Key clinical point: Nanoparticle albumin-bound (nab) paclitaxel showed a superior pathological complete response (pCR) rate but similar disease-free survival (DFS) compared with docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC).

Major finding: Rate of pCR was significantly higher in the nab-paclitaxel vs. docetaxel group (36.71% vs. 20.00%; P = .031); however, DFS was not significantly different (P = .331). At least 1 drug-related adverse event was reported in 94.94% vs. 95.00% patients in the nab-paclitaxel vs. docetaxel group.

Study details: Findings are from a retrospective analysis of 159 patients with HER2-negative invasive BC who underwent surgery after receiving nab-paclitaxel (n = 79) or docetaxel (n = 80), both with epirubicin and cyclophosphamide.

Disclosures: This study was funded by the Postdoctoral Science Foundation of China, Natural Science Foundation of Shandong Province, and others. The authors declared no conflicts of interest.

Source: Lv Z-D et al. Front Oncol. 2022 (Jan 11). Doi: 10.3389/fonc.2021.760655.

Key clinical point: Nanoparticle albumin-bound (nab) paclitaxel showed a superior pathological complete response (pCR) rate but similar disease-free survival (DFS) compared with docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC).

Major finding: Rate of pCR was significantly higher in the nab-paclitaxel vs. docetaxel group (36.71% vs. 20.00%; P = .031); however, DFS was not significantly different (P = .331). At least 1 drug-related adverse event was reported in 94.94% vs. 95.00% patients in the nab-paclitaxel vs. docetaxel group.

Study details: Findings are from a retrospective analysis of 159 patients with HER2-negative invasive BC who underwent surgery after receiving nab-paclitaxel (n = 79) or docetaxel (n = 80), both with epirubicin and cyclophosphamide.

Disclosures: This study was funded by the Postdoctoral Science Foundation of China, Natural Science Foundation of Shandong Province, and others. The authors declared no conflicts of interest.

Source: Lv Z-D et al. Front Oncol. 2022 (Jan 11). Doi: 10.3389/fonc.2021.760655.

Key clinical point: Nanoparticle albumin-bound (nab) paclitaxel showed a superior pathological complete response (pCR) rate but similar disease-free survival (DFS) compared with docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC).

Major finding: Rate of pCR was significantly higher in the nab-paclitaxel vs. docetaxel group (36.71% vs. 20.00%; P = .031); however, DFS was not significantly different (P = .331). At least 1 drug-related adverse event was reported in 94.94% vs. 95.00% patients in the nab-paclitaxel vs. docetaxel group.

Study details: Findings are from a retrospective analysis of 159 patients with HER2-negative invasive BC who underwent surgery after receiving nab-paclitaxel (n = 79) or docetaxel (n = 80), both with epirubicin and cyclophosphamide.

Disclosures: This study was funded by the Postdoctoral Science Foundation of China, Natural Science Foundation of Shandong Province, and others. The authors declared no conflicts of interest.

Source: Lv Z-D et al. Front Oncol. 2022 (Jan 11). Doi: 10.3389/fonc.2021.760655.

Key clinical point: Human epidermal growth factor receptor 2 (HER2)-low expression was significantly discordant between early and advanced stages of invasive breast cancer (BC), with the expression being enriched in the advanced stages.

Major finding: Significant discordance in HER2 expression between the primary tumor and matched biopsy samples was observed in the overall population (Cohen’s kappa coefficient (K) 0.33; 95% CI 0.21-0.44) and in subgroups of estrogen receptor-positive (ER+) BC (K 0.32; 95% CI 0.19-0.45) and triple-negative (TN) BC (K 0.18; 95% CI −0.09 to 0.46) with HER2-low expression being enriched in advanced-stage biopsies vs. primary tumors in the overall population (64% vs. 53%), ER+ BC (71% vs. 57%), and TNBC (38% vs. 36%).

Study details: Findings are from a retrospective analysis of 232 patients with HER2-negative invasive BC.

Disclosures: This study was partially funded by the Italian Ministry of Health with Ricerca Corrente. Some of the authors declared serving as an advisor and consultant or receiving honoraria from several sources.

Source: Tarantino P et al. Eur J Cancer. 2022;163:P35-43 (Jan 13). Doi: 10.1016/j.ejca.2021.12.022.

