Key clinical point: Hepatectomy offers greater survival benefits than sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC) and macroscopic portal vein tumor thrombus (PVTT).

Major finding: Patients who underwent hepatectomy vs received sorafenib had a significantly longer median survival time (15.1 vs 4.5 months; hazard ratio 1.704; P  =  .0446).

Study details: This study propensity score-matched patients with advanced HCC and macroscopic PVTT invaded into an ipsilateral first-order portal branch or main trunk/contralateral portal vein who underwent hepatectomy (n = 36) with those who received sorafenib (n = 36).

Disclosures: No source of funding was reported. Some authors reported receiving grants or personal fees from various sources.

Source: Komatsu S et al. Hepatectomy versus sorafenib for advanced hepatocellular carcinoma with macroscopic portal vein tumor thrombus: A bi-institutional propensity-matched cohort study. J Hepatobiliary Pancreat Sci. 2022 (Sep 1). Doi: 10.1002/jhbp.1236

Key clinical point: Hepatectomy offers greater survival benefits than sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC) and macroscopic portal vein tumor thrombus (PVTT).

Major finding: Patients who underwent hepatectomy vs received sorafenib had a significantly longer median survival time (15.1 vs 4.5 months; hazard ratio 1.704; P  =  .0446).

Study details: This study propensity score-matched patients with advanced HCC and macroscopic PVTT invaded into an ipsilateral first-order portal branch or main trunk/contralateral portal vein who underwent hepatectomy (n = 36) with those who received sorafenib (n = 36).

Disclosures: No source of funding was reported. Some authors reported receiving grants or personal fees from various sources.

Source: Komatsu S et al. Hepatectomy versus sorafenib for advanced hepatocellular carcinoma with macroscopic portal vein tumor thrombus: A bi-institutional propensity-matched cohort study. J Hepatobiliary Pancreat Sci. 2022 (Sep 1). Doi: 10.1002/jhbp.1236

Key clinical point: Hepatectomy offers greater survival benefits than sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC) and macroscopic portal vein tumor thrombus (PVTT).

Major finding: Patients who underwent hepatectomy vs received sorafenib had a significantly longer median survival time (15.1 vs 4.5 months; hazard ratio 1.704; P  =  .0446).

Study details: This study propensity score-matched patients with advanced HCC and macroscopic PVTT invaded into an ipsilateral first-order portal branch or main trunk/contralateral portal vein who underwent hepatectomy (n = 36) with those who received sorafenib (n = 36).

Disclosures: No source of funding was reported. Some authors reported receiving grants or personal fees from various sources.

Source: Komatsu S et al. Hepatectomy versus sorafenib for advanced hepatocellular carcinoma with macroscopic portal vein tumor thrombus: A bi-institutional propensity-matched cohort study. J Hepatobiliary Pancreat Sci. 2022 (Sep 1). Doi: 10.1002/jhbp.1236

Key clinical point: Transarterial chemoembolization (TACE) via transradial access (TRA) leads to improved patient satisfaction along with similar procedural variables and safety compared with TACE via transfemoral access (TFA) in patients with hepatocellular carcinoma (HCC).

Major finding: In the TACE-TRA vs TACE-TFA group a significantly higher proportion of patients preferred the current access for their next procedure (90.8% vs 24.6%; P < .001), although between-group procedural variables (such as procedure time and length of hospital stay; all P > .05) and the incidence and severity of adverse events (all P > .05) were similar.

Study details: This single-center prospective randomized controlled trial included 130 patients with HCC who underwent TACE for the first time either via TRA (n = 65) or TFA (n = 65).

Disclosures: This study was sponsored by the Beijing Hope Run Special Fund of the Cancer Foundation of China. The authors declared no conflicts of interest.

Source: Zhang X et al. Transradial versus transfemoral access without closure device for transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized trial. Eur Radiol. 2022 (Aug 26). Doi: 10.1007/s00330-022-09038-1

Key clinical point: Transarterial chemoembolization (TACE) via transradial access (TRA) leads to improved patient satisfaction along with similar procedural variables and safety compared with TACE via transfemoral access (TFA) in patients with hepatocellular carcinoma (HCC).

Major finding: In the TACE-TRA vs TACE-TFA group a significantly higher proportion of patients preferred the current access for their next procedure (90.8% vs 24.6%; P < .001), although between-group procedural variables (such as procedure time and length of hospital stay; all P > .05) and the incidence and severity of adverse events (all P > .05) were similar.

Study details: This single-center prospective randomized controlled trial included 130 patients with HCC who underwent TACE for the first time either via TRA (n = 65) or TFA (n = 65).

Disclosures: This study was sponsored by the Beijing Hope Run Special Fund of the Cancer Foundation of China. The authors declared no conflicts of interest.

Source: Zhang X et al. Transradial versus transfemoral access without closure device for transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized trial. Eur Radiol. 2022 (Aug 26). Doi: 10.1007/s00330-022-09038-1

Key clinical point: Transarterial chemoembolization (TACE) via transradial access (TRA) leads to improved patient satisfaction along with similar procedural variables and safety compared with TACE via transfemoral access (TFA) in patients with hepatocellular carcinoma (HCC).

Major finding: In the TACE-TRA vs TACE-TFA group a significantly higher proportion of patients preferred the current access for their next procedure (90.8% vs 24.6%; P < .001), although between-group procedural variables (such as procedure time and length of hospital stay; all P > .05) and the incidence and severity of adverse events (all P > .05) were similar.

Study details: This single-center prospective randomized controlled trial included 130 patients with HCC who underwent TACE for the first time either via TRA (n = 65) or TFA (n = 65).

Disclosures: This study was sponsored by the Beijing Hope Run Special Fund of the Cancer Foundation of China. The authors declared no conflicts of interest.

Source: Zhang X et al. Transradial versus transfemoral access without closure device for transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized trial. Eur Radiol. 2022 (Aug 26). Doi: 10.1007/s00330-022-09038-1

Key clinical point: Lenvatinib may continue to benefit patients with unresectable hepatocellular carcinoma (uHCC) despite liver function deterioration to Child-Pugh class B (CP-B) after therapy initiation.

Major finding: CP-B vs CP-A patients receiving lenvatinib had a median progression-free survival (PFS) and overall survival (OS) of 3.7 months (95% CI 1.8-7.4) vs 6.5 months (95% CI 5.6-7.4) and 6.8 months (95% CI 2.6-10.3) vs 13.3 months (95% CI 11.6-16.1), respectively. CP-B patients receiving sorafenib had a median PFS and OS of only 0.5 months (95% CI 0.1-3.6) and 4.5 months (95% CI 2.9-6.1, respectively. Lenvatinib showed no new safety signals in CP-B patients.

Study details: This post hoc analysis included patients with uHCC from the REFLECT trial whose liver function deteriorated to CP-B or remained CP-A within 8 weeks of randomization to lenvatinib (CP-B: n = 60; CP-A: n = 413) or sorafenib (CP-B: n = 47; CP-A: n = 427).

Disclosures: This study was funded by Eisai Inc. and Merck Sharp & Dohme (MSD) LLC. Some authors declared serving as speakers, consultants, or advisors for various organizations, including Eisai and MSD.

