.

“More investigation is needed to determine not only how to best reduce the overall number of patients with ovarian cancer who receive aggressive and invasive care but also how to lessen the disparity of who receives more aggressive and invasive care. With regard to end-of-life care for patients with ovarian cancer, less may be more,” wrote Jolyn S. Taylor, MD, MPH, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues (J Clin Oncol. 2017 April 7 doi: 10.1200/JCO.2016.70.2894).

Quality-of-care recommendations from the American Society of Clinical Oncology Quality Oncology Practice Initiative, Physician Consortium for Performance Improvement, and National Quality Forum call on clinicians to recognize that excessive or aggressive end-of-life interventions can have a negative effect on the quality of life for patients with limited life expectancy, the authors noted.

“Although changes have occurred over the last decade leading to increased hospice use by patients with ovarian cancer before death, many patients still receive intensive and invasive care in the last month of life. Similar to other disease sites, patients of minority race and ethnicity and lower socioeconomic status who have ovarian cancer have been reported to have less hospice use and more intensive end-of-life care,” the researchers wrote.

To see whether these disparities still existed, the investigators examined Texas Cancer Registry–Medicare data on patients who died from ovarian cancer from 2000 to 2012 who had least 13 months of continuous Medicare coverage before their deaths. They looked for specific measures of end-of-life care quality, including chemotherapy use within 2 weeks of death, ICU admission in the last month of life, and emergency department visits, hospital admissions, or invasive or life-extending procedures, all during the last 30 days of a patient’s life.

Of the 3,666 patients studied, 2,819 (77%) were white, 553 (15%) were Hispanic, 256 (7%) were black, and 38 (1%) were classified as “other.”

In multivariate regression models adjusted for year of death, age at death, time from diagnosis to death, Charlson comorbidity index score, disease stage at diagnosis, educational and poverty level by census tract, and geography (rural versus urban), the researchers found that both black and Hispanic patients were significantly less likely than were white patients to enroll in and die in hospice, with odds ratios (OR) of 0.66 for black patients (P = .004), and 0.76 for Hispanics (P = .01).

Black but not Hispanic patients were more likely to have had more than one emergency department visit within 30 days of death (OR 2.20, P less than .001), or a life-extending procedure (OR 2.13, P less than .001). Hispanic but not black patients were more likely to have been admitted to an ICU within a month of death (OR 1.37, P = .02).

The study was supported by grants from the Cancer Prevention & Research Institute of Texas, National Institutes of Health, National Cancer Institute, and Duncan Family Institute.

BOSTON – Two gastroenterology innovators spoke at the 2017 AGA Tech Summit, which is sponsored by the AGA Center for Innovation and Technology, to share how their past participation in the AGA Shark Tank panel is helping them succeed.

Single-use endoscopes

For Invendo Medical GmbH Chief Commercial Officer John Cifarelli, who appeared before the panel during the 2015 Tech Summit, having Shark Tank experts suggest that he and his collaborators keep in mind physician practice habits when bringing their single-use endoscope technology to market was key to their ultimate product designs.

Rather than create a separate, stand-alone, hand-held device as planned, Invendo instead is manufacturing the Invendoscope^TM, a hand-held, HD optics, sterile, single-use device that can be used either attached to or detached from the endoscope – the first such device of its kind, he said. The Invendoscope recently received its CE mark and is expected to come to market later this year.

Mr. Cifarelli said his company is also at work on an HD, single-use, sterile gastroscope and duodenoscope, both of which he expects will be introduced by early 2018.

Technology IDs progression risk in Barrett’s

Appearing before the 2015 panel gave Cernostics CEO Mike Hoerres a comprehensive perspective that subsequently has served his collaborators and him well. The company was just issued two patents on the TissueCypher^TM Image Analysis Platform, a tissue systems biology approach that evaluates protein expression in the context of tissue structure when analyzing biopsies from patients with Barrett’s esophagus. The assay technology simultaneously and objectively extracts high-dimensional biomarker expression and morphology data to evaluate multiple tumor, immune, and other stromal processes in a single tissue section.

[email protected]

On Twitter @whitneymcknight

BOSTON – Two gastroenterology innovators spoke at the 2017 AGA Tech Summit, which is sponsored by the AGA Center for Innovation and Technology, to share how their past participation in the AGA Shark Tank panel is helping them succeed.