Key clinical point: Human epidermal growth factor receptor 2 (HER2)-low expression was significantly discordant between early and advanced stages of invasive breast cancer (BC), with the expression being enriched in the advanced stages.

Major finding: Significant discordance in HER2 expression between the primary tumor and matched biopsy samples was observed in the overall population (Cohen’s kappa coefficient (K) 0.33; 95% CI 0.21-0.44) and in subgroups of estrogen receptor-positive (ER+) BC (K 0.32; 95% CI 0.19-0.45) and triple-negative (TN) BC (K 0.18; 95% CI −0.09 to 0.46) with HER2-low expression being enriched in advanced-stage biopsies vs. primary tumors in the overall population (64% vs. 53%), ER+ BC (71% vs. 57%), and TNBC (38% vs. 36%).

Study details: Findings are from a retrospective analysis of 232 patients with HER2-negative invasive BC.

Disclosures: This study was partially funded by the Italian Ministry of Health with Ricerca Corrente. Some of the authors declared serving as an advisor and consultant or receiving honoraria from several sources.

Source: Tarantino P et al. Eur J Cancer. 2022;163:P35-43 (Jan 13). Doi: 10.1016/j.ejca.2021.12.022.

Key clinical point: Human epidermal growth factor receptor 2 (HER2)-low expression was significantly discordant between early and advanced stages of invasive breast cancer (BC), with the expression being enriched in the advanced stages.

Major finding: Significant discordance in HER2 expression between the primary tumor and matched biopsy samples was observed in the overall population (Cohen’s kappa coefficient (K) 0.33; 95% CI 0.21-0.44) and in subgroups of estrogen receptor-positive (ER+) BC (K 0.32; 95% CI 0.19-0.45) and triple-negative (TN) BC (K 0.18; 95% CI −0.09 to 0.46) with HER2-low expression being enriched in advanced-stage biopsies vs. primary tumors in the overall population (64% vs. 53%), ER+ BC (71% vs. 57%), and TNBC (38% vs. 36%).

Study details: Findings are from a retrospective analysis of 232 patients with HER2-negative invasive BC.

Disclosures: This study was partially funded by the Italian Ministry of Health with Ricerca Corrente. Some of the authors declared serving as an advisor and consultant or receiving honoraria from several sources.

Source: Tarantino P et al. Eur J Cancer. 2022;163:P35-43 (Jan 13). Doi: 10.1016/j.ejca.2021.12.022.

Key clinical point: A regimen consisting of docetaxel and capecitabine (TX) followed by cyclophosphamide, epirubicin, and capecitabine (CEX) prolonged survival in patients with early breast cancer (BC) vs. a regimen containing of only docetaxel followed by cyclophosphamide, epirubicin, and fluorouracil (T-CEF).

Major finding: Patients assigned to TX-CEX vs. T-CEF arms had significantly higher 15-year survival rate (77.6% vs. 73.3%; hazard ratio [HR] 0.81; log-rank P = .037) with patients in the triple-negative subgroup benefitting the most (HR 0.59; 95% CI 0.36-0.97).

Study details: Findings are from the open-label, phase 3 FinXX study including 1,495 patients with axillary node-positive or high-risk node-negative early BC, who were randomly assigned to the TX-CEX or T-CEF arms.

Disclosures: This study was supported by Roche, Sanofi, AstraZeneca, the Cancer Society of Finland, and others. The authors declared serving as consultants, advisors, or on the speaker’s bureau or receiving honoraria and research funding from several sources.

Source: Joensuu H et al. J Clin Oncol. 2022 (Jan 12). Doi: 10.1200/JCO.21.02054.

Key clinical point: A regimen consisting of docetaxel and capecitabine (TX) followed by cyclophosphamide, epirubicin, and capecitabine (CEX) prolonged survival in patients with early breast cancer (BC) vs. a regimen containing of only docetaxel followed by cyclophosphamide, epirubicin, and fluorouracil (T-CEF).

Major finding: Patients assigned to TX-CEX vs. T-CEF arms had significantly higher 15-year survival rate (77.6% vs. 73.3%; hazard ratio [HR] 0.81; log-rank P = .037) with patients in the triple-negative subgroup benefitting the most (HR 0.59; 95% CI 0.36-0.97).

Study details: Findings are from the open-label, phase 3 FinXX study including 1,495 patients with axillary node-positive or high-risk node-negative early BC, who were randomly assigned to the TX-CEX or T-CEF arms.

