Clinical Edge Journal Scan

Key clinical point: Brexucabtagene autoleucel (brexu-cel) provides survival benefit over non-chimeric antigen receptor (CAR) T-cell standard of care (SOC) in patients with relapsed or refractory mantle cell lymphoma (MCL) treated with covalent Bruton tyrosine kinase inhibitors (BTKi).

Major finding: Inverse probability weighting showed that brexu-cel vs SOC led to a significantly reduced risk for death (adjusted hazard ratio 0.38; P < .001), with the findings being similar for other adjusted comparisons.

Study details: This indirect comparison study analyzed the individual patient data of BTKi-treated patients with relapsed or refractory MCL who received brexu-cel in ZUMA-2 (n = 68) and non-CAR T-cell SOC in SCHOLAR-2 (n = 149).

Disclosures: This study was sponsored by Kite, a Gilead Company. Some authors declared participating in the data safety monitoring or advisory boards of or receiving grants, consulting fees, travel support, or honoraria for lectures, etc., from Kite, Gilead, and others. Five authors declared being employees or stockowners of Kite, Gilead, or PRECISIONheor.

Source: Hess G et al. Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Leuk Lymphoma. 2023 (Oct 16). doi: 10.1080/10428194.2023.2268228

Key clinical point: Brexucabtagene autoleucel (brexu-cel) provides survival benefit over non-chimeric antigen receptor (CAR) T-cell standard of care (SOC) in patients with relapsed or refractory mantle cell lymphoma (MCL) treated with covalent Bruton tyrosine kinase inhibitors (BTKi).

Major finding: Inverse probability weighting showed that brexu-cel vs SOC led to a significantly reduced risk for death (adjusted hazard ratio 0.38; P < .001), with the findings being similar for other adjusted comparisons.

Study details: This indirect comparison study analyzed the individual patient data of BTKi-treated patients with relapsed or refractory MCL who received brexu-cel in ZUMA-2 (n = 68) and non-CAR T-cell SOC in SCHOLAR-2 (n = 149).

Disclosures: This study was sponsored by Kite, a Gilead Company. Some authors declared participating in the data safety monitoring or advisory boards of or receiving grants, consulting fees, travel support, or honoraria for lectures, etc., from Kite, Gilead, and others. Five authors declared being employees or stockowners of Kite, Gilead, or PRECISIONheor.

Source: Hess G et al. Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Leuk Lymphoma. 2023 (Oct 16). doi: 10.1080/10428194.2023.2268228

Key clinical point: Brexucabtagene autoleucel (brexu-cel) provides survival benefit over non-chimeric antigen receptor (CAR) T-cell standard of care (SOC) in patients with relapsed or refractory mantle cell lymphoma (MCL) treated with covalent Bruton tyrosine kinase inhibitors (BTKi).

Major finding: Inverse probability weighting showed that brexu-cel vs SOC led to a significantly reduced risk for death (adjusted hazard ratio 0.38; P < .001), with the findings being similar for other adjusted comparisons.

Study details: This indirect comparison study analyzed the individual patient data of BTKi-treated patients with relapsed or refractory MCL who received brexu-cel in ZUMA-2 (n = 68) and non-CAR T-cell SOC in SCHOLAR-2 (n = 149).

Disclosures: This study was sponsored by Kite, a Gilead Company. Some authors declared participating in the data safety monitoring or advisory boards of or receiving grants, consulting fees, travel support, or honoraria for lectures, etc., from Kite, Gilead, and others. Five authors declared being employees or stockowners of Kite, Gilead, or PRECISIONheor.

Source: Hess G et al. Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Leuk Lymphoma. 2023 (Oct 16). doi: 10.1080/10428194.2023.2268228

Key clinical point: Patients with relapsed or refractory large B-cell lymphoma (LBCL) who were recently exposed to preapheresis bendamustine showed negative treatment outcomes, hematologic toxicity, and severe infections after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy.

Major finding: Patients recently exposed to bendamustine (<9 months) vs those naive to it before apheresis had a significantly lower overall response rate (40% vs 66%; P  =  .01) and shorter overall survival (adjusted hazard ratio [aHR] 2.11; P < .01) and progression-free survival (aHR 1.82; P < .01) after CAR T-cell infusion.