Source: Huynh J et al. Lenvatinib in patients with unresectable hepatocellular carcinoma who progressed to Child-Pugh B liver function. Ther Adv Med Oncol. 2022;14:17588359221116608 (Aug 24). Doi: 10.1177/17588359221116608

Key clinical point: Lenvatinib may continue to benefit patients with unresectable hepatocellular carcinoma (uHCC) despite liver function deterioration to Child-Pugh class B (CP-B) after therapy initiation.

Major finding: CP-B vs CP-A patients receiving lenvatinib had a median progression-free survival (PFS) and overall survival (OS) of 3.7 months (95% CI 1.8-7.4) vs 6.5 months (95% CI 5.6-7.4) and 6.8 months (95% CI 2.6-10.3) vs 13.3 months (95% CI 11.6-16.1), respectively. CP-B patients receiving sorafenib had a median PFS and OS of only 0.5 months (95% CI 0.1-3.6) and 4.5 months (95% CI 2.9-6.1, respectively. Lenvatinib showed no new safety signals in CP-B patients.

Study details: This post hoc analysis included patients with uHCC from the REFLECT trial whose liver function deteriorated to CP-B or remained CP-A within 8 weeks of randomization to lenvatinib (CP-B: n = 60; CP-A: n = 413) or sorafenib (CP-B: n = 47; CP-A: n = 427).

Disclosures: This study was funded by Eisai Inc. and Merck Sharp & Dohme (MSD) LLC. Some authors declared serving as speakers, consultants, or advisors for various organizations, including Eisai and MSD.

Source: Huynh J et al. Lenvatinib in patients with unresectable hepatocellular carcinoma who progressed to Child-Pugh B liver function. Ther Adv Med Oncol. 2022;14:17588359221116608 (Aug 24). Doi: 10.1177/17588359221116608

Key clinical point: Lenvatinib may continue to benefit patients with unresectable hepatocellular carcinoma (uHCC) despite liver function deterioration to Child-Pugh class B (CP-B) after therapy initiation.

Major finding: CP-B vs CP-A patients receiving lenvatinib had a median progression-free survival (PFS) and overall survival (OS) of 3.7 months (95% CI 1.8-7.4) vs 6.5 months (95% CI 5.6-7.4) and 6.8 months (95% CI 2.6-10.3) vs 13.3 months (95% CI 11.6-16.1), respectively. CP-B patients receiving sorafenib had a median PFS and OS of only 0.5 months (95% CI 0.1-3.6) and 4.5 months (95% CI 2.9-6.1, respectively. Lenvatinib showed no new safety signals in CP-B patients.

Study details: This post hoc analysis included patients with uHCC from the REFLECT trial whose liver function deteriorated to CP-B or remained CP-A within 8 weeks of randomization to lenvatinib (CP-B: n = 60; CP-A: n = 413) or sorafenib (CP-B: n = 47; CP-A: n = 427).

Disclosures: This study was funded by Eisai Inc. and Merck Sharp & Dohme (MSD) LLC. Some authors declared serving as speakers, consultants, or advisors for various organizations, including Eisai and MSD.

Source: Huynh J et al. Lenvatinib in patients with unresectable hepatocellular carcinoma who progressed to Child-Pugh B liver function. Ther Adv Med Oncol. 2022;14:17588359221116608 (Aug 24). Doi: 10.1177/17588359221116608

Key clinical point: Sintilimab plus IBI305 (a bevacizumab biosimilar) exhibits a promising efficacy and safety profile in patients with advanced hepatocellular carcinoma (HCC).

Major finding: After a median follow-up of 17.8 months, the overall response rate was 34.0% (95% CI 20.0%-48.0%) and the median progression-free survival and overall survival were 10.5 months (95% CI 8.3-12.7 months) and 20.2 months (95% CI 16.1-24.3 months), respectively. The grade 3-5 adverse event rate was 20.0%.

Study details: Findings are from a single-center phase 1b clinical trial that included 50 patients with advanced HCC who received sintilimab plus IBI305 every 3 weeks.

Disclosures: This study was partly supported by the Non-profit Central Research Institution Fund of the Chinese Academy of Medical Sciences. The authors declared no conflicts of interest.

Source: Zhang W et al. Serum concentration of CD137 and tumor infiltration by M1 macrophages predict the response to sintilimab plus bevacizumab biosimilar in advanced hepatocellular carcinoma patients. Clin Cancer Res. 2022;28(16):3499-3508 (Aug 15). Doi: 10.1158/1078-0432.CCR-21-3972

Key clinical point: Sintilimab plus IBI305 (a bevacizumab biosimilar) exhibits a promising efficacy and safety profile in patients with advanced hepatocellular carcinoma (HCC).

Major finding: After a median follow-up of 17.8 months, the overall response rate was 34.0% (95% CI 20.0%-48.0%) and the median progression-free survival and overall survival were 10.5 months (95% CI 8.3-12.7 months) and 20.2 months (95% CI 16.1-24.3 months), respectively. The grade 3-5 adverse event rate was 20.0%.

Study details: Findings are from a single-center phase 1b clinical trial that included 50 patients with advanced HCC who received sintilimab plus IBI305 every 3 weeks.

Disclosures: This study was partly supported by the Non-profit Central Research Institution Fund of the Chinese Academy of Medical Sciences. The authors declared no conflicts of interest.

Source: Zhang W et al. Serum concentration of CD137 and tumor infiltration by M1 macrophages predict the response to sintilimab plus bevacizumab biosimilar in advanced hepatocellular carcinoma patients. Clin Cancer Res. 2022;28(16):3499-3508 (Aug 15). Doi: 10.1158/1078-0432.CCR-21-3972

Key clinical point: Sintilimab plus IBI305 (a bevacizumab biosimilar) exhibits a promising efficacy and safety profile in patients with advanced hepatocellular carcinoma (HCC).

Major finding: After a median follow-up of 17.8 months, the overall response rate was 34.0% (95% CI 20.0%-48.0%) and the median progression-free survival and overall survival were 10.5 months (95% CI 8.3-12.7 months) and 20.2 months (95% CI 16.1-24.3 months), respectively. The grade 3-5 adverse event rate was 20.0%.

Study details: Findings are from a single-center phase 1b clinical trial that included 50 patients with advanced HCC who received sintilimab plus IBI305 every 3 weeks.

Disclosures: This study was partly supported by the Non-profit Central Research Institution Fund of the Chinese Academy of Medical Sciences. The authors declared no conflicts of interest.

Source: Zhang W et al. Serum concentration of CD137 and tumor infiltration by M1 macrophages predict the response to sintilimab plus bevacizumab biosimilar in advanced hepatocellular carcinoma patients. Clin Cancer Res. 2022;28(16):3499-3508 (Aug 15). Doi: 10.1158/1078-0432.CCR-21-3972

Key clinical point: Several preoperative and postoperative factors predict the risk for arm lymphedema in patients who undergo breast cancer (BC) surgery.

