Clinical Edge Journal Scan Commentary: Prostate Cancer December 2021

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Mark Klein, MD
            The introduction and subsequent application of the use of prostate specific antigen (PSA) for use in the detection and monitoring of prostate cancer demonstrates how challenging, and sometimes controversial, development of appropriate screening strategies in a cancer with highly heterogenous outcomes can be. In 2012, the United States Preventive Services Task Force (USPSTF) published a “D” recommendation (recommended against using PSA for screening) for the use of PSA for screening for prostate cancer, and PSA-based screening rates subsequently declined. However, based on new evidence, in 2017 the USPSTF upgraded the recommendation to a “C” recommendation (endorsing individual decision-making). Leapman et al examined claims from an insurance company (Blue Cross/Blue Shield) from 2016 to 2019 to determine if PSA testing rates increased after that decision. Over that time, PSA testing increased from 32.5 to 36.5 tests per 100 person-years, corresponding to a relative increase of 12.5%. While no definitive conclusions for addressing individual patients can be identified from this study, the results suggest that the USPSTF recommendations hold significant weight.

 

            Racial and ethnic disparities in prostate cancer diagnosis and treatment are well recognized. Prostate magnetic resonance imaging (MRI) as part of a diagnostic approach for people with elevated PSA may decrease unnecessary biopsies or better direct biopsies based on results, and its use is increasing significantly. Abashidze et al examined Medicare claims between 2011 and 2017 to determine if racial disparities were present with respect to the use of prostate MRI. Compared with White men, Black, Asian, and Hispanic men were less likely to have a prostate MRI within 180 days after an elevated PSA (results stratified at 2.5, 4, or 10 ng/mL). The differences were most pronounced for patients with a PSA at 4 ng/mL or higher. The results suggest that providers should be aware of potential system and individual factors that influence racial and ethnic disparities in the use of prostate MRI.

            Studies designed to evaluate germline and somatic genomic abnormalities in prostate cancer have come to the forefront in the last decade. Lynch syndrome is an inherited cancer syndrome of abnormalities in at least one of the commonly recognized mismatch repair genes: MLH1, MSH2, MSH6, or PMS2. While testing for mismatch repair deficiency is recommended in the advanced setting where systemic therapy is being considered, such testing outside of known family history is unclear in the setting of screening for prostate cancer. Bancroft et al compared PSA levels (and prostate cancer incidence) as part of baseline screening between carriers of one of mismatch repair genes (MLH1, MSH2, MSH6) and non-carrier controls. Carriers of MLH1 and MSH6 variants had a higher incidence of prostate cancer compared with controls. While not yet recommended for standard practice, further studies will be needed to verify these compelling results.

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Minneapolis VA Health Care System

University of Minnesota

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Dr. Klein scans the journals, so you don’t have to!
Dr. Klein scans the journals, so you don’t have to!

Mark Klein, MD
            The introduction and subsequent application of the use of prostate specific antigen (PSA) for use in the detection and monitoring of prostate cancer demonstrates how challenging, and sometimes controversial, development of appropriate screening strategies in a cancer with highly heterogenous outcomes can be. In 2012, the United States Preventive Services Task Force (USPSTF) published a “D” recommendation (recommended against using PSA for screening) for the use of PSA for screening for prostate cancer, and PSA-based screening rates subsequently declined. However, based on new evidence, in 2017 the USPSTF upgraded the recommendation to a “C” recommendation (endorsing individual decision-making). Leapman et al examined claims from an insurance company (Blue Cross/Blue Shield) from 2016 to 2019 to determine if PSA testing rates increased after that decision. Over that time, PSA testing increased from 32.5 to 36.5 tests per 100 person-years, corresponding to a relative increase of 12.5%. While no definitive conclusions for addressing individual patients can be identified from this study, the results suggest that the USPSTF recommendations hold significant weight.

 

            Racial and ethnic disparities in prostate cancer diagnosis and treatment are well recognized. Prostate magnetic resonance imaging (MRI) as part of a diagnostic approach for people with elevated PSA may decrease unnecessary biopsies or better direct biopsies based on results, and its use is increasing significantly. Abashidze et al examined Medicare claims between 2011 and 2017 to determine if racial disparities were present with respect to the use of prostate MRI. Compared with White men, Black, Asian, and Hispanic men were less likely to have a prostate MRI within 180 days after an elevated PSA (results stratified at 2.5, 4, or 10 ng/mL). The differences were most pronounced for patients with a PSA at 4 ng/mL or higher. The results suggest that providers should be aware of potential system and individual factors that influence racial and ethnic disparities in the use of prostate MRI.

            Studies designed to evaluate germline and somatic genomic abnormalities in prostate cancer have come to the forefront in the last decade. Lynch syndrome is an inherited cancer syndrome of abnormalities in at least one of the commonly recognized mismatch repair genes: MLH1, MSH2, MSH6, or PMS2. While testing for mismatch repair deficiency is recommended in the advanced setting where systemic therapy is being considered, such testing outside of known family history is unclear in the setting of screening for prostate cancer. Bancroft et al compared PSA levels (and prostate cancer incidence) as part of baseline screening between carriers of one of mismatch repair genes (MLH1, MSH2, MSH6) and non-carrier controls. Carriers of MLH1 and MSH6 variants had a higher incidence of prostate cancer compared with controls. While not yet recommended for standard practice, further studies will be needed to verify these compelling results.

Mark Klein, MD
            The introduction and subsequent application of the use of prostate specific antigen (PSA) for use in the detection and monitoring of prostate cancer demonstrates how challenging, and sometimes controversial, development of appropriate screening strategies in a cancer with highly heterogenous outcomes can be. In 2012, the United States Preventive Services Task Force (USPSTF) published a “D” recommendation (recommended against using PSA for screening) for the use of PSA for screening for prostate cancer, and PSA-based screening rates subsequently declined. However, based on new evidence, in 2017 the USPSTF upgraded the recommendation to a “C” recommendation (endorsing individual decision-making). Leapman et al examined claims from an insurance company (Blue Cross/Blue Shield) from 2016 to 2019 to determine if PSA testing rates increased after that decision. Over that time, PSA testing increased from 32.5 to 36.5 tests per 100 person-years, corresponding to a relative increase of 12.5%. While no definitive conclusions for addressing individual patients can be identified from this study, the results suggest that the USPSTF recommendations hold significant weight.