Single-use endoscopes

For Invendo Medical GmbH Chief Commercial Officer John Cifarelli, who appeared before the panel during the 2015 Tech Summit, having Shark Tank experts suggest that he and his collaborators keep in mind physician practice habits when bringing their single-use endoscope technology to market was key to their ultimate product designs.

Rather than create a separate, stand-alone, hand-held device as planned, Invendo instead is manufacturing the Invendoscope^TM, a hand-held, HD optics, sterile, single-use device that can be used either attached to or detached from the endoscope – the first such device of its kind, he said. The Invendoscope recently received its CE mark and is expected to come to market later this year.

Mr. Cifarelli said his company is also at work on an HD, single-use, sterile gastroscope and duodenoscope, both of which he expects will be introduced by early 2018.

Technology IDs progression risk in Barrett’s

Appearing before the 2015 panel gave Cernostics CEO Mike Hoerres a comprehensive perspective that subsequently has served his collaborators and him well. The company was just issued two patents on the TissueCypher^TM Image Analysis Platform, a tissue systems biology approach that evaluates protein expression in the context of tissue structure when analyzing biopsies from patients with Barrett’s esophagus. The assay technology simultaneously and objectively extracts high-dimensional biomarker expression and morphology data to evaluate multiple tumor, immune, and other stromal processes in a single tissue section.

[email protected]

On Twitter @whitneymcknight

BOSTON – Two gastroenterology innovators spoke at the 2017 AGA Tech Summit, which is sponsored by the AGA Center for Innovation and Technology, to share how their past participation in the AGA Shark Tank panel is helping them succeed.

Single-use endoscopes

For Invendo Medical GmbH Chief Commercial Officer John Cifarelli, who appeared before the panel during the 2015 Tech Summit, having Shark Tank experts suggest that he and his collaborators keep in mind physician practice habits when bringing their single-use endoscope technology to market was key to their ultimate product designs.

Rather than create a separate, stand-alone, hand-held device as planned, Invendo instead is manufacturing the Invendoscope^TM, a hand-held, HD optics, sterile, single-use device that can be used either attached to or detached from the endoscope – the first such device of its kind, he said. The Invendoscope recently received its CE mark and is expected to come to market later this year.

Mr. Cifarelli said his company is also at work on an HD, single-use, sterile gastroscope and duodenoscope, both of which he expects will be introduced by early 2018.

Technology IDs progression risk in Barrett’s

Appearing before the 2015 panel gave Cernostics CEO Mike Hoerres a comprehensive perspective that subsequently has served his collaborators and him well. The company was just issued two patents on the TissueCypher^TM Image Analysis Platform, a tissue systems biology approach that evaluates protein expression in the context of tissue structure when analyzing biopsies from patients with Barrett’s esophagus. The assay technology simultaneously and objectively extracts high-dimensional biomarker expression and morphology data to evaluate multiple tumor, immune, and other stromal processes in a single tissue section.

[email protected]

On Twitter @whitneymcknight

Extended follow-up of postmenopausal women taking denosumab for high-risk osteoporosis in the FREEDOM trial showed no increasing rates of either common adverse events or specific adverse events identified in the original study.

“This analysis provides reassuring information regarding safety and tolerability of both short-term and longer-term treatment with denosumab,” said Nelson B. Watts, MD, of Mercy Health, Cincinnati, and his associates.

Extended follow-up of postmenopausal women taking denosumab for high-risk osteoporosis in the FREEDOM trial showed no increasing rates of either common adverse events or specific adverse events identified in the original study.

“This analysis provides reassuring information regarding safety and tolerability of both short-term and longer-term treatment with denosumab,” said Nelson B. Watts, MD, of Mercy Health, Cincinnati, and his associates.

Extended follow-up of postmenopausal women taking denosumab for high-risk osteoporosis in the FREEDOM trial showed no increasing rates of either common adverse events or specific adverse events identified in the original study.

“This analysis provides reassuring information regarding safety and tolerability of both short-term and longer-term treatment with denosumab,” said Nelson B. Watts, MD, of Mercy Health, Cincinnati, and his associates.

ORLANDO – A novel antagonist of a neurokinin pathway effectively reduced hot flashes in postmenopausal women, according to results of a phase II trial.