Major finding: Young age (<60 years; P < .001), high body mass index (P < .001), advanced preoperative T and N classifications (P ≤ .01), total mastectomy (P < .001), axillary dissection (P < .001), and collagen disease (P = .024) were the preoperative risk factors for lymphedema. Postoperative bleeding (P   =   .017), chemotherapy (P < .001), and radiotherapy (P < .001) were among the postoperative risk factors for lymphedema.

Study details: Findings are from a nationwide retrospective cohort study including 84,022 women who underwent BC surgery, of which 1547 patients received treatments for lymphedema.

Disclosures: This work was supported by the Ministry of Health, Labour and Welfare, Japan, and other sources. N Michihata declared serving as an employee at The University of Tokyo.

Source: Konishi T et al. Risk factors for arm lymphedema following breast cancer surgery: A Japanese nationwide database study of 84,022 patients. Breast Cancer. 2022 (Aug 23). Doi: 10.1007/s12282-022-01395-5.

Key clinical point: Several preoperative and postoperative factors predict the risk for arm lymphedema in patients who undergo breast cancer (BC) surgery.

Major finding: Young age (<60 years; P < .001), high body mass index (P < .001), advanced preoperative T and N classifications (P ≤ .01), total mastectomy (P < .001), axillary dissection (P < .001), and collagen disease (P = .024) were the preoperative risk factors for lymphedema. Postoperative bleeding (P   =   .017), chemotherapy (P < .001), and radiotherapy (P < .001) were among the postoperative risk factors for lymphedema.

Study details: Findings are from a nationwide retrospective cohort study including 84,022 women who underwent BC surgery, of which 1547 patients received treatments for lymphedema.

Disclosures: This work was supported by the Ministry of Health, Labour and Welfare, Japan, and other sources. N Michihata declared serving as an employee at The University of Tokyo.

Source: Konishi T et al. Risk factors for arm lymphedema following breast cancer surgery: A Japanese nationwide database study of 84,022 patients. Breast Cancer. 2022 (Aug 23). Doi: 10.1007/s12282-022-01395-5.

Key clinical point: Several preoperative and postoperative factors predict the risk for arm lymphedema in patients who undergo breast cancer (BC) surgery.

Major finding: Young age (<60 years; P < .001), high body mass index (P < .001), advanced preoperative T and N classifications (P ≤ .01), total mastectomy (P < .001), axillary dissection (P < .001), and collagen disease (P = .024) were the preoperative risk factors for lymphedema. Postoperative bleeding (P   =   .017), chemotherapy (P < .001), and radiotherapy (P < .001) were among the postoperative risk factors for lymphedema.

Study details: Findings are from a nationwide retrospective cohort study including 84,022 women who underwent BC surgery, of which 1547 patients received treatments for lymphedema.

Disclosures: This work was supported by the Ministry of Health, Labour and Welfare, Japan, and other sources. N Michihata declared serving as an employee at The University of Tokyo.

Source: Konishi T et al. Risk factors for arm lymphedema following breast cancer surgery: A Japanese nationwide database study of 84,022 patients. Breast Cancer. 2022 (Aug 23). Doi: 10.1007/s12282-022-01395-5.

Key clinical point: Letrozole-associated controlled ovarian hyperstimulation (LetCOH) was as effective as conventional controlled ovarian hyperstimulation (cCOH) for fertility preservation (FP) and minimized the risk for supraphysiologic estrogen exposure; however, more patients in the LetCOH group relapsed.

Major finding: In the LetCOH vs cCOH group, estradiol peak at the ovulation trigger was lower, but oocyte maturation rates were significantly higher (P < .001), and the final number of mature oocytes collected was comparable (P   =   .281). Disease recurrence occurred in 17% and 7.2% of patients in the LetCOH and cCOH groups, respectively.

Study details: Findings are from a retrospective observational study including 97 patients with nonmetastatic breast cancer (BC) who were ≤ 40 years old and had undergone FP with LetCOH (n = 41) or cCOH (n = 56) before receiving chemotherapy.

Disclosures: This study did not receive any funding. I Demeestere declared receiving honoraria and support and serving as a consultant or advisor for several sources outside this work.

Source: Goldrat O et al. Efficacy and safety of controlled ovarian hyperstimulation with or without letrozole for fertility preservation in breast cancer patients: A multicenter retrospective study. Eur J Cancer. 2022;174:134-141 (Aug 20). Doi: 10.1016/j.ejca.2022.07.017

Key clinical point: Letrozole-associated controlled ovarian hyperstimulation (LetCOH) was as effective as conventional controlled ovarian hyperstimulation (cCOH) for fertility preservation (FP) and minimized the risk for supraphysiologic estrogen exposure; however, more patients in the LetCOH group relapsed.

Major finding: In the LetCOH vs cCOH group, estradiol peak at the ovulation trigger was lower, but oocyte maturation rates were significantly higher (P < .001), and the final number of mature oocytes collected was comparable (P   =   .281). Disease recurrence occurred in 17% and 7.2% of patients in the LetCOH and cCOH groups, respectively.

Study details: Findings are from a retrospective observational study including 97 patients with nonmetastatic breast cancer (BC) who were ≤ 40 years old and had undergone FP with LetCOH (n = 41) or cCOH (n = 56) before receiving chemotherapy.

Disclosures: This study did not receive any funding. I Demeestere declared receiving honoraria and support and serving as a consultant or advisor for several sources outside this work.

Source: Goldrat O et al. Efficacy and safety of controlled ovarian hyperstimulation with or without letrozole for fertility preservation in breast cancer patients: A multicenter retrospective study. Eur J Cancer. 2022;174:134-141 (Aug 20). Doi: 10.1016/j.ejca.2022.07.017

Key clinical point: Letrozole-associated controlled ovarian hyperstimulation (LetCOH) was as effective as conventional controlled ovarian hyperstimulation (cCOH) for fertility preservation (FP) and minimized the risk for supraphysiologic estrogen exposure; however, more patients in the LetCOH group relapsed.

Major finding: In the LetCOH vs cCOH group, estradiol peak at the ovulation trigger was lower, but oocyte maturation rates were significantly higher (P < .001), and the final number of mature oocytes collected was comparable (P   =   .281). Disease recurrence occurred in 17% and 7.2% of patients in the LetCOH and cCOH groups, respectively.

Study details: Findings are from a retrospective observational study including 97 patients with nonmetastatic breast cancer (BC) who were ≤ 40 years old and had undergone FP with LetCOH (n = 41) or cCOH (n = 56) before receiving chemotherapy.

Disclosures: This study did not receive any funding. I Demeestere declared receiving honoraria and support and serving as a consultant or advisor for several sources outside this work.

Source: Goldrat O et al. Efficacy and safety of controlled ovarian hyperstimulation with or without letrozole for fertility preservation in breast cancer patients: A multicenter retrospective study. Eur J Cancer. 2022;174:134-141 (Aug 20). Doi: 10.1016/j.ejca.2022.07.017

Key clinical point: Women who were diagnosed with breast cancer (BC) at a young age and underwent fertility preservation (FP) did not experience any increased risk for disease-specific mortality or relapse.