 

            Racial and ethnic disparities in prostate cancer diagnosis and treatment are well recognized. Prostate magnetic resonance imaging (MRI) as part of a diagnostic approach for people with elevated PSA may decrease unnecessary biopsies or better direct biopsies based on results, and its use is increasing significantly. Abashidze et al examined Medicare claims between 2011 and 2017 to determine if racial disparities were present with respect to the use of prostate MRI. Compared with White men, Black, Asian, and Hispanic men were less likely to have a prostate MRI within 180 days after an elevated PSA (results stratified at 2.5, 4, or 10 ng/mL). The differences were most pronounced for patients with a PSA at 4 ng/mL or higher. The results suggest that providers should be aware of potential system and individual factors that influence racial and ethnic disparities in the use of prostate MRI.

            Studies designed to evaluate germline and somatic genomic abnormalities in prostate cancer have come to the forefront in the last decade. Lynch syndrome is an inherited cancer syndrome of abnormalities in at least one of the commonly recognized mismatch repair genes: MLH1, MSH2, MSH6, or PMS2. While testing for mismatch repair deficiency is recommended in the advanced setting where systemic therapy is being considered, such testing outside of known family history is unclear in the setting of screening for prostate cancer. Bancroft et al compared PSA levels (and prostate cancer incidence) as part of baseline screening between carriers of one of mismatch repair genes (MLH1, MSH2, MSH6) and non-carrier controls. Carriers of MLH1 and MSH6 variants had a higher incidence of prostate cancer compared with controls. While not yet recommended for standard practice, further studies will be needed to verify these compelling results.

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Clinical Edge Journal Scan Commentary: HCC December 2021

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Dr. Damjanov scans the journals, so you don’t have to!

Nevena Damjanov, MD
Hepatocellular carcinoma (HCC) benefits from multidisciplinary care. This month we will review articles that address different approaches to the treatment for HCC, their outcomes, and potential complications.

Laparoscopic HCC resections are increasing worldwide. Ivanics et al. report on a retrospective single-institution experience in North America that involves 149 patients who were matched by propensity score. Laparoscopic liver resection was performed in 57, and open liver resection was completed in 92. The laparoscopic liver resection group experienced a lower number of serious complications (14% vs 29%; P = .01). The 1-year overall survival (OS) rate was 90.9% vs 91.3% in the laparoscopic liver resection versus open liver resection group, while 3-year OS was 79.3% vs 88.5%, and 5-year OS was 70.5% vs 83.1% (P = .26). The cumulative incidence of recurrence at 1 year was 31.1% vs 18.9% in the laparoscopic liver resection versus open liver resection group, at 3 years was 59.7% vs 40.6%, and at 5 years was 62.9% vs 49.2% (P = .06). The authors concluded that laparoscopic HCC resection had fewer short-term complications, and statistically equivalent tumor control, compared to open liver resection, and should be considered as an option for treatment of patients with resectable liver cancer.

Radioembolization is a common treatment for liver-dominant HCC. Selective internal radiation therapy (SIRT) has a high objective response rate, but has yet to demonstrate a OS benefit. This could be due to incidental damage to the healthy liver, resulting in scarring, liver decompensation and a shorter survival. Van Doom et al. retrospectively analyzed 69 patients with advanced HCC who underwent SIRT. The primary outcome was the percentage of patients who developed Child-Pugh (CP) ≥ B7 liver disease after SIRT. The secondary outcomes were OS and response. After a median follow-up of 30 months, 38/69 patients (55%) developed CP ≥ B7. A lower ALBI score at baseline was significantly associated with a better outcome. The median OS in the SIRT-treated patients was 18 months (95% CI 14–22) compared to a case-matched cohort of 300 patients treated with sorafenib between 2007 and 2016 where the median OS was 8 months (95% CI 6–12; p = 0.0027). The authors concluded that patients with intermediate- or advanced-stage HCC treated with SIRT have a substantial risk of developing liver decompensation, but improved patient selection using the ALBI score may mitigate this risk. Note is made that the sorafenib patients were treated at a time when limited systemic options were available.

Finally, Peng et al. analyzed 699 adults with newly diagnosed HCC who were initially treated with transarterial chemoembolization (TACE) between 2010 and 2013. Initial treatment with TACE resulted in a complete response (CR) in 22.3% of the patients. The patients with a CR had a better OS than those who did not achieve CR (35.8 vs 24.0 months, P < 0.001). Predictors of lower likelihood of CR included CP B cirrhosis, higher tumor load, bilobar tumor, alpha-fetoprotein (AFP) level ≥20, and platelet counts >150,000. The authors concluded that TACE is an excellent treatment for selected patients with localized HCC.

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Nevena Damjanov, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: QED; Eisai

Received research grant from: Basilea; Bristol-Myers Squibb; Merck

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Nevena Damjanov, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: QED; Eisai

Received research grant from: Basilea; Bristol-Myers Squibb; Merck

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Nevena Damjanov, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: QED; Eisai

Received research grant from: Basilea; Bristol-Myers Squibb; Merck

Dr. Damjanov scans the journals, so you don’t have to!
Dr. Damjanov scans the journals, so you don’t have to!

Nevena Damjanov, MD
Hepatocellular carcinoma (HCC) benefits from multidisciplinary care. This month we will review articles that address different approaches to the treatment for HCC, their outcomes, and potential complications.