The neurokinin 3 receptor (NK3R) antagonist, termed MLE4901, cut the number of hot flashes nearly in half compared to the effect of a placebo, and also improved overall menopause-related quality of life symptoms.

The medication has the potential to fulfill an unmet clinical need, since 70% of women experience hot flashes and the median duration of symptoms is more than 7 years, Julia K. Prague, MD, said at the annual meeting of the Endocrine Society.

The study results were published concurrently with Dr. Prague’s presentation (Lancet. 2017 Apr 3. doi: 10.1016/S0140-6736[17]30823-1).

Evidence from postmortem studies of postmenopausal women, said Dr. Prague, pointed to NKB (neurokinin B)/NK3R signaling as playing a role in hot flashes. The brains of these women showed hypertrophy of NKB neurons and increased neuronal activity, as well as increased NKB gene expression. The same effects were seen in monkeys whose ovaries had been removed, and the effect was reversed when the monkeys were given estrogen.

BakiBG/Thinkstock

The study was supported by AstraZeneca and Millendo Therapeutics, which are involved with manufacturing MLE4901.

[email protected]

On Twitter @karioakes

ORLANDO – A novel antagonist of a neurokinin pathway effectively reduced hot flashes in postmenopausal women, according to results of a phase II trial.

The neurokinin 3 receptor (NK3R) antagonist, termed MLE4901, cut the number of hot flashes nearly in half compared to the effect of a placebo, and also improved overall menopause-related quality of life symptoms.

The medication has the potential to fulfill an unmet clinical need, since 70% of women experience hot flashes and the median duration of symptoms is more than 7 years, Julia K. Prague, MD, said at the annual meeting of the Endocrine Society.

The study results were published concurrently with Dr. Prague’s presentation (Lancet. 2017 Apr 3. doi: 10.1016/S0140-6736[17]30823-1).

Evidence from postmortem studies of postmenopausal women, said Dr. Prague, pointed to NKB (neurokinin B)/NK3R signaling as playing a role in hot flashes. The brains of these women showed hypertrophy of NKB neurons and increased neuronal activity, as well as increased NKB gene expression. The same effects were seen in monkeys whose ovaries had been removed, and the effect was reversed when the monkeys were given estrogen.

BakiBG/Thinkstock

The study was supported by AstraZeneca and Millendo Therapeutics, which are involved with manufacturing MLE4901.

[email protected]

On Twitter @karioakes

ORLANDO – A novel antagonist of a neurokinin pathway effectively reduced hot flashes in postmenopausal women, according to results of a phase II trial.

The neurokinin 3 receptor (NK3R) antagonist, termed MLE4901, cut the number of hot flashes nearly in half compared to the effect of a placebo, and also improved overall menopause-related quality of life symptoms.

The medication has the potential to fulfill an unmet clinical need, since 70% of women experience hot flashes and the median duration of symptoms is more than 7 years, Julia K. Prague, MD, said at the annual meeting of the Endocrine Society.

The study results were published concurrently with Dr. Prague’s presentation (Lancet. 2017 Apr 3. doi: 10.1016/S0140-6736[17]30823-1).

Evidence from postmortem studies of postmenopausal women, said Dr. Prague, pointed to NKB (neurokinin B)/NK3R signaling as playing a role in hot flashes. The brains of these women showed hypertrophy of NKB neurons and increased neuronal activity, as well as increased NKB gene expression. The same effects were seen in monkeys whose ovaries had been removed, and the effect was reversed when the monkeys were given estrogen.

BakiBG/Thinkstock

The study was supported by AstraZeneca and Millendo Therapeutics, which are involved with manufacturing MLE4901.

[email protected]

On Twitter @karioakes

HOUSTON – Selected patients who need operations, such as paraesophageal hernia repair and Heller myotomy, for benign hiatal diseases can have laparoscopic outpatient procedures with outcomes comparable with those of inpatients, a Canadian retrospective cohort study found.

“When comparing planned day-case patients with those who had planned admissions, we found that postoperative complication was the only statistically significant different outcome. Our data show same-day discharge resulted in no postoperative mortality, and no difference in postoperative morbidity, emergency room visits, and readmissions compared to traditional inpatient care,” said Juan Carlos Molina, MD, of McGill University Health Centre in Montreal, reporting the study results at the annual meeting of the American Society of Gastrointestinal and Endoscopic Surgeons.