Disclosures: This study was supported by Roche, Sanofi, AstraZeneca, the Cancer Society of Finland, and others. The authors declared serving as consultants, advisors, or on the speaker’s bureau or receiving honoraria and research funding from several sources.

Source: Joensuu H et al. J Clin Oncol. 2022 (Jan 12). Doi: 10.1200/JCO.21.02054.

Key clinical point: A regimen consisting of docetaxel and capecitabine (TX) followed by cyclophosphamide, epirubicin, and capecitabine (CEX) prolonged survival in patients with early breast cancer (BC) vs. a regimen containing of only docetaxel followed by cyclophosphamide, epirubicin, and fluorouracil (T-CEF).

Major finding: Patients assigned to TX-CEX vs. T-CEF arms had significantly higher 15-year survival rate (77.6% vs. 73.3%; hazard ratio [HR] 0.81; log-rank P = .037) with patients in the triple-negative subgroup benefitting the most (HR 0.59; 95% CI 0.36-0.97).

Study details: Findings are from the open-label, phase 3 FinXX study including 1,495 patients with axillary node-positive or high-risk node-negative early BC, who were randomly assigned to the TX-CEX or T-CEF arms.

Disclosures: This study was supported by Roche, Sanofi, AstraZeneca, the Cancer Society of Finland, and others. The authors declared serving as consultants, advisors, or on the speaker’s bureau or receiving honoraria and research funding from several sources.

Source: Joensuu H et al. J Clin Oncol. 2022 (Jan 12). Doi: 10.1200/JCO.21.02054.

Key clinical point: Fosnetupitant showed a favorable safety profile with a low risk of causing injection-site reactions in patients with breast cancer receiving chemotherapy with doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide (AC/EC).

Major finding: Treatment-related adverse events (TRAE) were reported by 21.2% vs. 22.0% of patients in fosnetupitant vs. fosaprepitant group with adverse events relevant to injection site reactions observed in 5.8% vs. 26.0% of patients in fosnetupitant vs. fosaprepitant groups. Grade 3 or higher TRAEs occurred in 9.6% vs. 0% patients in fosnetupitant vs. fosaprepitant groups, with none leading to death or treatment discontinuation.

Study details: Findings are from a phase 3 study including 102 patients with breast cancer receiving AC/EC chemotherapy who were randomly assigned to receive fosnetupitant or fosaprepitant, both in combination with intravenous palonosetron and dexamethasone.

Disclosures: This study was funded by Taiho Pharmaceutical Co, Ltd. The authors declared receiving grants, consulting fees, payments, honoraria, travel support, or contracts from several sources including Taiho Pharmaceutical Co, Ltd.

Source: Matsuura K et al. Cancer. 2022 (Jan 19). Doi: 10.1002/cncr.34088.

Key clinical point: Fosnetupitant showed a favorable safety profile with a low risk of causing injection-site reactions in patients with breast cancer receiving chemotherapy with doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide (AC/EC).

Major finding: Treatment-related adverse events (TRAE) were reported by 21.2% vs. 22.0% of patients in fosnetupitant vs. fosaprepitant group with adverse events relevant to injection site reactions observed in 5.8% vs. 26.0% of patients in fosnetupitant vs. fosaprepitant groups. Grade 3 or higher TRAEs occurred in 9.6% vs. 0% patients in fosnetupitant vs. fosaprepitant groups, with none leading to death or treatment discontinuation.

Study details: Findings are from a phase 3 study including 102 patients with breast cancer receiving AC/EC chemotherapy who were randomly assigned to receive fosnetupitant or fosaprepitant, both in combination with intravenous palonosetron and dexamethasone.

Disclosures: This study was funded by Taiho Pharmaceutical Co, Ltd. The authors declared receiving grants, consulting fees, payments, honoraria, travel support, or contracts from several sources including Taiho Pharmaceutical Co, Ltd.

Source: Matsuura K et al. Cancer. 2022 (Jan 19). Doi: 10.1002/cncr.34088.

Key clinical point: Fosnetupitant showed a favorable safety profile with a low risk of causing injection-site reactions in patients with breast cancer receiving chemotherapy with doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide (AC/EC).