Laparoscopic HCC resections are increasing worldwide. Ivanics et al. report on a retrospective single-institution experience in North America that involves 149 patients who were matched by propensity score. Laparoscopic liver resection was performed in 57, and open liver resection was completed in 92. The laparoscopic liver resection group experienced a lower number of serious complications (14% vs 29%; P = .01). The 1-year overall survival (OS) rate was 90.9% vs 91.3% in the laparoscopic liver resection versus open liver resection group, while 3-year OS was 79.3% vs 88.5%, and 5-year OS was 70.5% vs 83.1% (P = .26). The cumulative incidence of recurrence at 1 year was 31.1% vs 18.9% in the laparoscopic liver resection versus open liver resection group, at 3 years was 59.7% vs 40.6%, and at 5 years was 62.9% vs 49.2% (P = .06). The authors concluded that laparoscopic HCC resection had fewer short-term complications, and statistically equivalent tumor control, compared to open liver resection, and should be considered as an option for treatment of patients with resectable liver cancer.

Radioembolization is a common treatment for liver-dominant HCC. Selective internal radiation therapy (SIRT) has a high objective response rate, but has yet to demonstrate a OS benefit. This could be due to incidental damage to the healthy liver, resulting in scarring, liver decompensation and a shorter survival. Van Doom et al. retrospectively analyzed 69 patients with advanced HCC who underwent SIRT. The primary outcome was the percentage of patients who developed Child-Pugh (CP) ≥ B7 liver disease after SIRT. The secondary outcomes were OS and response. After a median follow-up of 30 months, 38/69 patients (55%) developed CP ≥ B7. A lower ALBI score at baseline was significantly associated with a better outcome. The median OS in the SIRT-treated patients was 18 months (95% CI 14–22) compared to a case-matched cohort of 300 patients treated with sorafenib between 2007 and 2016 where the median OS was 8 months (95% CI 6–12; p = 0.0027). The authors concluded that patients with intermediate- or advanced-stage HCC treated with SIRT have a substantial risk of developing liver decompensation, but improved patient selection using the ALBI score may mitigate this risk. Note is made that the sorafenib patients were treated at a time when limited systemic options were available.

Finally, Peng et al. analyzed 699 adults with newly diagnosed HCC who were initially treated with transarterial chemoembolization (TACE) between 2010 and 2013. Initial treatment with TACE resulted in a complete response (CR) in 22.3% of the patients. The patients with a CR had a better OS than those who did not achieve CR (35.8 vs 24.0 months, P < 0.001). Predictors of lower likelihood of CR included CP B cirrhosis, higher tumor load, bilobar tumor, alpha-fetoprotein (AFP) level ≥20, and platelet counts >150,000. The authors concluded that TACE is an excellent treatment for selected patients with localized HCC.

Nevena Damjanov, MD
Hepatocellular carcinoma (HCC) benefits from multidisciplinary care. This month we will review articles that address different approaches to the treatment for HCC, their outcomes, and potential complications.

Laparoscopic HCC resections are increasing worldwide. Ivanics et al. report on a retrospective single-institution experience in North America that involves 149 patients who were matched by propensity score. Laparoscopic liver resection was performed in 57, and open liver resection was completed in 92. The laparoscopic liver resection group experienced a lower number of serious complications (14% vs 29%; P = .01). The 1-year overall survival (OS) rate was 90.9% vs 91.3% in the laparoscopic liver resection versus open liver resection group, while 3-year OS was 79.3% vs 88.5%, and 5-year OS was 70.5% vs 83.1% (P = .26). The cumulative incidence of recurrence at 1 year was 31.1% vs 18.9% in the laparoscopic liver resection versus open liver resection group, at 3 years was 59.7% vs 40.6%, and at 5 years was 62.9% vs 49.2% (P = .06). The authors concluded that laparoscopic HCC resection had fewer short-term complications, and statistically equivalent tumor control, compared to open liver resection, and should be considered as an option for treatment of patients with resectable liver cancer.

Radioembolization is a common treatment for liver-dominant HCC. Selective internal radiation therapy (SIRT) has a high objective response rate, but has yet to demonstrate a OS benefit. This could be due to incidental damage to the healthy liver, resulting in scarring, liver decompensation and a shorter survival. Van Doom et al. retrospectively analyzed 69 patients with advanced HCC who underwent SIRT. The primary outcome was the percentage of patients who developed Child-Pugh (CP) ≥ B7 liver disease after SIRT. The secondary outcomes were OS and response. After a median follow-up of 30 months, 38/69 patients (55%) developed CP ≥ B7. A lower ALBI score at baseline was significantly associated with a better outcome. The median OS in the SIRT-treated patients was 18 months (95% CI 14–22) compared to a case-matched cohort of 300 patients treated with sorafenib between 2007 and 2016 where the median OS was 8 months (95% CI 6–12; p = 0.0027). The authors concluded that patients with intermediate- or advanced-stage HCC treated with SIRT have a substantial risk of developing liver decompensation, but improved patient selection using the ALBI score may mitigate this risk. Note is made that the sorafenib patients were treated at a time when limited systemic options were available.

Finally, Peng et al. analyzed 699 adults with newly diagnosed HCC who were initially treated with transarterial chemoembolization (TACE) between 2010 and 2013. Initial treatment with TACE resulted in a complete response (CR) in 22.3% of the patients. The patients with a CR had a better OS than those who did not achieve CR (35.8 vs 24.0 months, P < 0.001). Predictors of lower likelihood of CR included CP B cirrhosis, higher tumor load, bilobar tumor, alpha-fetoprotein (AFP) level ≥20, and platelet counts >150,000. The authors concluded that TACE is an excellent treatment for selected patients with localized HCC.

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Clinical Edge Journal Scan Commentary: CRC December 2021

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Dr. Weinberg scans the journals, so you don’t have to!

Benjamin A. Weinberg, MD
Over the last 25 years there has been a dramatic rise of colorectal cancer in individuals under age 50. The reasons behind this trend remain largely unknown, although the coincident epidemics of obesity and diabetes are often blamed. There is a growing body of evidence that patients with young-onset colorectal cancer have more aggressive disease than their older counterparts. The large, international IDEA collaboration was a collection of randomized trials examining 3 vs 6 months of adjuvant fluoropyrimidine and oxaliplatin chemotherapy in over 16,000 patients with stage II or III colorectal cancer. Fontana and colleagues compared the 9.6% of patients with who were diagnosed before age 50 to the over age 50 group with high risk stage III colorectal cancer, and they showed that younger patients had worse survival outcomes regardless of duration of chemotherapy, despite having a better baseline performance status and a higher likelihood of completing planned adjuvant chemotherapy. These findings confirm the suspicion that young-onset colorectal cancer is biologically distinct from older-onset colorectal cancer and galvanizes the larger oncology research community to better understand why young-onset colorectal cancer occurs and how best to treat it.

