Key clinical point: The addition of oral alisertib to a reduced dose of weekly paclitaxel improves progression-free survival (PFS) compared with paclitaxel alone in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer.

Major finding: At a median follow-up of 22 months, the median PFS was 10.2 months with paclitaxel plus alisertib vs. 7.1 months with paclitaxel alone (hazard ratio, 0.56; P = .005) in the patients with ER+, HER2-negative disease. Grade 3-4 adverse event rate was higher with paclitaxel plus alisertib vs. paclitaxel alone (84.8% vs. 48.6%).

Study details: A phase 2, open-label, randomized study of 139 patients with metastatic breast cancer who received either paclitaxel or paclitaxel plus alisertib.

Disclosures: The study was supported by a research grant from Takeda Pharmaceuticals. Dr. O’Shaughnessy and Dr. Andorsky declared receiving personal fees, consulting and/or serving on steering committee meetings for various sources.

Source: O'Shaughnessy J et al. JAMA Netw Open. 2021 Apr 20. doi: 10.1001/jamanetworkopen.2021.4103.

Key clinical point: The addition of oral alisertib to a reduced dose of weekly paclitaxel improves progression-free survival (PFS) compared with paclitaxel alone in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer.

Major finding: At a median follow-up of 22 months, the median PFS was 10.2 months with paclitaxel plus alisertib vs. 7.1 months with paclitaxel alone (hazard ratio, 0.56; P = .005) in the patients with ER+, HER2-negative disease. Grade 3-4 adverse event rate was higher with paclitaxel plus alisertib vs. paclitaxel alone (84.8% vs. 48.6%).

Study details: A phase 2, open-label, randomized study of 139 patients with metastatic breast cancer who received either paclitaxel or paclitaxel plus alisertib.

Disclosures: The study was supported by a research grant from Takeda Pharmaceuticals. Dr. O’Shaughnessy and Dr. Andorsky declared receiving personal fees, consulting and/or serving on steering committee meetings for various sources.

Source: O'Shaughnessy J et al. JAMA Netw Open. 2021 Apr 20. doi: 10.1001/jamanetworkopen.2021.4103.

Key clinical point: The addition of oral alisertib to a reduced dose of weekly paclitaxel improves progression-free survival (PFS) compared with paclitaxel alone in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer.

Major finding: At a median follow-up of 22 months, the median PFS was 10.2 months with paclitaxel plus alisertib vs. 7.1 months with paclitaxel alone (hazard ratio, 0.56; P = .005) in the patients with ER+, HER2-negative disease. Grade 3-4 adverse event rate was higher with paclitaxel plus alisertib vs. paclitaxel alone (84.8% vs. 48.6%).

Study details: A phase 2, open-label, randomized study of 139 patients with metastatic breast cancer who received either paclitaxel or paclitaxel plus alisertib.

Disclosures: The study was supported by a research grant from Takeda Pharmaceuticals. Dr. O’Shaughnessy and Dr. Andorsky declared receiving personal fees, consulting and/or serving on steering committee meetings for various sources.

Source: O'Shaughnessy J et al. JAMA Netw Open. 2021 Apr 20. doi: 10.1001/jamanetworkopen.2021.4103.

Two more cancer indications that had been granted accelerated approval by the Food and Drug Administration are going to stay in place, at least for now. This was the verdict after the second day of a historic 3-day meeting (April 27-29) and follows a similar verdict from day 1.

Federal advisers so far have supported the idea of maintaining conditional approvals of some cancer indications for a number of immune checkpoint inhibitors, despite poor results in studies that were meant to confirm the benefit of these medicines for certain patients.

On the second day (April 28) of the FDA meeting, the Oncologic Drugs Advisory Committee (ODAC) supported the views of pharmaceutical companies in two more cases of what top agency staff call “dangling accelerated approvals.”

ODAC voted 10-1 in favor of maintaining the indication for atezolizumab (Tecentriq) for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

ODAC also voted 5-3 that day in favor of maintaining accelerated approval for pembrolizumab (Keytruda) for first-line cisplatin- and carboplatin-ineligible patients with advanced/metastatic urothelial carcinoma.

The FDA often follows the advice of its panels, but it is not bound to do so. If the FDA were to decide to strip the indications in question from these PD-1 medicines, such decisions would not remove these drugs from the market. The three drugs have already been approved for a number of other cancer indications.