Major finding: Treatment-related adverse events (TRAE) were reported by 21.2% vs. 22.0% of patients in fosnetupitant vs. fosaprepitant group with adverse events relevant to injection site reactions observed in 5.8% vs. 26.0% of patients in fosnetupitant vs. fosaprepitant groups. Grade 3 or higher TRAEs occurred in 9.6% vs. 0% patients in fosnetupitant vs. fosaprepitant groups, with none leading to death or treatment discontinuation.

Study details: Findings are from a phase 3 study including 102 patients with breast cancer receiving AC/EC chemotherapy who were randomly assigned to receive fosnetupitant or fosaprepitant, both in combination with intravenous palonosetron and dexamethasone.

Disclosures: This study was funded by Taiho Pharmaceutical Co, Ltd. The authors declared receiving grants, consulting fees, payments, honoraria, travel support, or contracts from several sources including Taiho Pharmaceutical Co, Ltd.

Source: Matsuura K et al. Cancer. 2022 (Jan 19). Doi: 10.1002/cncr.34088.

Key clinical point: Aromatase inhibitor vs. tamoxifen reduced the risk for breast cancer (BC) recurrence in premenopausal women with early-stage, estrogen receptor-positive (ER+) BC receiving ovarian suppression.

Major finding: Aromatase inhibitor vs. tamoxifen was associated with significantly reduced rates of BC recurrence during the first 4 years of follow-up (risk ratio [RR] 0.68; P < .0001) and distant recurrence (RR 0.83; P = .018). No significant differences in breast cancer mortality, death without recurrence, or all-cause mortality were observed between the treatment groups.

Study details: Findings are a meta-analysis of 4 phase 3 trials (ABCSG-XII, TEXT, SOFT, and HOBOE) including 7,030 premenopausal women with ER+ BC who were randomly assigned to aromatase inhibitors (anastrozole, exemestane, or letrozole) or tamoxifen for 3 or 5 years, all in combination with ovarian suppression or ablation.

Disclosures: This study was funded by the Cancer Research UK and UK Medical Research Council. The authors declared serving as leaders and fiduciaries or receiving grants, consulting fees, travel support, or honoraria from several sources.

Source: Early Breast Cancer Trialists' Collaborative Group. Lancet Oncol. 2022 (Feb 3). Doi: 10.1016/S1470-2045(21)00758-0.

Key clinical point: Aromatase inhibitor vs. tamoxifen reduced the risk for breast cancer (BC) recurrence in premenopausal women with early-stage, estrogen receptor-positive (ER+) BC receiving ovarian suppression.

Major finding: Aromatase inhibitor vs. tamoxifen was associated with significantly reduced rates of BC recurrence during the first 4 years of follow-up (risk ratio [RR] 0.68; P < .0001) and distant recurrence (RR 0.83; P = .018). No significant differences in breast cancer mortality, death without recurrence, or all-cause mortality were observed between the treatment groups.

Study details: Findings are a meta-analysis of 4 phase 3 trials (ABCSG-XII, TEXT, SOFT, and HOBOE) including 7,030 premenopausal women with ER+ BC who were randomly assigned to aromatase inhibitors (anastrozole, exemestane, or letrozole) or tamoxifen for 3 or 5 years, all in combination with ovarian suppression or ablation.

Disclosures: This study was funded by the Cancer Research UK and UK Medical Research Council. The authors declared serving as leaders and fiduciaries or receiving grants, consulting fees, travel support, or honoraria from several sources.

Source: Early Breast Cancer Trialists' Collaborative Group. Lancet Oncol. 2022 (Feb 3). Doi: 10.1016/S1470-2045(21)00758-0.

Key clinical point: Aromatase inhibitor vs. tamoxifen reduced the risk for breast cancer (BC) recurrence in premenopausal women with early-stage, estrogen receptor-positive (ER+) BC receiving ovarian suppression.

Major finding: Aromatase inhibitor vs. tamoxifen was associated with significantly reduced rates of BC recurrence during the first 4 years of follow-up (risk ratio [RR] 0.68; P < .0001) and distant recurrence (RR 0.83; P = .018). No significant differences in breast cancer mortality, death without recurrence, or all-cause mortality were observed between the treatment groups.

Study details: Findings are a meta-analysis of 4 phase 3 trials (ABCSG-XII, TEXT, SOFT, and HOBOE) including 7,030 premenopausal women with ER+ BC who were randomly assigned to aromatase inhibitors (anastrozole, exemestane, or letrozole) or tamoxifen for 3 or 5 years, all in combination with ovarian suppression or ablation.