Throughout the oncology landscape we are trying to incorporate immunotherapy into the treatment paradigm, and while this has been very successful in certain types of cancer (e.g. melanoma, lung cancer, and kidney cancer), colorectal cancer has been mostly left behind by the immunotherapy revolution to date. In a phase II single-arm study out of China, Lin and coworkers added camrelizumab, an anti-PD-1 monoclonal antibody, to neoadjuvant CAPOX chemotherapy following short-course radiation for patients with locally advanced rectal cancer. Of 27 evaluable patients, 13 had a pathological complete response (pCR, 48.1%), all but one of whom were mismatch repair proficient and unlikely to respond to immunotherapy. This small study laid the groundwork for an ongoing, randomized phase III study which is designed to demonstrate a significant increase in the pCR rate compared to standard neoadjuvant long-course chemoradiation and chemotherapy.

Finally, there has been excitement in the advanced setting of adding regorafenib, an oral poly-tyrosine kinase inhibitor, to immune checkpoint inhibitors for patients with mismatch repair proficient disease. Japanese data suggested a benefit from this combination which has not been fully borne out in the American experience. Yang and coauthors retrospectively analyzed the experience of regorafenib plus immune checkpoint inhibitors in mismatch repair proficient metastatic colorectal cancer patients at 14 Chinese medical centers and determined that the objective response rate in 82 patients was only 5% with a 45% stable disease rate. However, the median duration of disease control (stable disease or better) was 6.3 months which is clinically meaningful in this population. Moreover, 65% of patients have liver metastases which have proven to be more refractory to this combination in the American data. While we await more prospective studies of this combination, we continue to hold out hope that it may be a novel therapeutic option which is so desperately needed for patients with metastatic colorectal cancer.

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Benjamin A. Weinberg, MD

Disclosures: speaker/advisor for Bayer, Taiho, Sirtex, HalioDx, Lilly, AstraZeneca/Daiichi Sankyo, Blueprint Medicines, research support from Ipsen, G1 Therapeutics.

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Benjamin A. Weinberg, MD

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Benjamin A. Weinberg, MD

Disclosures: speaker/advisor for Bayer, Taiho, Sirtex, HalioDx, Lilly, AstraZeneca/Daiichi Sankyo, Blueprint Medicines, research support from Ipsen, G1 Therapeutics.

Dr. Weinberg scans the journals, so you don’t have to!
Dr. Weinberg scans the journals, so you don’t have to!

Benjamin A. Weinberg, MD
Over the last 25 years there has been a dramatic rise of colorectal cancer in individuals under age 50. The reasons behind this trend remain largely unknown, although the coincident epidemics of obesity and diabetes are often blamed. There is a growing body of evidence that patients with young-onset colorectal cancer have more aggressive disease than their older counterparts. The large, international IDEA collaboration was a collection of randomized trials examining 3 vs 6 months of adjuvant fluoropyrimidine and oxaliplatin chemotherapy in over 16,000 patients with stage II or III colorectal cancer. Fontana and colleagues compared the 9.6% of patients with who were diagnosed before age 50 to the over age 50 group with high risk stage III colorectal cancer, and they showed that younger patients had worse survival outcomes regardless of duration of chemotherapy, despite having a better baseline performance status and a higher likelihood of completing planned adjuvant chemotherapy. These findings confirm the suspicion that young-onset colorectal cancer is biologically distinct from older-onset colorectal cancer and galvanizes the larger oncology research community to better understand why young-onset colorectal cancer occurs and how best to treat it.

Throughout the oncology landscape we are trying to incorporate immunotherapy into the treatment paradigm, and while this has been very successful in certain types of cancer (e.g. melanoma, lung cancer, and kidney cancer), colorectal cancer has been mostly left behind by the immunotherapy revolution to date. In a phase II single-arm study out of China, Lin and coworkers added camrelizumab, an anti-PD-1 monoclonal antibody, to neoadjuvant CAPOX chemotherapy following short-course radiation for patients with locally advanced rectal cancer. Of 27 evaluable patients, 13 had a pathological complete response (pCR, 48.1%), all but one of whom were mismatch repair proficient and unlikely to respond to immunotherapy. This small study laid the groundwork for an ongoing, randomized phase III study which is designed to demonstrate a significant increase in the pCR rate compared to standard neoadjuvant long-course chemoradiation and chemotherapy.

Finally, there has been excitement in the advanced setting of adding regorafenib, an oral poly-tyrosine kinase inhibitor, to immune checkpoint inhibitors for patients with mismatch repair proficient disease. Japanese data suggested a benefit from this combination which has not been fully borne out in the American experience. Yang and coauthors retrospectively analyzed the experience of regorafenib plus immune checkpoint inhibitors in mismatch repair proficient metastatic colorectal cancer patients at 14 Chinese medical centers and determined that the objective response rate in 82 patients was only 5% with a 45% stable disease rate. However, the median duration of disease control (stable disease or better) was 6.3 months which is clinically meaningful in this population. Moreover, 65% of patients have liver metastases which have proven to be more refractory to this combination in the American data. While we await more prospective studies of this combination, we continue to hold out hope that it may be a novel therapeutic option which is so desperately needed for patients with metastatic colorectal cancer.

Benjamin A. Weinberg, MD
Over the last 25 years there has been a dramatic rise of colorectal cancer in individuals under age 50. The reasons behind this trend remain largely unknown, although the coincident epidemics of obesity and diabetes are often blamed. There is a growing body of evidence that patients with young-onset colorectal cancer have more aggressive disease than their older counterparts. The large, international IDEA collaboration was a collection of randomized trials examining 3 vs 6 months of adjuvant fluoropyrimidine and oxaliplatin chemotherapy in over 16,000 patients with stage II or III colorectal cancer. Fontana and colleagues compared the 9.6% of patients with who were diagnosed before age 50 to the over age 50 group with high risk stage III colorectal cancer, and they showed that younger patients had worse survival outcomes regardless of duration of chemotherapy, despite having a better baseline performance status and a higher likelihood of completing planned adjuvant chemotherapy. These findings confirm the suspicion that young-onset colorectal cancer is biologically distinct from older-onset colorectal cancer and galvanizes the larger oncology research community to better understand why young-onset colorectal cancer occurs and how best to treat it.