Off-label prescribing is not uncommon in oncology, but a loss of an approved indication would affect reimbursement for these medicines, Scot Ebbinghaus, MD, vice president of oncology clinical research at Merck (the manufacturer of pembrolizumab), told ODAC members during a discussion of the possible consequences of removing the indications in question.

“Access to those treatments may end up being substantially limited, and really the best way to ensure that there’s access is to maintain FDA approval,” Dr. Ebbinghaus said.

Another participant at the meeting asked the panel and the FDA to consider the burden on patients in paying for medicines that have not yet proved to be beneficial.

Diana Zuckerman, PhD, of the nonprofit National Center for Health Research, noted that the ODAC panel included physicians who see cancer patients.

“You’re used to trying different types of treatments in hopes that something will work,” she said. “Shouldn’t cancer patients be eligible for free treatment in clinical trials instead of paying for treatment that isn’t proven to work?”

Rapid development of PD-1 drugs

Top officials at the FDA framed the challenges with accelerated approvals for immunotherapy drugs in an April 21 article in The New England Journal of Medicine. Over the course of about 6 years, the FDA approved six of these PD-1 or PD-L1 drugs for more than 75 indications in oncology, wrote Richard Pazdur, MD, and Julia A. Beaver, MD, of the FDA.

“Development of drugs in this class occurred more rapidly than that in any other therapeutic area in history,” they wrote.

In 10 cases, the required follow-up trials did not confirm the expected benefit, and yet marketing authorization for these drugs continued, leading Dr. Pazdur and Dr. Beaver to dub these “dangling” accelerated approvals. Four of these indications were voluntarily withdrawn. For the other six indications, the FDA sought feedback from ODAC during the 3-day meeting. Over the first 2 days of the meeting, ODAC recommended that three of these cancer indications remain. Three more will be considered on the last day of the meeting.

A version of this article first appeared on Medscape.com.

Two more cancer indications that had been granted accelerated approval by the Food and Drug Administration are going to stay in place, at least for now. This was the verdict after the second day of a historic 3-day meeting (April 27-29) and follows a similar verdict from day 1.

Federal advisers so far have supported the idea of maintaining conditional approvals of some cancer indications for a number of immune checkpoint inhibitors, despite poor results in studies that were meant to confirm the benefit of these medicines for certain patients.

On the second day (April 28) of the FDA meeting, the Oncologic Drugs Advisory Committee (ODAC) supported the views of pharmaceutical companies in two more cases of what top agency staff call “dangling accelerated approvals.”

ODAC voted 10-1 in favor of maintaining the indication for atezolizumab (Tecentriq) for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

ODAC also voted 5-3 that day in favor of maintaining accelerated approval for pembrolizumab (Keytruda) for first-line cisplatin- and carboplatin-ineligible patients with advanced/metastatic urothelial carcinoma.

The FDA often follows the advice of its panels, but it is not bound to do so. If the FDA were to decide to strip the indications in question from these PD-1 medicines, such decisions would not remove these drugs from the market. The three drugs have already been approved for a number of other cancer indications.

Off-label prescribing is not uncommon in oncology, but a loss of an approved indication would affect reimbursement for these medicines, Scot Ebbinghaus, MD, vice president of oncology clinical research at Merck (the manufacturer of pembrolizumab), told ODAC members during a discussion of the possible consequences of removing the indications in question.

“Access to those treatments may end up being substantially limited, and really the best way to ensure that there’s access is to maintain FDA approval,” Dr. Ebbinghaus said.

Another participant at the meeting asked the panel and the FDA to consider the burden on patients in paying for medicines that have not yet proved to be beneficial.

Diana Zuckerman, PhD, of the nonprofit National Center for Health Research, noted that the ODAC panel included physicians who see cancer patients.

“You’re used to trying different types of treatments in hopes that something will work,” she said. “Shouldn’t cancer patients be eligible for free treatment in clinical trials instead of paying for treatment that isn’t proven to work?”

Rapid development of PD-1 drugs

Top officials at the FDA framed the challenges with accelerated approvals for immunotherapy drugs in an April 21 article in The New England Journal of Medicine. Over the course of about 6 years, the FDA approved six of these PD-1 or PD-L1 drugs for more than 75 indications in oncology, wrote Richard Pazdur, MD, and Julia A. Beaver, MD, of the FDA.