Disclosures: This study was funded by the Cancer Research UK and UK Medical Research Council. The authors declared serving as leaders and fiduciaries or receiving grants, consulting fees, travel support, or honoraria from several sources.

Source: Early Breast Cancer Trialists' Collaborative Group. Lancet Oncol. 2022 (Feb 3). Doi: 10.1016/S1470-2045(21)00758-0.

Key clinical point: Protein-truncating variants (PTV) of 9 breast cancer (BC) risk genes showed substantial differences in tumor pathology and were generally associated with triple-negative (TN) or high-grade disease.

Major finding: BRCA1 showed the highest association for TN disease (odds ratio [OR] 55.32; 95% CI 40.51-75.55) and ATM variants for the hormone receptor-positive (HR+) erb-b2 receptor tyrosine kinase 2-negative (ERBB2−) high-grade subtype (OR 4.99; 95% CI 3.68-6.76). RAD51C (OR 6.19; 95% CI 3.17-12.12), RAD51D (OR 6.19; 95% CI 2.99-12.79), and BARD1 (OR 10.05; 95% CI 5.27-19.19) were most strongly associated with TN disease. PALB2 PTVs showed higher ORs for HR+ERBB2− high-grade subtype (OR 9.43; 95% CI 6.24- 14.25) and TN disease (OR 8.05; 95% CI 5.17-12.53).

Study details: This was a case-control analysis of the BRIDGES study including 42,680 patients with BC who were matched with 46,387 healthy controls.

Disclosures: This study was funded by the European Union Horizon 2020 research and innovation program, Wellcome Trust, and several other sources. The authors declared receiving grants, honorariums, personal fees, or awards from several sources.

Source: Breast Cancer Association Consortium. JAMA Oncol. 2022 (Jan 27). Doi: 10.1001/jamaoncol.2021.6744.

Key clinical point: Protein-truncating variants (PTV) of 9 breast cancer (BC) risk genes showed substantial differences in tumor pathology and were generally associated with triple-negative (TN) or high-grade disease.

Major finding: BRCA1 showed the highest association for TN disease (odds ratio [OR] 55.32; 95% CI 40.51-75.55) and ATM variants for the hormone receptor-positive (HR+) erb-b2 receptor tyrosine kinase 2-negative (ERBB2−) high-grade subtype (OR 4.99; 95% CI 3.68-6.76). RAD51C (OR 6.19; 95% CI 3.17-12.12), RAD51D (OR 6.19; 95% CI 2.99-12.79), and BARD1 (OR 10.05; 95% CI 5.27-19.19) were most strongly associated with TN disease. PALB2 PTVs showed higher ORs for HR+ERBB2− high-grade subtype (OR 9.43; 95% CI 6.24- 14.25) and TN disease (OR 8.05; 95% CI 5.17-12.53).

Study details: This was a case-control analysis of the BRIDGES study including 42,680 patients with BC who were matched with 46,387 healthy controls.

Disclosures: This study was funded by the European Union Horizon 2020 research and innovation program, Wellcome Trust, and several other sources. The authors declared receiving grants, honorariums, personal fees, or awards from several sources.

Source: Breast Cancer Association Consortium. JAMA Oncol. 2022 (Jan 27). Doi: 10.1001/jamaoncol.2021.6744.

Key clinical point: Protein-truncating variants (PTV) of 9 breast cancer (BC) risk genes showed substantial differences in tumor pathology and were generally associated with triple-negative (TN) or high-grade disease.

Major finding: BRCA1 showed the highest association for TN disease (odds ratio [OR] 55.32; 95% CI 40.51-75.55) and ATM variants for the hormone receptor-positive (HR+) erb-b2 receptor tyrosine kinase 2-negative (ERBB2−) high-grade subtype (OR 4.99; 95% CI 3.68-6.76). RAD51C (OR 6.19; 95% CI 3.17-12.12), RAD51D (OR 6.19; 95% CI 2.99-12.79), and BARD1 (OR 10.05; 95% CI 5.27-19.19) were most strongly associated with TN disease. PALB2 PTVs showed higher ORs for HR+ERBB2− high-grade subtype (OR 9.43; 95% CI 6.24- 14.25) and TN disease (OR 8.05; 95% CI 5.17-12.53).