Major finding: Compared with women who did not undergo FP, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR] 0.59; 95% CI 0.32-1.09) and nonhormonal FP (aHR 0.51; 95% CI 0.20-1.29). Hormonal (aHR 0.81; 95% CI 0.49-1.37) and nonhormonal (aHR 0.75; 95% CI 0.35-1.62) FP were associated with similar relapse or death rates in a subcohort of 723 women with complete relapse information.

Study details: Findings are from an analysis of a population-based nationwide cohort study including 1275 women of reproductive age (18-44 years old) who were diagnosed with BC, of which 425 women received hormonal (n = 367) or nonhormonal (n = 58) FP treatment.

Disclosures: This study was supported by the Swedish Cancer Society and other sources. Prof. Bergh declared receiving grants and personal fees from several sources.

Source: Marklund A et al. Relapse rates and disease-specific mortality following procedures for fertility preservation at time of breast cancer diagnosis. JAMA Oncol. 2022 (Aug 25). Doi: 10.1001/jamaoncol.2022.3677

Key clinical point: Women who were diagnosed with breast cancer (BC) at a young age and underwent fertility preservation (FP) did not experience any increased risk for disease-specific mortality or relapse.

Major finding: Compared with women who did not undergo FP, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR] 0.59; 95% CI 0.32-1.09) and nonhormonal FP (aHR 0.51; 95% CI 0.20-1.29). Hormonal (aHR 0.81; 95% CI 0.49-1.37) and nonhormonal (aHR 0.75; 95% CI 0.35-1.62) FP were associated with similar relapse or death rates in a subcohort of 723 women with complete relapse information.

Study details: Findings are from an analysis of a population-based nationwide cohort study including 1275 women of reproductive age (18-44 years old) who were diagnosed with BC, of which 425 women received hormonal (n = 367) or nonhormonal (n = 58) FP treatment.

Disclosures: This study was supported by the Swedish Cancer Society and other sources. Prof. Bergh declared receiving grants and personal fees from several sources.

Source: Marklund A et al. Relapse rates and disease-specific mortality following procedures for fertility preservation at time of breast cancer diagnosis. JAMA Oncol. 2022 (Aug 25). Doi: 10.1001/jamaoncol.2022.3677

Key clinical point: Women who were diagnosed with breast cancer (BC) at a young age and underwent fertility preservation (FP) did not experience any increased risk for disease-specific mortality or relapse.

Major finding: Compared with women who did not undergo FP, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR] 0.59; 95% CI 0.32-1.09) and nonhormonal FP (aHR 0.51; 95% CI 0.20-1.29). Hormonal (aHR 0.81; 95% CI 0.49-1.37) and nonhormonal (aHR 0.75; 95% CI 0.35-1.62) FP were associated with similar relapse or death rates in a subcohort of 723 women with complete relapse information.

Study details: Findings are from an analysis of a population-based nationwide cohort study including 1275 women of reproductive age (18-44 years old) who were diagnosed with BC, of which 425 women received hormonal (n = 367) or nonhormonal (n = 58) FP treatment.

Disclosures: This study was supported by the Swedish Cancer Society and other sources. Prof. Bergh declared receiving grants and personal fees from several sources.

Source: Marklund A et al. Relapse rates and disease-specific mortality following procedures for fertility preservation at time of breast cancer diagnosis. JAMA Oncol. 2022 (Aug 25). Doi: 10.1001/jamaoncol.2022.3677

Key clinical point: In estrogen receptor-positive/human epidermal growth factor receptor-positive (ER+/HER2+) breast cancer (BC), HER2-enriched (HER2-E) tumors were more likely to respond poorly to aromatase inhibitor (AI) therapy and pose an increased risk for disease recurrence.

Major finding: AI-treated HER2-E tumors were associated with poorer Ki67 response and higher Ki67 expression level at 2-weeks timepoint compared with luminal A and B tumors (odds ratio 1.52-12.31; false discovery rate < 0.0001). HER2-E subtype was an independent predictor of shorter time to recurrence (hazard ratio 2.55; P   =   .022).

Study details: Findings are from the phase 3 POETIC trial including 342 patients with early ER+/HER2+ BC who were assigned to 2 weeks of perisurgical AI (n = 237) or no AI (n = 105).

Disclosures: This study was funded by Cancer Research UK. Some authors declared holding or filing patents or receiving grants, nonfinancial support, consulting fees, honoraria, or research funding from several sources.

Source: Bergamino MA et al. HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer. EBioMedicine. 2022;83:104205 (Aug 16). Doi: 10.1016/j.ebiom.2022.104205

Key clinical point: In estrogen receptor-positive/human epidermal growth factor receptor-positive (ER+/HER2+) breast cancer (BC), HER2-enriched (HER2-E) tumors were more likely to respond poorly to aromatase inhibitor (AI) therapy and pose an increased risk for disease recurrence.

Major finding: AI-treated HER2-E tumors were associated with poorer Ki67 response and higher Ki67 expression level at 2-weeks timepoint compared with luminal A and B tumors (odds ratio 1.52-12.31; false discovery rate < 0.0001). HER2-E subtype was an independent predictor of shorter time to recurrence (hazard ratio 2.55; P   =   .022).

Study details: Findings are from the phase 3 POETIC trial including 342 patients with early ER+/HER2+ BC who were assigned to 2 weeks of perisurgical AI (n = 237) or no AI (n = 105).

Disclosures: This study was funded by Cancer Research UK. Some authors declared holding or filing patents or receiving grants, nonfinancial support, consulting fees, honoraria, or research funding from several sources.

Source: Bergamino MA et al. HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer. EBioMedicine. 2022;83:104205 (Aug 16). Doi: 10.1016/j.ebiom.2022.104205

Key clinical point: In estrogen receptor-positive/human epidermal growth factor receptor-positive (ER+/HER2+) breast cancer (BC), HER2-enriched (HER2-E) tumors were more likely to respond poorly to aromatase inhibitor (AI) therapy and pose an increased risk for disease recurrence.

Major finding: AI-treated HER2-E tumors were associated with poorer Ki67 response and higher Ki67 expression level at 2-weeks timepoint compared with luminal A and B tumors (odds ratio 1.52-12.31; false discovery rate < 0.0001). HER2-E subtype was an independent predictor of shorter time to recurrence (hazard ratio 2.55; P   =   .022).

Study details: Findings are from the phase 3 POETIC trial including 342 patients with early ER+/HER2+ BC who were assigned to 2 weeks of perisurgical AI (n = 237) or no AI (n = 105).

Disclosures: This study was funded by Cancer Research UK. Some authors declared holding or filing patents or receiving grants, nonfinancial support, consulting fees, honoraria, or research funding from several sources.

Source: Bergamino MA et al. HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer. EBioMedicine. 2022;83:104205 (Aug 16). Doi: 10.1016/j.ebiom.2022.104205

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (ERBB2+) and triple-negative breast cancer (TNBC) are more likely to need radiation for brain metastasis (BRM) than those with other BC subtypes.