“Development of drugs in this class occurred more rapidly than that in any other therapeutic area in history,” they wrote.

In 10 cases, the required follow-up trials did not confirm the expected benefit, and yet marketing authorization for these drugs continued, leading Dr. Pazdur and Dr. Beaver to dub these “dangling” accelerated approvals. Four of these indications were voluntarily withdrawn. For the other six indications, the FDA sought feedback from ODAC during the 3-day meeting. Over the first 2 days of the meeting, ODAC recommended that three of these cancer indications remain. Three more will be considered on the last day of the meeting.

A version of this article first appeared on Medscape.com.

Two more cancer indications that had been granted accelerated approval by the Food and Drug Administration are going to stay in place, at least for now. This was the verdict after the second day of a historic 3-day meeting (April 27-29) and follows a similar verdict from day 1.

Federal advisers so far have supported the idea of maintaining conditional approvals of some cancer indications for a number of immune checkpoint inhibitors, despite poor results in studies that were meant to confirm the benefit of these medicines for certain patients.

On the second day (April 28) of the FDA meeting, the Oncologic Drugs Advisory Committee (ODAC) supported the views of pharmaceutical companies in two more cases of what top agency staff call “dangling accelerated approvals.”

ODAC voted 10-1 in favor of maintaining the indication for atezolizumab (Tecentriq) for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

ODAC also voted 5-3 that day in favor of maintaining accelerated approval for pembrolizumab (Keytruda) for first-line cisplatin- and carboplatin-ineligible patients with advanced/metastatic urothelial carcinoma.

The FDA often follows the advice of its panels, but it is not bound to do so. If the FDA were to decide to strip the indications in question from these PD-1 medicines, such decisions would not remove these drugs from the market. The three drugs have already been approved for a number of other cancer indications.

Off-label prescribing is not uncommon in oncology, but a loss of an approved indication would affect reimbursement for these medicines, Scot Ebbinghaus, MD, vice president of oncology clinical research at Merck (the manufacturer of pembrolizumab), told ODAC members during a discussion of the possible consequences of removing the indications in question.

“Access to those treatments may end up being substantially limited, and really the best way to ensure that there’s access is to maintain FDA approval,” Dr. Ebbinghaus said.

Another participant at the meeting asked the panel and the FDA to consider the burden on patients in paying for medicines that have not yet proved to be beneficial.

Diana Zuckerman, PhD, of the nonprofit National Center for Health Research, noted that the ODAC panel included physicians who see cancer patients.

“You’re used to trying different types of treatments in hopes that something will work,” she said. “Shouldn’t cancer patients be eligible for free treatment in clinical trials instead of paying for treatment that isn’t proven to work?”

Rapid development of PD-1 drugs

Top officials at the FDA framed the challenges with accelerated approvals for immunotherapy drugs in an April 21 article in The New England Journal of Medicine. Over the course of about 6 years, the FDA approved six of these PD-1 or PD-L1 drugs for more than 75 indications in oncology, wrote Richard Pazdur, MD, and Julia A. Beaver, MD, of the FDA.

“Development of drugs in this class occurred more rapidly than that in any other therapeutic area in history,” they wrote.

In 10 cases, the required follow-up trials did not confirm the expected benefit, and yet marketing authorization for these drugs continued, leading Dr. Pazdur and Dr. Beaver to dub these “dangling” accelerated approvals. Four of these indications were voluntarily withdrawn. For the other six indications, the FDA sought feedback from ODAC during the 3-day meeting. Over the first 2 days of the meeting, ODAC recommended that three of these cancer indications remain. Three more will be considered on the last day of the meeting.

A version of this article first appeared on Medscape.com.

Key clinical point: The detrimental effects of chemotherapy on quality of life (QoL) are significant at 12 months in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with either chemotherapy plus trastuzumab vs. trastuzumab monotherapy. There was no difference in QoL after 36 months between treatments.