Study details: This retrospective multicenter study included 439 patients with relapsed or refractory LBCL who received CD19-targeted commercial CAR T-cell therapy after ≥2 prior treatment lines, of whom 80 patients had received bendamustine before apheresis.

Disclosures: This study was supported by the Carlos III Health Institute, Spain, and others. Some authors declared serving in consulting or advisory roles for or as members of speakers’ bureaus of or receiving honoraria, research funding, or travel or accommodation expenses from various sources.

Source: Iacoboni G et al. Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy. J Clin Oncol. 2023 (Oct 24). doi: 10.1200/JCO.23.01097

Key clinical point: Patients with relapsed or refractory large B-cell lymphoma (LBCL) who were recently exposed to preapheresis bendamustine showed negative treatment outcomes, hematologic toxicity, and severe infections after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy.

Major finding: Patients recently exposed to bendamustine (<9 months) vs those naive to it before apheresis had a significantly lower overall response rate (40% vs 66%; P  =  .01) and shorter overall survival (adjusted hazard ratio [aHR] 2.11; P < .01) and progression-free survival (aHR 1.82; P < .01) after CAR T-cell infusion.

Study details: This retrospective multicenter study included 439 patients with relapsed or refractory LBCL who received CD19-targeted commercial CAR T-cell therapy after ≥2 prior treatment lines, of whom 80 patients had received bendamustine before apheresis.

Disclosures: This study was supported by the Carlos III Health Institute, Spain, and others. Some authors declared serving in consulting or advisory roles for or as members of speakers’ bureaus of or receiving honoraria, research funding, or travel or accommodation expenses from various sources.

Source: Iacoboni G et al. Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy. J Clin Oncol. 2023 (Oct 24). doi: 10.1200/JCO.23.01097

Key clinical point: Patients with relapsed or refractory large B-cell lymphoma (LBCL) who were recently exposed to preapheresis bendamustine showed negative treatment outcomes, hematologic toxicity, and severe infections after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy.

Major finding: Patients recently exposed to bendamustine (<9 months) vs those naive to it before apheresis had a significantly lower overall response rate (40% vs 66%; P  =  .01) and shorter overall survival (adjusted hazard ratio [aHR] 2.11; P < .01) and progression-free survival (aHR 1.82; P < .01) after CAR T-cell infusion.

Study details: This retrospective multicenter study included 439 patients with relapsed or refractory LBCL who received CD19-targeted commercial CAR T-cell therapy after ≥2 prior treatment lines, of whom 80 patients had received bendamustine before apheresis.

Disclosures: This study was supported by the Carlos III Health Institute, Spain, and others. Some authors declared serving in consulting or advisory roles for or as members of speakers’ bureaus of or receiving honoraria, research funding, or travel or accommodation expenses from various sources.

Source: Iacoboni G et al. Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy. J Clin Oncol. 2023 (Oct 24). doi: 10.1200/JCO.23.01097

Key clinical point: In women with locally advanced breast cancer (LABC) who received neoadjuvant treatment (NAT) followed by breast surgery, the type of breast surgery, pathological complete response (pCR), body mass index (BMI), and pretreatment stage of tumors were the significant predictors of survival outcomes.

Major finding: Overall survival was significantly improved in patients with LABC who did vs did not achieve pCR (odds ratio [OR] 0.42; P = .008). However, it was much worsened in patients who underwent mastectomy vs breast-conserving surgery (BCS; OR 1.678; P = .024), had higher vs lower BMI (OR 1.031; P = .017), and had stage IIIB or IIIC vs IIB tumors (OR 2.450; P < .001).

Study details: Findings are from a retrospective cohort study including 530 patients with LABC, of which 24.6% of patients underwent BCS after receiving NAT.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nobrega GB et al. Locally advanced breast cancer: Breast-conserving surgery and other factors linked to overall survival after neoadjuvant treatment. Front Oncol. 2023;13:1293288 (Nov 6). doi: 10.3389/fonc.2023.1293288

Key clinical point: In women with locally advanced breast cancer (LABC) who received neoadjuvant treatment (NAT) followed by breast surgery, the type of breast surgery, pathological complete response (pCR), body mass index (BMI), and pretreatment stage of tumors were the significant predictors of survival outcomes.