Major finding: At the 3-year timepoint, the cumulative incidences of BRM was highest in patients with ERBB2+/hormone receptor-negative (HR−) BC (25.3%). TNBC (hazard ratio 4.25), ERBB2+/HR+ BC (hazard ratio 1.94), and ERBB2+/HR− BC (hazard ratio 2.81; all P < .001) were associated with a shorter time from BC diagnosis to brain radiotherapy than HR+/ERBB2− BC. Patients who received radiotherapy for BRM were more likely to have TNBC or ERBB2+ BC than HR+/ERBB2− BC (P < .001).

Study details: Findings are from a retrospective, observational population-based cohort study including 3916 patients with metastatic BC, of which 31.0% had HR+/ERBB2− BC, 7.9% had ERBB2+/HR+ BC, 5.1% had ERBB2+/HR− BC, and 6.6% had TNBC.

Disclosures: This research was supported by Eli Lilly. Some authors declared serving as consultants, board members, or speakers or receiving grants or personal fees from several sources, including Eli Lilly.

Source: Wang XY et al. Analysis of rates of brain metastases and association with breast cancer subtypes in Ontario, Canada. JAMA Netw Open. 2022;5(8):e2225424 (Aug 12). Doi: 10.1001/jamanetworkopen.2022.25424

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (ERBB2+) and triple-negative breast cancer (TNBC) are more likely to need radiation for brain metastasis (BRM) than those with other BC subtypes.

Major finding: At the 3-year timepoint, the cumulative incidences of BRM was highest in patients with ERBB2+/hormone receptor-negative (HR−) BC (25.3%). TNBC (hazard ratio 4.25), ERBB2+/HR+ BC (hazard ratio 1.94), and ERBB2+/HR− BC (hazard ratio 2.81; all P < .001) were associated with a shorter time from BC diagnosis to brain radiotherapy than HR+/ERBB2− BC. Patients who received radiotherapy for BRM were more likely to have TNBC or ERBB2+ BC than HR+/ERBB2− BC (P < .001).

Study details: Findings are from a retrospective, observational population-based cohort study including 3916 patients with metastatic BC, of which 31.0% had HR+/ERBB2− BC, 7.9% had ERBB2+/HR+ BC, 5.1% had ERBB2+/HR− BC, and 6.6% had TNBC.

Disclosures: This research was supported by Eli Lilly. Some authors declared serving as consultants, board members, or speakers or receiving grants or personal fees from several sources, including Eli Lilly.

Source: Wang XY et al. Analysis of rates of brain metastases and association with breast cancer subtypes in Ontario, Canada. JAMA Netw Open. 2022;5(8):e2225424 (Aug 12). Doi: 10.1001/jamanetworkopen.2022.25424

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (ERBB2+) and triple-negative breast cancer (TNBC) are more likely to need radiation for brain metastasis (BRM) than those with other BC subtypes.

Major finding: At the 3-year timepoint, the cumulative incidences of BRM was highest in patients with ERBB2+/hormone receptor-negative (HR−) BC (25.3%). TNBC (hazard ratio 4.25), ERBB2+/HR+ BC (hazard ratio 1.94), and ERBB2+/HR− BC (hazard ratio 2.81; all P < .001) were associated with a shorter time from BC diagnosis to brain radiotherapy than HR+/ERBB2− BC. Patients who received radiotherapy for BRM were more likely to have TNBC or ERBB2+ BC than HR+/ERBB2− BC (P < .001).

Study details: Findings are from a retrospective, observational population-based cohort study including 3916 patients with metastatic BC, of which 31.0% had HR+/ERBB2− BC, 7.9% had ERBB2+/HR+ BC, 5.1% had ERBB2+/HR− BC, and 6.6% had TNBC.

Disclosures: This research was supported by Eli Lilly. Some authors declared serving as consultants, board members, or speakers or receiving grants or personal fees from several sources, including Eli Lilly.

Source: Wang XY et al. Analysis of rates of brain metastases and association with breast cancer subtypes in Ontario, Canada. JAMA Netw Open. 2022;5(8):e2225424 (Aug 12). Doi: 10.1001/jamanetworkopen.2022.25424

Additional hidradenitis suppurativa (HS) treatments could be on the horizon with the news that both secukinumab and the investigational drug brepocitinib reduced the effects of the chronic and painful skin condition in separate trials.

Around 40%-50% of patients exhibited a clinical response to these agents at 16 weeks, a leading HS expert reported at the annual congress of the European Academy of Dermatology and Venereology.
 

Time in the spotlight for HS

Research into HS is “an incredibly active field at this moment,” said Alexa B. Kimball, MD, MPH, professor of dermatology, Harvard Medical School, and president and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, Boston.

It’s “been great for advancing our understanding of the biology and the treatments that we will be able to use,” she said.

During the late-breaking sessions at the annual EADV Congress, Dr. Kimball presented data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety and tolerability of the interleukin (IL) 17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS.

“This is only the second phase 3 program we have ever seen in HS and the first one since 2016,” Dr. Kimball said of the trials. It’s also the largest trial program in HS conducted to date, she added, “so it really is a milestone.”

The last big development was when adalimumab, a tumor necrosis factor (TNF) blocker, gained regulatory approval for HS in 2016, observed Neil Patel, PhD, MRCP, who leads the HS service at Imperial College Healthcare NHS Trust in London.

“Adalimumab has been very helpful for many patients, but not all patients respond, and others may respond initially but then the treatment starts to fail after a year or 2,” Dr. Patel said in an interview with this news organization.

“There is definitely a huge need for alternative medication for this condition, which still has a lack of effective treatment options,” added Dr. Patel, who was not involved in either of the studies.

“One major upside for secukinumab is that its safety profile is generally very good and familiarity in the dermatologic community is already well established,” Christopher Sayed, MD, said in a separate interview.

“This will make most providers very comfortable offering it as a potential treatment option sooner rather than later given that its efficacy has now been demonstrated in phase 3 trials,” added Dr. Sayed, associate professor of dermatology at the University of North Carolina at Chapel Hill.
 

Two identically designed trials

Altogether, SUNSHINE and SUNRISE enrolled just over 1,000 patients at 219 sites in 33 countries. Both trials were identical in their design: A 4-week run-in phase before a randomized, double-blind treatment phase that tested two dosing regimens of secukinumab (300 mg administered subcutaneously) every 2 or 4 weeks vs. placebo for 16 weeks. The trial continued after this time, with patients in the placebo arm re–randomly assigned to treatment with one of the two secukinumab regimens out to a year.

The primary endpoint was the percentage of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR) after 16 weeks of treatment, with key secondary endpoints, which were abscess and inflammatory nodule (AN) count, occurrence of flares, and at least a 30% reduction in Patient’s Global Assessment of Skin Pain assessed using a numeric rating scale (NPRS30).
 

Secukinumab superior to placebo

The HiSCR is defined as at least a 50% decrease in AN count with no increase in the number of abscesses or in the number of draining fistulas relative to baseline. This was achieved by about 42%-45% of patients who received secukinumab every 2 weeks, about 42%-46% of those who received secukinumab every 4 weeks, and about 31%-33% of those on placebo in both studies.

Of note, fewer patients treated with secukinumab (about 15%-20% among those treated every 2 weeks, and about 15% to 23% among those treated every 4 weeks) than those on placebo (27%-29%) experienced flares, defined as at least a 25% increase in AN count and at least a two-point increase relative to baseline values.