Study details: This was a case-control analysis of the BRIDGES study including 42,680 patients with BC who were matched with 46,387 healthy controls.

Disclosures: This study was funded by the European Union Horizon 2020 research and innovation program, Wellcome Trust, and several other sources. The authors declared receiving grants, honorariums, personal fees, or awards from several sources.

Source: Breast Cancer Association Consortium. JAMA Oncol. 2022 (Jan 27). Doi: 10.1001/jamaoncol.2021.6744.

Key clinical point: A regimen consisting of docetaxel and capecitabine (TX) followed by cyclophosphamide, epirubicin, and capecitabine (CEX) vs. only docetaxel followed by cyclophosphamide, epirubicin, and fluorouracil (T-CEF) prolonged recurrence-free survival (RFS) in patients with non- BRCA1-like early triple-negative breast cancer (TNBC).

Major finding: Overall, patients assigned to TX-CEX vs. T-CEF arms had higher RFS (hazard ratio [HR] 0.39; P = .01), with the capecitabine-containing chemotherapy being significantly more effective than conventional chemotherapy in patients with non-BRCA1-like tumor (HR 0.23; P < .01) but not in patients with BRCA1-like tumor (HR 0.66; P = .42).

Study details: Findings are from the open-label, phase 3 FinXX study including 202 patients with early TNBC who were randomly assigned to TX-CEX or T-CEF arms.  BRCA1-like status was obtained for 129 patients.

Disclosures: This work was supported by the Dutch Cancer Society. The authors declared serving as board members and employees or receiving fees, grants, nonfinancial, and research support from several sources.

Source: de Boo LW et al. Br J Cancer. 2022 (Feb 5). Doi: 10.1038/s41416-022-01711-y.

Key clinical point: A regimen consisting of docetaxel and capecitabine (TX) followed by cyclophosphamide, epirubicin, and capecitabine (CEX) vs. only docetaxel followed by cyclophosphamide, epirubicin, and fluorouracil (T-CEF) prolonged recurrence-free survival (RFS) in patients with non- BRCA1-like early triple-negative breast cancer (TNBC).

Major finding: Overall, patients assigned to TX-CEX vs. T-CEF arms had higher RFS (hazard ratio [HR] 0.39; P = .01), with the capecitabine-containing chemotherapy being significantly more effective than conventional chemotherapy in patients with non-BRCA1-like tumor (HR 0.23; P < .01) but not in patients with BRCA1-like tumor (HR 0.66; P = .42).

Study details: Findings are from the open-label, phase 3 FinXX study including 202 patients with early TNBC who were randomly assigned to TX-CEX or T-CEF arms.  BRCA1-like status was obtained for 129 patients.

Disclosures: This work was supported by the Dutch Cancer Society. The authors declared serving as board members and employees or receiving fees, grants, nonfinancial, and research support from several sources.

Source: de Boo LW et al. Br J Cancer. 2022 (Feb 5). Doi: 10.1038/s41416-022-01711-y.

Key clinical point: A regimen consisting of docetaxel and capecitabine (TX) followed by cyclophosphamide, epirubicin, and capecitabine (CEX) vs. only docetaxel followed by cyclophosphamide, epirubicin, and fluorouracil (T-CEF) prolonged recurrence-free survival (RFS) in patients with non- BRCA1-like early triple-negative breast cancer (TNBC).

Major finding: Overall, patients assigned to TX-CEX vs. T-CEF arms had higher RFS (hazard ratio [HR] 0.39; P = .01), with the capecitabine-containing chemotherapy being significantly more effective than conventional chemotherapy in patients with non-BRCA1-like tumor (HR 0.23; P < .01) but not in patients with BRCA1-like tumor (HR 0.66; P = .42).

Study details: Findings are from the open-label, phase 3 FinXX study including 202 patients with early TNBC who were randomly assigned to TX-CEX or T-CEF arms.  BRCA1-like status was obtained for 129 patients.

Disclosures: This work was supported by the Dutch Cancer Society. The authors declared serving as board members and employees or receiving fees, grants, nonfinancial, and research support from several sources.

Source: de Boo LW et al. Br J Cancer. 2022 (Feb 5). Doi: 10.1038/s41416-022-01711-y.

Key clinical point: Adding carboplatin to neoadjuvant paclitaxel followed by doxorubicin and cyclophosphamide improved long-term event-free survival (EFS) along with a manageable safety profile in patients with triple-negative breast cancer (TNBC).