Throughout the oncology landscape we are trying to incorporate immunotherapy into the treatment paradigm, and while this has been very successful in certain types of cancer (e.g. melanoma, lung cancer, and kidney cancer), colorectal cancer has been mostly left behind by the immunotherapy revolution to date. In a phase II single-arm study out of China, Lin and coworkers added camrelizumab, an anti-PD-1 monoclonal antibody, to neoadjuvant CAPOX chemotherapy following short-course radiation for patients with locally advanced rectal cancer. Of 27 evaluable patients, 13 had a pathological complete response (pCR, 48.1%), all but one of whom were mismatch repair proficient and unlikely to respond to immunotherapy. This small study laid the groundwork for an ongoing, randomized phase III study which is designed to demonstrate a significant increase in the pCR rate compared to standard neoadjuvant long-course chemoradiation and chemotherapy.

Finally, there has been excitement in the advanced setting of adding regorafenib, an oral poly-tyrosine kinase inhibitor, to immune checkpoint inhibitors for patients with mismatch repair proficient disease. Japanese data suggested a benefit from this combination which has not been fully borne out in the American experience. Yang and coauthors retrospectively analyzed the experience of regorafenib plus immune checkpoint inhibitors in mismatch repair proficient metastatic colorectal cancer patients at 14 Chinese medical centers and determined that the objective response rate in 82 patients was only 5% with a 45% stable disease rate. However, the median duration of disease control (stable disease or better) was 6.3 months which is clinically meaningful in this population. Moreover, 65% of patients have liver metastases which have proven to be more refractory to this combination in the American data. While we await more prospective studies of this combination, we continue to hold out hope that it may be a novel therapeutic option which is so desperately needed for patients with metastatic colorectal cancer.

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Bipolar loop resectoscopic slicing aids in safer and faster enucleation of submucous uterine fibroids

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Key clinical point: Enucleation of submucous uterine fibroids (UF) under hysteroscopy can be achieved by a modified resectoscopic slicing using a bipolar loop, which appeared safe and faster compared with classical resectoscopic myomectomy.

Major finding: Mean operation time (22.9 minutes vs 38.9 minutes; P < .001) and volume of mean distending media (1,495.6 mL vs 2,393.1 mL; P < .001) were significantly shorter in the modified vs classical resectoscopic slicing group. The classical group witnessed 3 cases of fluid overload and 1 case of uterine perforation, whereas none of these postoperative complications occurred in the modified technique group.

Study details: Findings are from a retrospective study including 55 women with submucous UFs, of which 19 women underwent modified resectoscopic slicing and 36 women underwent the classical resectoscopic myomectomy.

Disclosures: This study was funded by Shanghai Municipal Health Commission, China. The authors declared no conflict of interests.

Source: Zhang W et al. Front Surg. 2021 Nov 10. doi: 10.3389/fsurg.2021.746936.

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Key clinical point: Enucleation of submucous uterine fibroids (UF) under hysteroscopy can be achieved by a modified resectoscopic slicing using a bipolar loop, which appeared safe and faster compared with classical resectoscopic myomectomy.

Major finding: Mean operation time (22.9 minutes vs 38.9 minutes; P < .001) and volume of mean distending media (1,495.6 mL vs 2,393.1 mL; P < .001) were significantly shorter in the modified vs classical resectoscopic slicing group. The classical group witnessed 3 cases of fluid overload and 1 case of uterine perforation, whereas none of these postoperative complications occurred in the modified technique group.

Study details: Findings are from a retrospective study including 55 women with submucous UFs, of which 19 women underwent modified resectoscopic slicing and 36 women underwent the classical resectoscopic myomectomy.

Disclosures: This study was funded by Shanghai Municipal Health Commission, China. The authors declared no conflict of interests.

Source: Zhang W et al. Front Surg. 2021 Nov 10. doi: 10.3389/fsurg.2021.746936.

Key clinical point: Enucleation of submucous uterine fibroids (UF) under hysteroscopy can be achieved by a modified resectoscopic slicing using a bipolar loop, which appeared safe and faster compared with classical resectoscopic myomectomy.

Major finding: Mean operation time (22.9 minutes vs 38.9 minutes; P < .001) and volume of mean distending media (1,495.6 mL vs 2,393.1 mL; P < .001) were significantly shorter in the modified vs classical resectoscopic slicing group. The classical group witnessed 3 cases of fluid overload and 1 case of uterine perforation, whereas none of these postoperative complications occurred in the modified technique group.

Study details: Findings are from a retrospective study including 55 women with submucous UFs, of which 19 women underwent modified resectoscopic slicing and 36 women underwent the classical resectoscopic myomectomy.

Disclosures: This study was funded by Shanghai Municipal Health Commission, China. The authors declared no conflict of interests.

Source: Zhang W et al. Front Surg. 2021 Nov 10. doi: 10.3389/fsurg.2021.746936.

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Comparative analysis of thermal ablative methods vs myomectomy for uterine fibroids

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Key clinical point: Rates of reintervention were similar, and the risk for major adverse events was lower with thermal ablative methods vs myomectomy for treating uterine fibroids (UF), suggesting that thermal ablative methods were not inferior to myomectomy for treating UFs.

Major finding: The reintervention rate was not significantly different between thermal ablative treatment and myomectomy in randomized controlled trials (RCTs; P = .094) and observational studies (P = .16). The risk for major adverse events was significantly lower with thermal ablative methods (risk ratio, 0.111; 95% CI, 0.070-0.175). The pregnancy rate was not significantly different between the groups (P = .796).