Improvement in HS pain can be a difficult parameter to meet, Dr. Kimball noted. “Pain is such an important feature of this disease as it so debilitating for the patients.” More than one-third (almost 36%-39%) of patients given secukinumab vs. just over a quarter (26.9%) given placebo achieved at least a 30% reduction in NPRS30 ratings, she reported. The difference between active and placebo treatment was significant only when secukinumab was given every 2 weeks, however.

“The placebo rates that we see in these studies are exactly parallel to what we saw in other studies, and other disease states when we had a 50% bar of improvement,” Dr. Kimball said when questioned about these results.

“HS is a highly variable disease; it’s maybe not so much the placebo rate or the scoring system used but maybe the 50% bar set for improvement is too low. It’s likely, as data start to mature and a 75% HiSCR can be calculated, that the placebo rates will drop,” she said.

There were no surprises when it came to the safety of secukinumab, being an old player in a new game, she noted. It was “well tolerated” and tolerability was “consistent with the known safety profile,” Dr. Kimball said, “so we expect it to be a new, safe, and effective add to our armamentarium in treating this disease.”

This research involves “basically borrowing drugs from other areas and trying them in HS to see what effect they may have,” Dr. Patel said, noting that drugs such as adalimumab and secukinumab already had a proven track record in other diseases, such as psoriasis. “These early data for secukinumab definitely are very exciting, but we would need to see real-life results” in patients with HS who are not enrolled in trials to see the benefits, he added.

‘Tipping point’ for HS research

“I think we will look back on this meeting and realize that it was an incredibly important tipping point for the treatment of this incredibly debilitating disease,” Dr. Kimball said.

Elsewhere at the meeting, she had presented findings from a phase 2a study that pitted three different kinase inhibitors with different modes of action against each other and compared them with placebo. 

The three agents evaluated are an IL-1 receptor–associated kinase 4 inhibitor known as PF-06650833, a tyrosine kinase 2 (TYK2) JAK1 inhibitor brepocitinib, and the TYK2 inhibitor PF-06826647.

“This technique has been used in oncology,” Dr. Kimball said, noting that the ability to test multiple drugs at the same time “means we can really much more efficiently test two different things at the same time, and also put fewer patients at risk for potential problems if drugs don’t work.”
 

Positive signs for brepocitinib, not the other kinases tested

The results showed that though brepocitinib worked in HS, the other two novel compounds did not appear to have beneficial effects. Just over half (52%) of the 52 patients treated with brepocitinib achieved an HiSCR at 16 weeks, compared with around one-third of those given placebo, PF-06650833, or PF-06826647.

A similar benefit was seen in terms of reduction in flares for brepocitinib but not the other agents, although there was no difference between them all in terms of NPRS30 pain reduction.

“We’ve been able to test three different modalities. This tells us some things about the pathophysiology for HS, which is a very profoundly intensive inflammatory process,” which, Dr. Kimball said, “may require multiple modalities of action to get it under control.” In addition, these “general modalities seem to safe and well tolerated,” she added.
 

Take-homes for practice and future research

“While it is disappointing that two of the drugs tested did not clearly demonstrate efficacy, it is very possible that these mechanisms of action may be successful targets in the future as new dosing strategies and drugs targeting these pathways are developed,” Dr. Sayed said.

A case in point, he added, was that “adalimumab did not meet treatment endpoints at a dose of 40 mg every other week, but clearly has made a major impact at 40 mg weekly.”

The bottom line is that “both secukinumab and beprocitinib demonstrated efficacy over placebo and are likely to be helpful for a significant number of patients with HS,” Dr. Sayed said. “Hopefully, we’ll see head-to-head trials and more data regarding proportions of patients with deeper responses using criteria such as HiSCR75 and HiSCR90.”

Moreover, “having a larger number of drugs with a range of mechanisms of action is extraordinarily helpful given how difficult the disease can be to manage. We will hopefully continue to see creative approaches and further successes in the current wave of phase 1, 2, and 3 trials that are already underway.”

The SUNSHINE and SUNRISE studies were funded by Novartis Pharma AG, Basel, Switzerland. The phase 2A study Dr. Kimball presented was sponsored by Pfizer.

Dr. Kimball disclosed ties to both Novartis and Pfizer and acts as a consultant and investigator to AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, and UCB. She is an investigator for Incyte and AnaptysBio; acts as a consultant to Bayer, Boehringer Ingelheim, Ventyz, Moonlake, Lily, Concert, EvoImmune, Sonoma Bio, and Sanofi; receives fellowship funding from Janssen, and serves on the Board of Directors for Almirall.

Dr. Patel had no conflicts of interest to disclose. Dr. Sayed is the director of the HS Foundation, a nonprofit organization, and has acted as an adviser or consultant to, speaker for, and received research funding from multiple drug companies including AbbVie, ChemoCentryx, Incyte, InflaRx, Novartis, and UCB.

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

Additional hidradenitis suppurativa (HS) treatments could be on the horizon with the news that both secukinumab and the investigational drug brepocitinib reduced the effects of the chronic and painful skin condition in separate trials.

Around 40%-50% of patients exhibited a clinical response to these agents at 16 weeks, a leading HS expert reported at the annual congress of the European Academy of Dermatology and Venereology.
 

Time in the spotlight for HS

Research into HS is “an incredibly active field at this moment,” said Alexa B. Kimball, MD, MPH, professor of dermatology, Harvard Medical School, and president and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, Boston.

It’s “been great for advancing our understanding of the biology and the treatments that we will be able to use,” she said.

During the late-breaking sessions at the annual EADV Congress, Dr. Kimball presented data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety and tolerability of the interleukin (IL) 17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS.

“This is only the second phase 3 program we have ever seen in HS and the first one since 2016,” Dr. Kimball said of the trials. It’s also the largest trial program in HS conducted to date, she added, “so it really is a milestone.”

The last big development was when adalimumab, a tumor necrosis factor (TNF) blocker, gained regulatory approval for HS in 2016, observed Neil Patel, PhD, MRCP, who leads the HS service at Imperial College Healthcare NHS Trust in London.

“Adalimumab has been very helpful for many patients, but not all patients respond, and others may respond initially but then the treatment starts to fail after a year or 2,” Dr. Patel said in an interview with this news organization.

“There is definitely a huge need for alternative medication for this condition, which still has a lack of effective treatment options,” added Dr. Patel, who was not involved in either of the studies.

“One major upside for secukinumab is that its safety profile is generally very good and familiarity in the dermatologic community is already well established,” Christopher Sayed, MD, said in a separate interview.

“This will make most providers very comfortable offering it as a potential treatment option sooner rather than later given that its efficacy has now been demonstrated in phase 3 trials,” added Dr. Sayed, associate professor of dermatology at the University of North Carolina at Chapel Hill.
 