HOUSTON – Selected patients who need operations, such as paraesophageal hernia repair and Heller myotomy, for benign hiatal diseases can have laparoscopic outpatient procedures with outcomes comparable with those of inpatients, a Canadian retrospective cohort study found.

“When comparing planned day-case patients with those who had planned admissions, we found that postoperative complication was the only statistically significant different outcome. Our data show same-day discharge resulted in no postoperative mortality, and no difference in postoperative morbidity, emergency room visits, and readmissions compared to traditional inpatient care,” said Juan Carlos Molina, MD, of McGill University Health Centre in Montreal, reporting the study results at the annual meeting of the American Society of Gastrointestinal and Endoscopic Surgeons.

HOUSTON – Selected patients who need operations, such as paraesophageal hernia repair and Heller myotomy, for benign hiatal diseases can have laparoscopic outpatient procedures with outcomes comparable with those of inpatients, a Canadian retrospective cohort study found.

“When comparing planned day-case patients with those who had planned admissions, we found that postoperative complication was the only statistically significant different outcome. Our data show same-day discharge resulted in no postoperative mortality, and no difference in postoperative morbidity, emergency room visits, and readmissions compared to traditional inpatient care,” said Juan Carlos Molina, MD, of McGill University Health Centre in Montreal, reporting the study results at the annual meeting of the American Society of Gastrointestinal and Endoscopic Surgeons.

BOSTON – A lot has changed in GI technology since V. Raman Muthusamy, MD, the incoming chair of the AGA Center for GI Innovation and Technology(CGIT), completed his GI fellowship training 15 years ago.

“I would say that between half and two-thirds of what I do today for actual patient care delivery is from technologies that have been completed since my fellowship or [from] applications of those technologies that are new,” he said in a video interview conducted during the 2017 AGA Technology Summit, which is sponsored by the center. So if you think you’re not impacted by innovation, think again.

“I think like many practicing physicians we have great technology, but we can think of ways to do things better,” continued Dr. Muthusamy, professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles.

One of the goals of the center is to streamline the process of taking a good idea and making it into a product and a company. Dr. Muthusamy said such streamlining is important because the current “daunting” development process has led to many good ideas “dying on the vine” before they could be implemented. He says the CGIT, by bringing together key stakeholders from the medical, business, and regulatory arenas, can help bring forth the latest technologies to directly benefit GI patients.

[email protected]

BOSTON – A lot has changed in GI technology since V. Raman Muthusamy, MD, the incoming chair of the AGA Center for GI Innovation and Technology(CGIT), completed his GI fellowship training 15 years ago.

“I would say that between half and two-thirds of what I do today for actual patient care delivery is from technologies that have been completed since my fellowship or [from] applications of those technologies that are new,” he said in a video interview conducted during the 2017 AGA Technology Summit, which is sponsored by the center. So if you think you’re not impacted by innovation, think again.

“I think like many practicing physicians we have great technology, but we can think of ways to do things better,” continued Dr. Muthusamy, professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles.

One of the goals of the center is to streamline the process of taking a good idea and making it into a product and a company. Dr. Muthusamy said such streamlining is important because the current “daunting” development process has led to many good ideas “dying on the vine” before they could be implemented. He says the CGIT, by bringing together key stakeholders from the medical, business, and regulatory arenas, can help bring forth the latest technologies to directly benefit GI patients.

[email protected]

BOSTON – A lot has changed in GI technology since V. Raman Muthusamy, MD, the incoming chair of the AGA Center for GI Innovation and Technology(CGIT), completed his GI fellowship training 15 years ago.

“I would say that between half and two-thirds of what I do today for actual patient care delivery is from technologies that have been completed since my fellowship or [from] applications of those technologies that are new,” he said in a video interview conducted during the 2017 AGA Technology Summit, which is sponsored by the center. So if you think you’re not impacted by innovation, think again.

“I think like many practicing physicians we have great technology, but we can think of ways to do things better,” continued Dr. Muthusamy, professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles.

One of the goals of the center is to streamline the process of taking a good idea and making it into a product and a company. Dr. Muthusamy said such streamlining is important because the current “daunting” development process has led to many good ideas “dying on the vine” before they could be implemented. He says the CGIT, by bringing together key stakeholders from the medical, business, and regulatory arenas, can help bring forth the latest technologies to directly benefit GI patients.

[email protected]