Major finding: At 12 months, the proportion of patients showing QoL deterioration was significantly lower in the trastuzumab monotherapy vs. trastuzumab plus chemotherapy group (19% vs. 38%; P = .009). A significantly higher number of patients showed improvement in QoL with trastuzumab monotherapy at 12 months (43% vs. 25%; P = .021). No difference was reported in any QoL items at 36 months between the 2 treatment groups.

Study details: The QoL analysis of phase 3, randomized RESPECT trial included 231 older patients with HER2-positive breast cancer who received either trastuzumab monotherapy (mean age, 73.9 years) or trastuzumab plus chemotherapy (mean age, 73.7 years).

Disclosures: The analysis was supported by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan. The authors received consulting fees, honoraria, and research funding outside this work.

Source: Taira N et al. J Clin Oncol. 2021 Apr 9. doi: 10.1200/JCO.20.02751.

Key clinical point: The detrimental effects of chemotherapy on quality of life (QoL) are significant at 12 months in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with either chemotherapy plus trastuzumab vs. trastuzumab monotherapy. There was no difference in QoL after 36 months between treatments.

Major finding: At 12 months, the proportion of patients showing QoL deterioration was significantly lower in the trastuzumab monotherapy vs. trastuzumab plus chemotherapy group (19% vs. 38%; P = .009). A significantly higher number of patients showed improvement in QoL with trastuzumab monotherapy at 12 months (43% vs. 25%; P = .021). No difference was reported in any QoL items at 36 months between the 2 treatment groups.

Study details: The QoL analysis of phase 3, randomized RESPECT trial included 231 older patients with HER2-positive breast cancer who received either trastuzumab monotherapy (mean age, 73.9 years) or trastuzumab plus chemotherapy (mean age, 73.7 years).

Disclosures: The analysis was supported by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan. The authors received consulting fees, honoraria, and research funding outside this work.

Source: Taira N et al. J Clin Oncol. 2021 Apr 9. doi: 10.1200/JCO.20.02751.

Key clinical point: The detrimental effects of chemotherapy on quality of life (QoL) are significant at 12 months in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with either chemotherapy plus trastuzumab vs. trastuzumab monotherapy. There was no difference in QoL after 36 months between treatments.

Major finding: At 12 months, the proportion of patients showing QoL deterioration was significantly lower in the trastuzumab monotherapy vs. trastuzumab plus chemotherapy group (19% vs. 38%; P = .009). A significantly higher number of patients showed improvement in QoL with trastuzumab monotherapy at 12 months (43% vs. 25%; P = .021). No difference was reported in any QoL items at 36 months between the 2 treatment groups.

Study details: The QoL analysis of phase 3, randomized RESPECT trial included 231 older patients with HER2-positive breast cancer who received either trastuzumab monotherapy (mean age, 73.9 years) or trastuzumab plus chemotherapy (mean age, 73.7 years).

Disclosures: The analysis was supported by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan. The authors received consulting fees, honoraria, and research funding outside this work.

Source: Taira N et al. J Clin Oncol. 2021 Apr 9. doi: 10.1200/JCO.20.02751.

Key clinical point: Pembrolizumab plus eribulin shows activity in patients with heavily pretreated, hormone-receptor–positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative, locally recurrent, or metastatic breast cancer.

Major finding: The clinical benefit rate was 56.8%, and the objective response rate was 40.9%. The median progression-free survival was 6.0 months. The serious adverse event rate was 31.8%, and 25.0% of patients experienced immune-related adverse events.

Study details: Phase 2 study of 44 previously treated patients with HR+, HER-negative, inoperable, locally recurrent breast cancer received pembrolizumab plus eribulin.

Disclosures: The study was supported by MSD Spain. Some of the authors declared receiving consulting fees, honoraria, travel expenses and/or research funding from various sources.

Source: Pérez-García JM et al. Eur J Cancer. 2021 Mar 29. doi: 10.1016/j.ejca.2021.02.028.

Key clinical point: Pembrolizumab plus eribulin shows activity in patients with heavily pretreated, hormone-receptor–positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative, locally recurrent, or metastatic breast cancer.

Major finding: The clinical benefit rate was 56.8%, and the objective response rate was 40.9%. The median progression-free survival was 6.0 months. The serious adverse event rate was 31.8%, and 25.0% of patients experienced immune-related adverse events.

Study details: Phase 2 study of 44 previously treated patients with HR+, HER-negative, inoperable, locally recurrent breast cancer received pembrolizumab plus eribulin.