Two identically designed trials

Altogether, SUNSHINE and SUNRISE enrolled just over 1,000 patients at 219 sites in 33 countries. Both trials were identical in their design: A 4-week run-in phase before a randomized, double-blind treatment phase that tested two dosing regimens of secukinumab (300 mg administered subcutaneously) every 2 or 4 weeks vs. placebo for 16 weeks. The trial continued after this time, with patients in the placebo arm re–randomly assigned to treatment with one of the two secukinumab regimens out to a year.

The primary endpoint was the percentage of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR) after 16 weeks of treatment, with key secondary endpoints, which were abscess and inflammatory nodule (AN) count, occurrence of flares, and at least a 30% reduction in Patient’s Global Assessment of Skin Pain assessed using a numeric rating scale (NPRS30).
 

Secukinumab superior to placebo

The HiSCR is defined as at least a 50% decrease in AN count with no increase in the number of abscesses or in the number of draining fistulas relative to baseline. This was achieved by about 42%-45% of patients who received secukinumab every 2 weeks, about 42%-46% of those who received secukinumab every 4 weeks, and about 31%-33% of those on placebo in both studies.

Of note, fewer patients treated with secukinumab (about 15%-20% among those treated every 2 weeks, and about 15% to 23% among those treated every 4 weeks) than those on placebo (27%-29%) experienced flares, defined as at least a 25% increase in AN count and at least a two-point increase relative to baseline values.

Improvement in HS pain can be a difficult parameter to meet, Dr. Kimball noted. “Pain is such an important feature of this disease as it so debilitating for the patients.” More than one-third (almost 36%-39%) of patients given secukinumab vs. just over a quarter (26.9%) given placebo achieved at least a 30% reduction in NPRS30 ratings, she reported. The difference between active and placebo treatment was significant only when secukinumab was given every 2 weeks, however.

“The placebo rates that we see in these studies are exactly parallel to what we saw in other studies, and other disease states when we had a 50% bar of improvement,” Dr. Kimball said when questioned about these results.

“HS is a highly variable disease; it’s maybe not so much the placebo rate or the scoring system used but maybe the 50% bar set for improvement is too low. It’s likely, as data start to mature and a 75% HiSCR can be calculated, that the placebo rates will drop,” she said.

There were no surprises when it came to the safety of secukinumab, being an old player in a new game, she noted. It was “well tolerated” and tolerability was “consistent with the known safety profile,” Dr. Kimball said, “so we expect it to be a new, safe, and effective add to our armamentarium in treating this disease.”

This research involves “basically borrowing drugs from other areas and trying them in HS to see what effect they may have,” Dr. Patel said, noting that drugs such as adalimumab and secukinumab already had a proven track record in other diseases, such as psoriasis. “These early data for secukinumab definitely are very exciting, but we would need to see real-life results” in patients with HS who are not enrolled in trials to see the benefits, he added.

‘Tipping point’ for HS research

“I think we will look back on this meeting and realize that it was an incredibly important tipping point for the treatment of this incredibly debilitating disease,” Dr. Kimball said.

Elsewhere at the meeting, she had presented findings from a phase 2a study that pitted three different kinase inhibitors with different modes of action against each other and compared them with placebo. 

The three agents evaluated are an IL-1 receptor–associated kinase 4 inhibitor known as PF-06650833, a tyrosine kinase 2 (TYK2) JAK1 inhibitor brepocitinib, and the TYK2 inhibitor PF-06826647.

“This technique has been used in oncology,” Dr. Kimball said, noting that the ability to test multiple drugs at the same time “means we can really much more efficiently test two different things at the same time, and also put fewer patients at risk for potential problems if drugs don’t work.”
 

Positive signs for brepocitinib, not the other kinases tested

The results showed that though brepocitinib worked in HS, the other two novel compounds did not appear to have beneficial effects. Just over half (52%) of the 52 patients treated with brepocitinib achieved an HiSCR at 16 weeks, compared with around one-third of those given placebo, PF-06650833, or PF-06826647.

A similar benefit was seen in terms of reduction in flares for brepocitinib but not the other agents, although there was no difference between them all in terms of NPRS30 pain reduction.

“We’ve been able to test three different modalities. This tells us some things about the pathophysiology for HS, which is a very profoundly intensive inflammatory process,” which, Dr. Kimball said, “may require multiple modalities of action to get it under control.” In addition, these “general modalities seem to safe and well tolerated,” she added.
 

Take-homes for practice and future research

“While it is disappointing that two of the drugs tested did not clearly demonstrate efficacy, it is very possible that these mechanisms of action may be successful targets in the future as new dosing strategies and drugs targeting these pathways are developed,” Dr. Sayed said.

A case in point, he added, was that “adalimumab did not meet treatment endpoints at a dose of 40 mg every other week, but clearly has made a major impact at 40 mg weekly.”

The bottom line is that “both secukinumab and beprocitinib demonstrated efficacy over placebo and are likely to be helpful for a significant number of patients with HS,” Dr. Sayed said. “Hopefully, we’ll see head-to-head trials and more data regarding proportions of patients with deeper responses using criteria such as HiSCR75 and HiSCR90.”

Moreover, “having a larger number of drugs with a range of mechanisms of action is extraordinarily helpful given how difficult the disease can be to manage. We will hopefully continue to see creative approaches and further successes in the current wave of phase 1, 2, and 3 trials that are already underway.”

The SUNSHINE and SUNRISE studies were funded by Novartis Pharma AG, Basel, Switzerland. The phase 2A study Dr. Kimball presented was sponsored by Pfizer.

Dr. Kimball disclosed ties to both Novartis and Pfizer and acts as a consultant and investigator to AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, and UCB. She is an investigator for Incyte and AnaptysBio; acts as a consultant to Bayer, Boehringer Ingelheim, Ventyz, Moonlake, Lily, Concert, EvoImmune, Sonoma Bio, and Sanofi; receives fellowship funding from Janssen, and serves on the Board of Directors for Almirall.

Dr. Patel had no conflicts of interest to disclose. Dr. Sayed is the director of the HS Foundation, a nonprofit organization, and has acted as an adviser or consultant to, speaker for, and received research funding from multiple drug companies including AbbVie, ChemoCentryx, Incyte, InflaRx, Novartis, and UCB.

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

Additional hidradenitis suppurativa (HS) treatments could be on the horizon with the news that both secukinumab and the investigational drug brepocitinib reduced the effects of the chronic and painful skin condition in separate trials.

Around 40%-50% of patients exhibited a clinical response to these agents at 16 weeks, a leading HS expert reported at the annual congress of the European Academy of Dermatology and Venereology.
 

Time in the spotlight for HS

Research into HS is “an incredibly active field at this moment,” said Alexa B. Kimball, MD, MPH, professor of dermatology, Harvard Medical School, and president and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, Boston.

It’s “been great for advancing our understanding of the biology and the treatments that we will be able to use,” she said.

During the late-breaking sessions at the annual EADV Congress, Dr. Kimball presented data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety and tolerability of the interleukin (IL) 17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS.

“This is only the second phase 3 program we have ever seen in HS and the first one since 2016,” Dr. Kimball said of the trials. It’s also the largest trial program in HS conducted to date, she added, “so it really is a milestone.”