Study details: Findings are from a meta-analysis of 10 observational studies and 3 RCTs including 4,205 patients who underwent thermal ablative methods or myomectomy for the treatment of UFs.

Disclosures: This study did not report any source of funding. The authors declared no conflict of interests.

Source: Liang D et al. Int J Hyperthermia. 2021 Nov 1. doi: 10.1080/02656736.2021.1996644.

 

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Key clinical point: Rates of reintervention were similar, and the risk for major adverse events was lower with thermal ablative methods vs myomectomy for treating uterine fibroids (UF), suggesting that thermal ablative methods were not inferior to myomectomy for treating UFs.

Major finding: The reintervention rate was not significantly different between thermal ablative treatment and myomectomy in randomized controlled trials (RCTs; P = .094) and observational studies (P = .16). The risk for major adverse events was significantly lower with thermal ablative methods (risk ratio, 0.111; 95% CI, 0.070-0.175). The pregnancy rate was not significantly different between the groups (P = .796).

Study details: Findings are from a meta-analysis of 10 observational studies and 3 RCTs including 4,205 patients who underwent thermal ablative methods or myomectomy for the treatment of UFs.

Disclosures: This study did not report any source of funding. The authors declared no conflict of interests.

Source: Liang D et al. Int J Hyperthermia. 2021 Nov 1. doi: 10.1080/02656736.2021.1996644.

 

Key clinical point: Rates of reintervention were similar, and the risk for major adverse events was lower with thermal ablative methods vs myomectomy for treating uterine fibroids (UF), suggesting that thermal ablative methods were not inferior to myomectomy for treating UFs.

Major finding: The reintervention rate was not significantly different between thermal ablative treatment and myomectomy in randomized controlled trials (RCTs; P = .094) and observational studies (P = .16). The risk for major adverse events was significantly lower with thermal ablative methods (risk ratio, 0.111; 95% CI, 0.070-0.175). The pregnancy rate was not significantly different between the groups (P = .796).

Study details: Findings are from a meta-analysis of 10 observational studies and 3 RCTs including 4,205 patients who underwent thermal ablative methods or myomectomy for the treatment of UFs.

Disclosures: This study did not report any source of funding. The authors declared no conflict of interests.

Source: Liang D et al. Int J Hyperthermia. 2021 Nov 1. doi: 10.1080/02656736.2021.1996644.

 

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Simultaneous hysteromyoma enucleation and C-section safely remove anterior UFs without additional incision

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Key clinical point: Hysteromyoma enucleation performed simultaneously during the cesarean section (C-section) is safe without any surgical complications in pregnant women with anterior uterine fibroids (UF).

Major finding: The operation time (median, 83.3 minutes vs 72.5 minutes; P = .04) and postoperative hospital stays (median, 3.6 days vs 3.2 days; P = .01) were slightly longer in the group of patients whose UFs were removed by C-section incision vs those who were operated traditionally by an incision through the serous layer. Pre- and postoperative hemoglobin level, intraoperative bleeding, frequency of blood transfusion, postpartum hemorrhage, and fever were similar between both groups, with no postoperative complications observed in either group.

Study details: Findings are from a retrospective analysis of 90 pregnant women with anterior UFs who underwent hysteromyoma enucleation simultaneously during C-section.

Disclosures: This study was funded by the Fujian Provincial Maternity and Children’s Hospital Science Foundation. The authors declared no conflict of interests.

Source: Dai Y et al. BMC Pregnancy Childbirth. 2021 Nov 3. doi: 10.1186/s12884-021-04226-1.

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Key clinical point: Hysteromyoma enucleation performed simultaneously during the cesarean section (C-section) is safe without any surgical complications in pregnant women with anterior uterine fibroids (UF).

Major finding: The operation time (median, 83.3 minutes vs 72.5 minutes; P = .04) and postoperative hospital stays (median, 3.6 days vs 3.2 days; P = .01) were slightly longer in the group of patients whose UFs were removed by C-section incision vs those who were operated traditionally by an incision through the serous layer. Pre- and postoperative hemoglobin level, intraoperative bleeding, frequency of blood transfusion, postpartum hemorrhage, and fever were similar between both groups, with no postoperative complications observed in either group.

Study details: Findings are from a retrospective analysis of 90 pregnant women with anterior UFs who underwent hysteromyoma enucleation simultaneously during C-section.

Disclosures: This study was funded by the Fujian Provincial Maternity and Children’s Hospital Science Foundation. The authors declared no conflict of interests.

Source: Dai Y et al. BMC Pregnancy Childbirth. 2021 Nov 3. doi: 10.1186/s12884-021-04226-1.

Key clinical point: Hysteromyoma enucleation performed simultaneously during the cesarean section (C-section) is safe without any surgical complications in pregnant women with anterior uterine fibroids (UF).

Major finding: The operation time (median, 83.3 minutes vs 72.5 minutes; P = .04) and postoperative hospital stays (median, 3.6 days vs 3.2 days; P = .01) were slightly longer in the group of patients whose UFs were removed by C-section incision vs those who were operated traditionally by an incision through the serous layer. Pre- and postoperative hemoglobin level, intraoperative bleeding, frequency of blood transfusion, postpartum hemorrhage, and fever were similar between both groups, with no postoperative complications observed in either group.

Study details: Findings are from a retrospective analysis of 90 pregnant women with anterior UFs who underwent hysteromyoma enucleation simultaneously during C-section.

Disclosures: This study was funded by the Fujian Provincial Maternity and Children’s Hospital Science Foundation. The authors declared no conflict of interests.

Source: Dai Y et al. BMC Pregnancy Childbirth. 2021 Nov 3. doi: 10.1186/s12884-021-04226-1.

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Robotic single-port myomectomy using da Vinci SP surgical system feasible for treating symptomatic fibroids

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Key clinical point: Robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system for treating symptomatic fibroids was a feasible surgical procedure and could solve many of the ergonomic problems associated with single-port laparoscopic myomectomy (SPLM).