Disclosures: The study was supported by MSD Spain. Some of the authors declared receiving consulting fees, honoraria, travel expenses and/or research funding from various sources.

Source: Pérez-García JM et al. Eur J Cancer. 2021 Mar 29. doi: 10.1016/j.ejca.2021.02.028.

Key clinical point: Pembrolizumab plus eribulin shows activity in patients with heavily pretreated, hormone-receptor–positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative, locally recurrent, or metastatic breast cancer.

Major finding: The clinical benefit rate was 56.8%, and the objective response rate was 40.9%. The median progression-free survival was 6.0 months. The serious adverse event rate was 31.8%, and 25.0% of patients experienced immune-related adverse events.

Study details: Phase 2 study of 44 previously treated patients with HR+, HER-negative, inoperable, locally recurrent breast cancer received pembrolizumab plus eribulin.

Disclosures: The study was supported by MSD Spain. Some of the authors declared receiving consulting fees, honoraria, travel expenses and/or research funding from various sources.

Source: Pérez-García JM et al. Eur J Cancer. 2021 Mar 29. doi: 10.1016/j.ejca.2021.02.028.

Key clinical point: Long-term data show similar local control rates with 10-Gy intraoperative electron radiotherapy (IOERT) vs. external beam radiotherapy (EBRT).

Major finding: The cumulative risk for in-breast true recurrences at 10 years was 4.3% after IOERT vs. 5.3% after EBRT boost (P = .493). The cumulative risk for out-field local recurrence at 10 years was 7.9% for IOERT vs. 10.3% for EBRT (P = .611).

Study details: Phase 3 randomized study of 245 patients with early-stage breast cancer who underwent breast-conserving surgery with either 10-Gy IOERT or EBRT boost.

Disclosures: An author received a study grant from IntraOp Medical. The authors declared no conflict of interests.

Source: Ciabattoni A et al. Breast Can Res. 2021 Apr 13. doi: 10.1186/s13058-021-01424-9.

Key clinical point: Long-term data show similar local control rates with 10-Gy intraoperative electron radiotherapy (IOERT) vs. external beam radiotherapy (EBRT).

Major finding: The cumulative risk for in-breast true recurrences at 10 years was 4.3% after IOERT vs. 5.3% after EBRT boost (P = .493). The cumulative risk for out-field local recurrence at 10 years was 7.9% for IOERT vs. 10.3% for EBRT (P = .611).

Study details: Phase 3 randomized study of 245 patients with early-stage breast cancer who underwent breast-conserving surgery with either 10-Gy IOERT or EBRT boost.

Disclosures: An author received a study grant from IntraOp Medical. The authors declared no conflict of interests.

Source: Ciabattoni A et al. Breast Can Res. 2021 Apr 13. doi: 10.1186/s13058-021-01424-9.

Key clinical point: Long-term data show similar local control rates with 10-Gy intraoperative electron radiotherapy (IOERT) vs. external beam radiotherapy (EBRT).

Major finding: The cumulative risk for in-breast true recurrences at 10 years was 4.3% after IOERT vs. 5.3% after EBRT boost (P = .493). The cumulative risk for out-field local recurrence at 10 years was 7.9% for IOERT vs. 10.3% for EBRT (P = .611).

Study details: Phase 3 randomized study of 245 patients with early-stage breast cancer who underwent breast-conserving surgery with either 10-Gy IOERT or EBRT boost.

Disclosures: An author received a study grant from IntraOp Medical. The authors declared no conflict of interests.

Source: Ciabattoni A et al. Breast Can Res. 2021 Apr 13. doi: 10.1186/s13058-021-01424-9.

Key clinical point: Sacituzumab govitecan improves survival vs. single-agent chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).

Major finding: Sacituzumab govitecan vs. chemotherapy showed 59% and 52% reduction in the risk for progression and mortality, respectively (P less than .001 for both). The objective response rate was 35% with sacituzumab govitecan and 5% with chemotherapy. Grade 3-4 adverse event rate was 64% and 47% in the sacituzumab govitecan and chemotherapy groups, respectively.

Study details: A phase 3 ASCENT study of patients with relapsed or refractory TNBC, randomly assigned to receive either sacituzumab govitecan or single-agent chemotherapy of physician’s choice.