The last big development was when adalimumab, a tumor necrosis factor (TNF) blocker, gained regulatory approval for HS in 2016, observed Neil Patel, PhD, MRCP, who leads the HS service at Imperial College Healthcare NHS Trust in London.

“Adalimumab has been very helpful for many patients, but not all patients respond, and others may respond initially but then the treatment starts to fail after a year or 2,” Dr. Patel said in an interview with this news organization.

“There is definitely a huge need for alternative medication for this condition, which still has a lack of effective treatment options,” added Dr. Patel, who was not involved in either of the studies.

“One major upside for secukinumab is that its safety profile is generally very good and familiarity in the dermatologic community is already well established,” Christopher Sayed, MD, said in a separate interview.

“This will make most providers very comfortable offering it as a potential treatment option sooner rather than later given that its efficacy has now been demonstrated in phase 3 trials,” added Dr. Sayed, associate professor of dermatology at the University of North Carolina at Chapel Hill.
 

Two identically designed trials

Altogether, SUNSHINE and SUNRISE enrolled just over 1,000 patients at 219 sites in 33 countries. Both trials were identical in their design: A 4-week run-in phase before a randomized, double-blind treatment phase that tested two dosing regimens of secukinumab (300 mg administered subcutaneously) every 2 or 4 weeks vs. placebo for 16 weeks. The trial continued after this time, with patients in the placebo arm re–randomly assigned to treatment with one of the two secukinumab regimens out to a year.

The primary endpoint was the percentage of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR) after 16 weeks of treatment, with key secondary endpoints, which were abscess and inflammatory nodule (AN) count, occurrence of flares, and at least a 30% reduction in Patient’s Global Assessment of Skin Pain assessed using a numeric rating scale (NPRS30).
 

Secukinumab superior to placebo

The HiSCR is defined as at least a 50% decrease in AN count with no increase in the number of abscesses or in the number of draining fistulas relative to baseline. This was achieved by about 42%-45% of patients who received secukinumab every 2 weeks, about 42%-46% of those who received secukinumab every 4 weeks, and about 31%-33% of those on placebo in both studies.

Of note, fewer patients treated with secukinumab (about 15%-20% among those treated every 2 weeks, and about 15% to 23% among those treated every 4 weeks) than those on placebo (27%-29%) experienced flares, defined as at least a 25% increase in AN count and at least a two-point increase relative to baseline values.

Improvement in HS pain can be a difficult parameter to meet, Dr. Kimball noted. “Pain is such an important feature of this disease as it so debilitating for the patients.” More than one-third (almost 36%-39%) of patients given secukinumab vs. just over a quarter (26.9%) given placebo achieved at least a 30% reduction in NPRS30 ratings, she reported. The difference between active and placebo treatment was significant only when secukinumab was given every 2 weeks, however.

“The placebo rates that we see in these studies are exactly parallel to what we saw in other studies, and other disease states when we had a 50% bar of improvement,” Dr. Kimball said when questioned about these results.

“HS is a highly variable disease; it’s maybe not so much the placebo rate or the scoring system used but maybe the 50% bar set for improvement is too low. It’s likely, as data start to mature and a 75% HiSCR can be calculated, that the placebo rates will drop,” she said.

There were no surprises when it came to the safety of secukinumab, being an old player in a new game, she noted. It was “well tolerated” and tolerability was “consistent with the known safety profile,” Dr. Kimball said, “so we expect it to be a new, safe, and effective add to our armamentarium in treating this disease.”

This research involves “basically borrowing drugs from other areas and trying them in HS to see what effect they may have,” Dr. Patel said, noting that drugs such as adalimumab and secukinumab already had a proven track record in other diseases, such as psoriasis. “These early data for secukinumab definitely are very exciting, but we would need to see real-life results” in patients with HS who are not enrolled in trials to see the benefits, he added.

‘Tipping point’ for HS research

“I think we will look back on this meeting and realize that it was an incredibly important tipping point for the treatment of this incredibly debilitating disease,” Dr. Kimball said.

Elsewhere at the meeting, she had presented findings from a phase 2a study that pitted three different kinase inhibitors with different modes of action against each other and compared them with placebo. 

The three agents evaluated are an IL-1 receptor–associated kinase 4 inhibitor known as PF-06650833, a tyrosine kinase 2 (TYK2) JAK1 inhibitor brepocitinib, and the TYK2 inhibitor PF-06826647.

“This technique has been used in oncology,” Dr. Kimball said, noting that the ability to test multiple drugs at the same time “means we can really much more efficiently test two different things at the same time, and also put fewer patients at risk for potential problems if drugs don’t work.”
 

Positive signs for brepocitinib, not the other kinases tested

The results showed that though brepocitinib worked in HS, the other two novel compounds did not appear to have beneficial effects. Just over half (52%) of the 52 patients treated with brepocitinib achieved an HiSCR at 16 weeks, compared with around one-third of those given placebo, PF-06650833, or PF-06826647.

A similar benefit was seen in terms of reduction in flares for brepocitinib but not the other agents, although there was no difference between them all in terms of NPRS30 pain reduction.

“We’ve been able to test three different modalities. This tells us some things about the pathophysiology for HS, which is a very profoundly intensive inflammatory process,” which, Dr. Kimball said, “may require multiple modalities of action to get it under control.” In addition, these “general modalities seem to safe and well tolerated,” she added.
 

Take-homes for practice and future research

“While it is disappointing that two of the drugs tested did not clearly demonstrate efficacy, it is very possible that these mechanisms of action may be successful targets in the future as new dosing strategies and drugs targeting these pathways are developed,” Dr. Sayed said.

A case in point, he added, was that “adalimumab did not meet treatment endpoints at a dose of 40 mg every other week, but clearly has made a major impact at 40 mg weekly.”

The bottom line is that “both secukinumab and beprocitinib demonstrated efficacy over placebo and are likely to be helpful for a significant number of patients with HS,” Dr. Sayed said. “Hopefully, we’ll see head-to-head trials and more data regarding proportions of patients with deeper responses using criteria such as HiSCR75 and HiSCR90.”

Moreover, “having a larger number of drugs with a range of mechanisms of action is extraordinarily helpful given how difficult the disease can be to manage. We will hopefully continue to see creative approaches and further successes in the current wave of phase 1, 2, and 3 trials that are already underway.”

The SUNSHINE and SUNRISE studies were funded by Novartis Pharma AG, Basel, Switzerland. The phase 2A study Dr. Kimball presented was sponsored by Pfizer.

Dr. Kimball disclosed ties to both Novartis and Pfizer and acts as a consultant and investigator to AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, and UCB. She is an investigator for Incyte and AnaptysBio; acts as a consultant to Bayer, Boehringer Ingelheim, Ventyz, Moonlake, Lily, Concert, EvoImmune, Sonoma Bio, and Sanofi; receives fellowship funding from Janssen, and serves on the Board of Directors for Almirall.

Dr. Patel had no conflicts of interest to disclose. Dr. Sayed is the director of the HS Foundation, a nonprofit organization, and has acted as an adviser or consultant to, speaker for, and received research funding from multiple drug companies including AbbVie, ChemoCentryx, Incyte, InflaRx, Novartis, and UCB.

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