Major finding: Conversion to SPLM, multiport laparoscopic myomectomy, or laparotomy was not required in women with less than 7 resected fibroids (maximal diameter <10 cm) and those with at least 7 resected fibroids (maximal diameter of resected fibroids ≥10 cm). Minor postoperative complications like fever, transient ileus, and transfusion were observed in 15 women, which could be resolved by conservative treatment.

Study details: Findings are from a prospective observational study including 69 women with symptomatic fibroids who underwent myomectomy, of which 61 women underwent RSPM.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Lee JH et al. J Obstet Gynaecol Res. 2021 Oct 23. doi: 10.1111/jog.15076.

 

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Key clinical point: Robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system for treating symptomatic fibroids was a feasible surgical procedure and could solve many of the ergonomic problems associated with single-port laparoscopic myomectomy (SPLM).

Major finding: Conversion to SPLM, multiport laparoscopic myomectomy, or laparotomy was not required in women with less than 7 resected fibroids (maximal diameter <10 cm) and those with at least 7 resected fibroids (maximal diameter of resected fibroids ≥10 cm). Minor postoperative complications like fever, transient ileus, and transfusion were observed in 15 women, which could be resolved by conservative treatment.

Study details: Findings are from a prospective observational study including 69 women with symptomatic fibroids who underwent myomectomy, of which 61 women underwent RSPM.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Lee JH et al. J Obstet Gynaecol Res. 2021 Oct 23. doi: 10.1111/jog.15076.

 

Key clinical point: Robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system for treating symptomatic fibroids was a feasible surgical procedure and could solve many of the ergonomic problems associated with single-port laparoscopic myomectomy (SPLM).

Major finding: Conversion to SPLM, multiport laparoscopic myomectomy, or laparotomy was not required in women with less than 7 resected fibroids (maximal diameter <10 cm) and those with at least 7 resected fibroids (maximal diameter of resected fibroids ≥10 cm). Minor postoperative complications like fever, transient ileus, and transfusion were observed in 15 women, which could be resolved by conservative treatment.

Study details: Findings are from a prospective observational study including 69 women with symptomatic fibroids who underwent myomectomy, of which 61 women underwent RSPM.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Lee JH et al. J Obstet Gynaecol Res. 2021 Oct 23. doi: 10.1111/jog.15076.

 

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Transendometrial myomectomy bests conventional surgery for fibroids in C-section

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Key clinical point: Transendometrial myomectomy (TEM) could be more advantageous than conventional myomectomy (CM) for uterine fibroids (UF) in cesarean section (C-section) for its shorter operation time and lesser adhesion scores.

Major finding: The mean duration of surgery (50.5 minutes vs 63.6 minutes; P = .001) and adhesion scores were significantly lower (0.58 vs 1.76; P = .001) in the TEM than CM group; however, length of hospital stay, procedure-related hemoglobin difference, blood transfusion requirement, and postoperative fever were similar in both groups.

Study details: Findings are from a retrospective study including 93 patients with intramural UFs and underwent myomectomy during C-section. CM and TEM were performed in 52 and 41 patients, respectively.

Disclosures: This study did not report any source of funding. The authors declared no conflict of interests.

Source: Karaca SY et al. Eur J Obstet Gynecol. 2021 Oct 21. doi: 10.1016/j.ejogrb.2021.10.019.

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Key clinical point: Transendometrial myomectomy (TEM) could be more advantageous than conventional myomectomy (CM) for uterine fibroids (UF) in cesarean section (C-section) for its shorter operation time and lesser adhesion scores.

Major finding: The mean duration of surgery (50.5 minutes vs 63.6 minutes; P = .001) and adhesion scores were significantly lower (0.58 vs 1.76; P = .001) in the TEM than CM group; however, length of hospital stay, procedure-related hemoglobin difference, blood transfusion requirement, and postoperative fever were similar in both groups.

Study details: Findings are from a retrospective study including 93 patients with intramural UFs and underwent myomectomy during C-section. CM and TEM were performed in 52 and 41 patients, respectively.

Disclosures: This study did not report any source of funding. The authors declared no conflict of interests.

Source: Karaca SY et al. Eur J Obstet Gynecol. 2021 Oct 21. doi: 10.1016/j.ejogrb.2021.10.019.

Key clinical point: Transendometrial myomectomy (TEM) could be more advantageous than conventional myomectomy (CM) for uterine fibroids (UF) in cesarean section (C-section) for its shorter operation time and lesser adhesion scores.

Major finding: The mean duration of surgery (50.5 minutes vs 63.6 minutes; P = .001) and adhesion scores were significantly lower (0.58 vs 1.76; P = .001) in the TEM than CM group; however, length of hospital stay, procedure-related hemoglobin difference, blood transfusion requirement, and postoperative fever were similar in both groups.

Study details: Findings are from a retrospective study including 93 patients with intramural UFs and underwent myomectomy during C-section. CM and TEM were performed in 52 and 41 patients, respectively.

Disclosures: This study did not report any source of funding. The authors declared no conflict of interests.

Source: Karaca SY et al. Eur J Obstet Gynecol. 2021 Oct 21. doi: 10.1016/j.ejogrb.2021.10.019.

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Relugolix, a promising therapeutic option for uterine leiomyomas-associated menstrual blood loss

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Key clinical point: Relugolix monotherapy effectively reduced menstrual blood loss associated with uterine leiomyomas (UL) along with an acceptable tolerability profile.

Major finding: Between weeks 6 to 12, the proportion of patients with pictorial blood loss assessment chart score of less than 10 was higher in relugolix 40 mg (difference vs placebo [D], 83.3%), 20 mg (D, 42.6%), and 10 mg (D, 20.8%) treatment arms (all P < .001). Treatment-emergent adverse events were mostly mild/moderate but were more frequent in relugolix arm (85.4%-96.4%%) vs placebo (70.2%).

Study details: Findings are from a phase 2 trial, including 216 premenopausal women with UL who were randomly assigned 1:1:1:1 to receive relugolix 10 mg, 20 mg, 30 mg, 40 mg, or placebo.

Disclosures: This study was funded by Takeda Pharmaceutical Company. The lead author reported receiving consultancy fees from Takeda Pharmaceutical Company, and other authors reported being current/former employees of the company.