Major finding: Overall survival was significantly improved in patients with LABC who did vs did not achieve pCR (odds ratio [OR] 0.42; P = .008). However, it was much worsened in patients who underwent mastectomy vs breast-conserving surgery (BCS; OR 1.678; P = .024), had higher vs lower BMI (OR 1.031; P = .017), and had stage IIIB or IIIC vs IIB tumors (OR 2.450; P < .001).

Study details: Findings are from a retrospective cohort study including 530 patients with LABC, of which 24.6% of patients underwent BCS after receiving NAT.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nobrega GB et al. Locally advanced breast cancer: Breast-conserving surgery and other factors linked to overall survival after neoadjuvant treatment. Front Oncol. 2023;13:1293288 (Nov 6). doi: 10.3389/fonc.2023.1293288

Key clinical point: In women with locally advanced breast cancer (LABC) who received neoadjuvant treatment (NAT) followed by breast surgery, the type of breast surgery, pathological complete response (pCR), body mass index (BMI), and pretreatment stage of tumors were the significant predictors of survival outcomes.

Major finding: Overall survival was significantly improved in patients with LABC who did vs did not achieve pCR (odds ratio [OR] 0.42; P = .008). However, it was much worsened in patients who underwent mastectomy vs breast-conserving surgery (BCS; OR 1.678; P = .024), had higher vs lower BMI (OR 1.031; P = .017), and had stage IIIB or IIIC vs IIB tumors (OR 2.450; P < .001).

Study details: Findings are from a retrospective cohort study including 530 patients with LABC, of which 24.6% of patients underwent BCS after receiving NAT.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nobrega GB et al. Locally advanced breast cancer: Breast-conserving surgery and other factors linked to overall survival after neoadjuvant treatment. Front Oncol. 2023;13:1293288 (Nov 6). doi: 10.3389/fonc.2023.1293288

Key clinical point: Patients with breast cancer (BC) who underwent post-mastectomy breast reconstruction followed by post-mastectomy radiotherapy (PMRT) had an increased risk for postoperative complications, such as infections and contractures, than those who did not receive PMRT.

Major finding: Patients who did vs did not receive PMRT had a significantly higher risk for postoperative wound infections (odds ratio [OR] 1.95; P = .003) and skin contractures (OR 7.24; P = .005).

Study details: Findings are from a meta-analysis of 11 studies including 2288 patients with BC who underwent breast reconstruction, of which 516 patients received PMRT after breast reconstruction.

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

Source: Huang N, Lu L, et al. Effect of radiation therapy during surgery on postoperative wound complications after breast reconstruction in patients with breast cancer: A meta-analysis. Int Wound J. 2023 (Oct 31). doi: 10.1111/iwj.14473

Key clinical point: Patients with breast cancer (BC) who underwent post-mastectomy breast reconstruction followed by post-mastectomy radiotherapy (PMRT) had an increased risk for postoperative complications, such as infections and contractures, than those who did not receive PMRT.

Major finding: Patients who did vs did not receive PMRT had a significantly higher risk for postoperative wound infections (odds ratio [OR] 1.95; P = .003) and skin contractures (OR 7.24; P = .005).

Study details: Findings are from a meta-analysis of 11 studies including 2288 patients with BC who underwent breast reconstruction, of which 516 patients received PMRT after breast reconstruction.

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

Source: Huang N, Lu L, et al. Effect of radiation therapy during surgery on postoperative wound complications after breast reconstruction in patients with breast cancer: A meta-analysis. Int Wound J. 2023 (Oct 31). doi: 10.1111/iwj.14473

Key clinical point: Patients with breast cancer (BC) who underwent post-mastectomy breast reconstruction followed by post-mastectomy radiotherapy (PMRT) had an increased risk for postoperative complications, such as infections and contractures, than those who did not receive PMRT.