Disclosures: The study was supported by Immunomedics, a subsidiary of Gilead Sciences. The authors received consulting fees outside this work.

Source: Bardia A et al. New Eng J Med. 2021 Apr 22. doi: 10.1056/NEJMoa2028485.

Key clinical point: Sacituzumab govitecan improves survival vs. single-agent chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).

Major finding: Sacituzumab govitecan vs. chemotherapy showed 59% and 52% reduction in the risk for progression and mortality, respectively (P less than .001 for both). The objective response rate was 35% with sacituzumab govitecan and 5% with chemotherapy. Grade 3-4 adverse event rate was 64% and 47% in the sacituzumab govitecan and chemotherapy groups, respectively.

Study details: A phase 3 ASCENT study of patients with relapsed or refractory TNBC, randomly assigned to receive either sacituzumab govitecan or single-agent chemotherapy of physician’s choice.

Disclosures: The study was supported by Immunomedics, a subsidiary of Gilead Sciences. The authors received consulting fees outside this work.

Source: Bardia A et al. New Eng J Med. 2021 Apr 22. doi: 10.1056/NEJMoa2028485.

Key clinical point: Sacituzumab govitecan improves survival vs. single-agent chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).

Major finding: Sacituzumab govitecan vs. chemotherapy showed 59% and 52% reduction in the risk for progression and mortality, respectively (P less than .001 for both). The objective response rate was 35% with sacituzumab govitecan and 5% with chemotherapy. Grade 3-4 adverse event rate was 64% and 47% in the sacituzumab govitecan and chemotherapy groups, respectively.

Study details: A phase 3 ASCENT study of patients with relapsed or refractory TNBC, randomly assigned to receive either sacituzumab govitecan or single-agent chemotherapy of physician’s choice.

Disclosures: The study was supported by Immunomedics, a subsidiary of Gilead Sciences. The authors received consulting fees outside this work.

Source: Bardia A et al. New Eng J Med. 2021 Apr 22. doi: 10.1056/NEJMoa2028485.

Key clinical point: The clinical presentation of exocrine pancreatic insufficiency (EPI) is probably mild in the early postoperative period following gastric resectional surgery. Thus, routine pancreatic supplementation may not be needed after surgery; however, worsening of EPI symptoms should be carefully monitored.

Major finding: During a mean follow-up of 3 months, none of the patients developed clinically significant steatorrhoea or fat malabsorption in postoperative setting. Incidence of EPI (fecal elastase less than 200 μg/g) following gastric resectional surgery was 33.3%.

Study details: This prospective study included 60 patients who received total or subtotal gastrectomy for adenocarcinoma of the stomach. Pre- and postoperative FE testing was done in 27 patients.

Disclosures: This study was funded by the Internal Fluid research Grant, Christian Medical College, Vellore, India. The authors declared no conflicts of interest.

Source: Sridhar RP et al. Indian J Surg Oncol. 2021 Apr 5. doi: 10.1007/s13193-021-01315-7.

Key clinical point: The clinical presentation of exocrine pancreatic insufficiency (EPI) is probably mild in the early postoperative period following gastric resectional surgery. Thus, routine pancreatic supplementation may not be needed after surgery; however, worsening of EPI symptoms should be carefully monitored.

Major finding: During a mean follow-up of 3 months, none of the patients developed clinically significant steatorrhoea or fat malabsorption in postoperative setting. Incidence of EPI (fecal elastase less than 200 μg/g) following gastric resectional surgery was 33.3%.

Study details: This prospective study included 60 patients who received total or subtotal gastrectomy for adenocarcinoma of the stomach. Pre- and postoperative FE testing was done in 27 patients.

Disclosures: This study was funded by the Internal Fluid research Grant, Christian Medical College, Vellore, India. The authors declared no conflicts of interest.

Source: Sridhar RP et al. Indian J Surg Oncol. 2021 Apr 5. doi: 10.1007/s13193-021-01315-7.

Key clinical point: The clinical presentation of exocrine pancreatic insufficiency (EPI) is probably mild in the early postoperative period following gastric resectional surgery. Thus, routine pancreatic supplementation may not be needed after surgery; however, worsening of EPI symptoms should be carefully monitored.