Source: Hoshiai H et al. BMC Womens Health. 2021 Oct 28. doi: 10.1186/s12905-021-01475-2.

 

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Key clinical point: Relugolix monotherapy effectively reduced menstrual blood loss associated with uterine leiomyomas (UL) along with an acceptable tolerability profile.

Major finding: Between weeks 6 to 12, the proportion of patients with pictorial blood loss assessment chart score of less than 10 was higher in relugolix 40 mg (difference vs placebo [D], 83.3%), 20 mg (D, 42.6%), and 10 mg (D, 20.8%) treatment arms (all P < .001). Treatment-emergent adverse events were mostly mild/moderate but were more frequent in relugolix arm (85.4%-96.4%%) vs placebo (70.2%).

Study details: Findings are from a phase 2 trial, including 216 premenopausal women with UL who were randomly assigned 1:1:1:1 to receive relugolix 10 mg, 20 mg, 30 mg, 40 mg, or placebo.

Disclosures: This study was funded by Takeda Pharmaceutical Company. The lead author reported receiving consultancy fees from Takeda Pharmaceutical Company, and other authors reported being current/former employees of the company.

Source: Hoshiai H et al. BMC Womens Health. 2021 Oct 28. doi: 10.1186/s12905-021-01475-2.

 

Key clinical point: Relugolix monotherapy effectively reduced menstrual blood loss associated with uterine leiomyomas (UL) along with an acceptable tolerability profile.

Major finding: Between weeks 6 to 12, the proportion of patients with pictorial blood loss assessment chart score of less than 10 was higher in relugolix 40 mg (difference vs placebo [D], 83.3%), 20 mg (D, 42.6%), and 10 mg (D, 20.8%) treatment arms (all P < .001). Treatment-emergent adverse events were mostly mild/moderate but were more frequent in relugolix arm (85.4%-96.4%%) vs placebo (70.2%).

Study details: Findings are from a phase 2 trial, including 216 premenopausal women with UL who were randomly assigned 1:1:1:1 to receive relugolix 10 mg, 20 mg, 30 mg, 40 mg, or placebo.

Disclosures: This study was funded by Takeda Pharmaceutical Company. The lead author reported receiving consultancy fees from Takeda Pharmaceutical Company, and other authors reported being current/former employees of the company.

Source: Hoshiai H et al. BMC Womens Health. 2021 Oct 28. doi: 10.1186/s12905-021-01475-2.

 

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Brodalumab or guselkumab: What to switch to in plaque psoriasis responding inadequately to ustekinumab?

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Key clinical point: Patients with moderate-to-severe plaque psoriasis who respond inadequately to ustekinumab should preferably be switched to brodalumab rather than guselkumab.

Major finding: Patients with an inadequate response to ustekinumab who switched to brodalumab vs guselkumab had higher Psoriasis Area Severity Index (PASI) 100 response rate at week 36 (40.3% vs 20.0%; P < .001) and PASI 90 response rate at weeks 12 (62.7% vs 48.1%; P = .002) and 36 (63.7% vs 51.1%; P = .004).

Study details: This matching-adjusted indirect comparison study employed data for patients with moderate-to-severe plaque psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) in AMAGINE-2 and -3 and or to receive guselkumab (n=135) in NAVIGATE, phase 3, trials.

Disclosures: The study was supported by LEO Pharma A/S. P Hampton and M Augustin declared receiving research/educational grants, consultation/speaker honoraria, and/or travel expenses and serving as an advisory board member or clinical trial participant for various companies, including LEO Pharma. E Borg is a current employee and JB Hansen is a former employee of LEO Pharma.

Source: Hampton P et al. Psoriasis (Auckl). 2021 Nov 3. doi: 10.2147/PTT.S326121.

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Key clinical point: Patients with moderate-to-severe plaque psoriasis who respond inadequately to ustekinumab should preferably be switched to brodalumab rather than guselkumab.

Major finding: Patients with an inadequate response to ustekinumab who switched to brodalumab vs guselkumab had higher Psoriasis Area Severity Index (PASI) 100 response rate at week 36 (40.3% vs 20.0%; P < .001) and PASI 90 response rate at weeks 12 (62.7% vs 48.1%; P = .002) and 36 (63.7% vs 51.1%; P = .004).

Study details: This matching-adjusted indirect comparison study employed data for patients with moderate-to-severe plaque psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) in AMAGINE-2 and -3 and or to receive guselkumab (n=135) in NAVIGATE, phase 3, trials.

Disclosures: The study was supported by LEO Pharma A/S. P Hampton and M Augustin declared receiving research/educational grants, consultation/speaker honoraria, and/or travel expenses and serving as an advisory board member or clinical trial participant for various companies, including LEO Pharma. E Borg is a current employee and JB Hansen is a former employee of LEO Pharma.

Source: Hampton P et al. Psoriasis (Auckl). 2021 Nov 3. doi: 10.2147/PTT.S326121.

Key clinical point: Patients with moderate-to-severe plaque psoriasis who respond inadequately to ustekinumab should preferably be switched to brodalumab rather than guselkumab.

Major finding: Patients with an inadequate response to ustekinumab who switched to brodalumab vs guselkumab had higher Psoriasis Area Severity Index (PASI) 100 response rate at week 36 (40.3% vs 20.0%; P < .001) and PASI 90 response rate at weeks 12 (62.7% vs 48.1%; P = .002) and 36 (63.7% vs 51.1%; P = .004).

Study details: This matching-adjusted indirect comparison study employed data for patients with moderate-to-severe plaque psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) in AMAGINE-2 and -3 and or to receive guselkumab (n=135) in NAVIGATE, phase 3, trials.

Disclosures: The study was supported by LEO Pharma A/S. P Hampton and M Augustin declared receiving research/educational grants, consultation/speaker honoraria, and/or travel expenses and serving as an advisory board member or clinical trial participant for various companies, including LEO Pharma. E Borg is a current employee and JB Hansen is a former employee of LEO Pharma.

Source: Hampton P et al. Psoriasis (Auckl). 2021 Nov 3. doi: 10.2147/PTT.S326121.

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