Major finding: Patients receiving carboplatin+veliparib+paclitaxel vs. paclitaxel showed significant improvements in EFS (hazard ratio [HR] 0.63; P = .02), whereas EFS was not significntly different among patients assigned to carboplatin+veliparib+paclitaxel vs. carboplatin+paclitaxel (HR 1.12; P = .62). Rates of treatment-emergent and post-treatment-emergent adverse events and secondary malignancies were similar across treatment groups.

Study details: Findings are based on the 4.5-year follow-up data from the phase 3 BrighTNess trial including 634 patients with stage II-III TNBC who were randomly assigned to receive carboplatin+veliparib, carboplatin+veliparib placebo, or carboplatin placebo+veliparib placebo, all in combination with paclitaxel.

Disclosures: This study was supported by AbbVie. Some authors declared serving on the advisory board and speaker’s bureau or receiving travel funds, writing support, honoraria, research funds, and consulting fees from several sources including AbbVie. D Maag declared being an employee or stockholder of AbbVie.

Source: Geyer CE Jr et al. Ann Oncol. 2022 (Jan 27). Doi: 10.1016/j.annonc.2022.01.009.

Key clinical point: Adding carboplatin to neoadjuvant paclitaxel followed by doxorubicin and cyclophosphamide improved long-term event-free survival (EFS) along with a manageable safety profile in patients with triple-negative breast cancer (TNBC).

Major finding: Patients receiving carboplatin+veliparib+paclitaxel vs. paclitaxel showed significant improvements in EFS (hazard ratio [HR] 0.63; P = .02), whereas EFS was not significntly different among patients assigned to carboplatin+veliparib+paclitaxel vs. carboplatin+paclitaxel (HR 1.12; P = .62). Rates of treatment-emergent and post-treatment-emergent adverse events and secondary malignancies were similar across treatment groups.

Study details: Findings are based on the 4.5-year follow-up data from the phase 3 BrighTNess trial including 634 patients with stage II-III TNBC who were randomly assigned to receive carboplatin+veliparib, carboplatin+veliparib placebo, or carboplatin placebo+veliparib placebo, all in combination with paclitaxel.

Disclosures: This study was supported by AbbVie. Some authors declared serving on the advisory board and speaker’s bureau or receiving travel funds, writing support, honoraria, research funds, and consulting fees from several sources including AbbVie. D Maag declared being an employee or stockholder of AbbVie.

Source: Geyer CE Jr et al. Ann Oncol. 2022 (Jan 27). Doi: 10.1016/j.annonc.2022.01.009.

Key clinical point: Adding carboplatin to neoadjuvant paclitaxel followed by doxorubicin and cyclophosphamide improved long-term event-free survival (EFS) along with a manageable safety profile in patients with triple-negative breast cancer (TNBC).

Major finding: Patients receiving carboplatin+veliparib+paclitaxel vs. paclitaxel showed significant improvements in EFS (hazard ratio [HR] 0.63; P = .02), whereas EFS was not significntly different among patients assigned to carboplatin+veliparib+paclitaxel vs. carboplatin+paclitaxel (HR 1.12; P = .62). Rates of treatment-emergent and post-treatment-emergent adverse events and secondary malignancies were similar across treatment groups.

Study details: Findings are based on the 4.5-year follow-up data from the phase 3 BrighTNess trial including 634 patients with stage II-III TNBC who were randomly assigned to receive carboplatin+veliparib, carboplatin+veliparib placebo, or carboplatin placebo+veliparib placebo, all in combination with paclitaxel.

Disclosures: This study was supported by AbbVie. Some authors declared serving on the advisory board and speaker’s bureau or receiving travel funds, writing support, honoraria, research funds, and consulting fees from several sources including AbbVie. D Maag declared being an employee or stockholder of AbbVie.

Source: Geyer CE Jr et al. Ann Oncol. 2022 (Jan 27). Doi: 10.1016/j.annonc.2022.01.009.

Key clinical point: Pyrotinib+capecitabine showed intracranial objective response and was well tolerated in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC) and brain metastases in the PERMEATE phase 2 study.