Major finding: During a mean follow-up of 3 months, none of the patients developed clinically significant steatorrhoea or fat malabsorption in postoperative setting. Incidence of EPI (fecal elastase less than 200 μg/g) following gastric resectional surgery was 33.3%.

Study details: This prospective study included 60 patients who received total or subtotal gastrectomy for adenocarcinoma of the stomach. Pre- and postoperative FE testing was done in 27 patients.

Disclosures: This study was funded by the Internal Fluid research Grant, Christian Medical College, Vellore, India. The authors declared no conflicts of interest.

Source: Sridhar RP et al. Indian J Surg Oncol. 2021 Apr 5. doi: 10.1007/s13193-021-01315-7.

Key clinical point: Exogenous digestive enzyme replacement was associated with increased weight gain and head circumference growth in very low birth weight preterm infants with growth failure and signs and symptoms of exocrine pancreatic insufficiency (EPI).

Major finding: Average daily weight gain increased from 14.4 g/kg/day to 17.4 g/kg/day (P = .001) and head circumference growth rate increased from 0.74 cm/week to 0.95 cm/week (P = .028) during 2 weeks following administration of digestive enzyme replacement.

Study details: This was a retrospective study of 132 preterm infants with gestational age below 2 weeks and birth weight below 1250 g who survived for more than 14 days. Growth restriction despite intensified nutrition and poor exocrine pancreatic function was observed in 66 and 38 infants, respectively, of which 33 infants recieved exogenous digestive enzyme replacement.

Disclosures: No specific funding source was identified. Open Access was funded by ProjektDEAL. The authors declared no conflicts of interest.

Source: Münch A et al. Eur J Pediatr. 2021 Apr 10. doi: 10.1007/s00431-021-04069-0.

Key clinical point: Exogenous digestive enzyme replacement was associated with increased weight gain and head circumference growth in very low birth weight preterm infants with growth failure and signs and symptoms of exocrine pancreatic insufficiency (EPI).

Major finding: Average daily weight gain increased from 14.4 g/kg/day to 17.4 g/kg/day (P = .001) and head circumference growth rate increased from 0.74 cm/week to 0.95 cm/week (P = .028) during 2 weeks following administration of digestive enzyme replacement.

Study details: This was a retrospective study of 132 preterm infants with gestational age below 2 weeks and birth weight below 1250 g who survived for more than 14 days. Growth restriction despite intensified nutrition and poor exocrine pancreatic function was observed in 66 and 38 infants, respectively, of which 33 infants recieved exogenous digestive enzyme replacement.

Disclosures: No specific funding source was identified. Open Access was funded by ProjektDEAL. The authors declared no conflicts of interest.

Source: Münch A et al. Eur J Pediatr. 2021 Apr 10. doi: 10.1007/s00431-021-04069-0.

Key clinical point: Exogenous digestive enzyme replacement was associated with increased weight gain and head circumference growth in very low birth weight preterm infants with growth failure and signs and symptoms of exocrine pancreatic insufficiency (EPI).

Major finding: Average daily weight gain increased from 14.4 g/kg/day to 17.4 g/kg/day (P = .001) and head circumference growth rate increased from 0.74 cm/week to 0.95 cm/week (P = .028) during 2 weeks following administration of digestive enzyme replacement.

Study details: This was a retrospective study of 132 preterm infants with gestational age below 2 weeks and birth weight below 1250 g who survived for more than 14 days. Growth restriction despite intensified nutrition and poor exocrine pancreatic function was observed in 66 and 38 infants, respectively, of which 33 infants recieved exogenous digestive enzyme replacement.

Disclosures: No specific funding source was identified. Open Access was funded by ProjektDEAL. The authors declared no conflicts of interest.

Source: Münch A et al. Eur J Pediatr. 2021 Apr 10. doi: 10.1007/s00431-021-04069-0.

The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.

Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.

The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.

Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.

He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”

The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
 

FDA breakthrough designation

SEP-363856 has a completely different mechanism of action from currently available antipsychotics.

In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.

Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.

In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.

They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.

Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.

The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.

Significant improvement

The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).

Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).

In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.

During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.

PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.

When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.

Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.

In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
 

Still in development

Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.

Courtesy Mount Sinai Health System

Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. “The proof of the pudding is phase 3, and we have to wait and see,” he added.

“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”

He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.

“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.

“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.

Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.

However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.

The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.

A version of this article first appeared on Medscape.com.

The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.

Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.

The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.

Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.

He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”

The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
 

FDA breakthrough designation

SEP-363856 has a completely different mechanism of action from currently available antipsychotics.

In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.

Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.

In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.

They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.

Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.

The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.

Significant improvement

The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).

Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).

In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.

During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.

PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.

When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.

Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.

In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
 

Still in development

Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.

Courtesy Mount Sinai Health System

Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. “The proof of the pudding is phase 3, and we have to wait and see,” he added.

“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”

He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.

“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.

“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.

Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.

However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.

The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.

A version of this article first appeared on Medscape.com.

The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.

Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.

The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.

Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.

He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”

The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
 

FDA breakthrough designation

SEP-363856 has a completely different mechanism of action from currently available antipsychotics.

In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.

Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.

In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.

They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.

Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.

The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.

Significant improvement

The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).

Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).

In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.

During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.

PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.

When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.

Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.

In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
 

Still in development

Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.

Courtesy Mount Sinai Health System

Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. “The proof of the pudding is phase 3, and we have to wait and see,” he added.

“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”

He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.

“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.

“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.

Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.

However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.

The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.

A version of this article first appeared on Medscape.com.

Key clinical point: Exocrine pancreatic function appeared normal in critically ill children during the first week of admission to the pediatric intensive care unit (PICU).

Major finding: Fecal elastase-1 concentrations were normal (1-2 μg/g; n=10). Mean amylase levels on admission and PICU discharge were 13 (interquartile range [IQR], 6.5-41.5) U/L and 15.5 (IQR, 7-44) U/L, respectively. Mean lipase levels on admission and at PICU discharge were 11 (IQR, 6.8-19.5) U/L and 16.5 (IQR, 12.3-36.8) U/L, respectively.

Study details: Findings are from a prospective observational study that included 15 critically ill children (median age, 5 months) admitted to PICU (median stay, 15 days) at a tertiary hospital in Madrid, Spain.

Disclosures: No specific funding source was identified. The authors did not report any disclosures.

Source: Solana Garcia MJ et al. Pedia Crit Care Med. 2021 Mar doi: 10.1097/01.pcc.0000738960.34833.ce.

Key clinical point: Exocrine pancreatic function appeared normal in critically ill children during the first week of admission to the pediatric intensive care unit (PICU).

Major finding: Fecal elastase-1 concentrations were normal (1-2 μg/g; n=10). Mean amylase levels on admission and PICU discharge were 13 (interquartile range [IQR], 6.5-41.5) U/L and 15.5 (IQR, 7-44) U/L, respectively. Mean lipase levels on admission and at PICU discharge were 11 (IQR, 6.8-19.5) U/L and 16.5 (IQR, 12.3-36.8) U/L, respectively.

Study details: Findings are from a prospective observational study that included 15 critically ill children (median age, 5 months) admitted to PICU (median stay, 15 days) at a tertiary hospital in Madrid, Spain.

Disclosures: No specific funding source was identified. The authors did not report any disclosures.

Source: Solana Garcia MJ et al. Pedia Crit Care Med. 2021 Mar doi: 10.1097/01.pcc.0000738960.34833.ce.

Key clinical point: Exocrine pancreatic function appeared normal in critically ill children during the first week of admission to the pediatric intensive care unit (PICU).

Major finding: Fecal elastase-1 concentrations were normal (1-2 μg/g; n=10). Mean amylase levels on admission and PICU discharge were 13 (interquartile range [IQR], 6.5-41.5) U/L and 15.5 (IQR, 7-44) U/L, respectively. Mean lipase levels on admission and at PICU discharge were 11 (IQR, 6.8-19.5) U/L and 16.5 (IQR, 12.3-36.8) U/L, respectively.

Study details: Findings are from a prospective observational study that included 15 critically ill children (median age, 5 months) admitted to PICU (median stay, 15 days) at a tertiary hospital in Madrid, Spain.

Disclosures: No specific funding source was identified. The authors did not report any disclosures.

Source: Solana Garcia MJ et al. Pedia Crit Care Med. 2021 Mar doi: 10.1097/01.pcc.0000738960.34833.ce.