Major finding: The intracranial objective response rate was 74.6% (95% CI 61.6%-85.0%) in radiotherapy-naive patients and 42.1% (95% CI 20.3%-66.5%) in patients with progressive disease after whole-brain radiotherapy. Common grade 3 treatment-emergent adverse events were diarrhea and decreased white blood cell count. No treatment-related deaths were reported.

Study details: Findings are from the single-arm, phase 2 PERMEATE study including 78 patients with HER2+ BC and brain metastases who were either radiotherapy-naive or had progressive disease after radiotherapy. Patients received 400 mg pyrotinib once daily and 1000 mg/m² capecitabine twice daily for 14 days, followed by 7 days off during each 21-day cycle.

Disclosures: This study was funded by the National Cancer Centre Climbing Foundation Key Project of China and Jiangsu Hengrui Pharmaceuticals. The authors declared no conflicts of interest.

Source: Yan M et al. Lancet Oncol. 2022 (Jan 24). Doi: 10.1016/S1470-2045(21)00716-6.

Key clinical point: Pyrotinib+capecitabine showed intracranial objective response and was well tolerated in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC) and brain metastases in the PERMEATE phase 2 study.

Major finding: The intracranial objective response rate was 74.6% (95% CI 61.6%-85.0%) in radiotherapy-naive patients and 42.1% (95% CI 20.3%-66.5%) in patients with progressive disease after whole-brain radiotherapy. Common grade 3 treatment-emergent adverse events were diarrhea and decreased white blood cell count. No treatment-related deaths were reported.

Study details: Findings are from the single-arm, phase 2 PERMEATE study including 78 patients with HER2+ BC and brain metastases who were either radiotherapy-naive or had progressive disease after radiotherapy. Patients received 400 mg pyrotinib once daily and 1000 mg/m² capecitabine twice daily for 14 days, followed by 7 days off during each 21-day cycle.

Disclosures: This study was funded by the National Cancer Centre Climbing Foundation Key Project of China and Jiangsu Hengrui Pharmaceuticals. The authors declared no conflicts of interest.

Source: Yan M et al. Lancet Oncol. 2022 (Jan 24). Doi: 10.1016/S1470-2045(21)00716-6.

Key clinical point: Pyrotinib+capecitabine showed intracranial objective response and was well tolerated in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC) and brain metastases in the PERMEATE phase 2 study.

Major finding: The intracranial objective response rate was 74.6% (95% CI 61.6%-85.0%) in radiotherapy-naive patients and 42.1% (95% CI 20.3%-66.5%) in patients with progressive disease after whole-brain radiotherapy. Common grade 3 treatment-emergent adverse events were diarrhea and decreased white blood cell count. No treatment-related deaths were reported.

Study details: Findings are from the single-arm, phase 2 PERMEATE study including 78 patients with HER2+ BC and brain metastases who were either radiotherapy-naive or had progressive disease after radiotherapy. Patients received 400 mg pyrotinib once daily and 1000 mg/m² capecitabine twice daily for 14 days, followed by 7 days off during each 21-day cycle.

Disclosures: This study was funded by the National Cancer Centre Climbing Foundation Key Project of China and Jiangsu Hengrui Pharmaceuticals. The authors declared no conflicts of interest.

Source: Yan M et al. Lancet Oncol. 2022 (Jan 24). Doi: 10.1016/S1470-2045(21)00716-6.

Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.

Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.

However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
 

Update needed in wake of Omicron

“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.

“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.

“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.

“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”

Diagnostic evaluation

The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.

Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
 

MIS-C and Kawasaki disease phenotypes

Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.

Cardiac management

Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms. 

MIS-C treatment

Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.

When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.

The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
 

COVID-19 and hyperinflammation

The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”

The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.

Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”

The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.

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

Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.

Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.

However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
 

Update needed in wake of Omicron

“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.

“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.

“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.

“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”

Diagnostic evaluation

The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.

Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
 

MIS-C and Kawasaki disease phenotypes

Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.

Cardiac management

Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms. 

MIS-C treatment

Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.

When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.

The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
 

COVID-19 and hyperinflammation

The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”

The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.

Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”

The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.

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

Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.

Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.

However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
 

Update needed in wake of Omicron

“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.

“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.

“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.

“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”

Diagnostic evaluation

The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.

Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
 

MIS-C and Kawasaki disease phenotypes

Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.

Cardiac management

Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms. 

MIS-C treatment

Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.

When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.

The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
 

COVID-19 and hyperinflammation

The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”

The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.

Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”

The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.

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