Major finding: Patients who did vs did not receive PMRT had a significantly higher risk for postoperative wound infections (odds ratio [OR] 1.95; P = .003) and skin contractures (OR 7.24; P = .005).

Study details: Findings are from a meta-analysis of 11 studies including 2288 patients with BC who underwent breast reconstruction, of which 516 patients received PMRT after breast reconstruction.

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

Source: Huang N, Lu L, et al. Effect of radiation therapy during surgery on postoperative wound complications after breast reconstruction in patients with breast cancer: A meta-analysis. Int Wound J. 2023 (Oct 31). doi: 10.1111/iwj.14473

Key clinical point: Robotic nipple-sparing mastectomy (RNSM) may soon become a viable option for breast cancer (BC) surgery as it is associated with lower postoperative complication rates than conventional NSM (CNSM).

Major finding: RNSM vs CNSM was associated with a significantly lower rate of nipple necrosis, a major postoperative complication (odds ratio 0.54; P = .03), and intraoperative blood loss (mean difference [MD] −53.18 mL; P < .00001), but a significantly higher operating time (MD +58.81 min; P < .001).

Study details: Findings are from a meta-analysis of seven studies including 1674 women with BC who underwent RNSM (50.9%) or CNSM (49.1%).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nessa A et al. Postoperative complications and surgical outcomes of robotic versus conventional nipple-sparing mastectomy in breast cancer: Meta-analysis. Br J Surg. 2023 (Oct 27). doi: 10.1093/bjs/znad336

Key clinical point: Robotic nipple-sparing mastectomy (RNSM) may soon become a viable option for breast cancer (BC) surgery as it is associated with lower postoperative complication rates than conventional NSM (CNSM).

Major finding: RNSM vs CNSM was associated with a significantly lower rate of nipple necrosis, a major postoperative complication (odds ratio 0.54; P = .03), and intraoperative blood loss (mean difference [MD] −53.18 mL; P < .00001), but a significantly higher operating time (MD +58.81 min; P < .001).

Study details: Findings are from a meta-analysis of seven studies including 1674 women with BC who underwent RNSM (50.9%) or CNSM (49.1%).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nessa A et al. Postoperative complications and surgical outcomes of robotic versus conventional nipple-sparing mastectomy in breast cancer: Meta-analysis. Br J Surg. 2023 (Oct 27). doi: 10.1093/bjs/znad336

Key clinical point: Robotic nipple-sparing mastectomy (RNSM) may soon become a viable option for breast cancer (BC) surgery as it is associated with lower postoperative complication rates than conventional NSM (CNSM).

Major finding: RNSM vs CNSM was associated with a significantly lower rate of nipple necrosis, a major postoperative complication (odds ratio 0.54; P = .03), and intraoperative blood loss (mean difference [MD] −53.18 mL; P < .00001), but a significantly higher operating time (MD +58.81 min; P < .001).

Study details: Findings are from a meta-analysis of seven studies including 1674 women with BC who underwent RNSM (50.9%) or CNSM (49.1%).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nessa A et al. Postoperative complications and surgical outcomes of robotic versus conventional nipple-sparing mastectomy in breast cancer: Meta-analysis. Br J Surg. 2023 (Oct 27). doi: 10.1093/bjs/znad336

Key clinical point: Adjuvant chemotherapy significantly improved the overall survival (OS) outcomes in patients with small-size (T1b and T1c) node-negative triple-negative breast cancer (TNBC).

Major finding: Adjuvant chemotherapy led to significantly better OS outcomes in patients with T1b TNBC (adjusted hazard ratio [aHR] 0.52; P < .001) and improved both OS (aHR 0.54; P < .001) and breast cancer-specific survival (aHR 0.79; P = .043) in those with T1c TNBC.

Study details: This retrospective study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER) database and included 11,510 women with T1b (n = 3388) or T1c (n = 8122) node-negative TNBC, of whom 8029 patients received adjuvant chemotherapy.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Carbajal-Ochoa W et al. Benefit of adjuvant chemotherapy in lymph node-negative, T1b and T1c triple-negative breast cancer. Breast Cancer Res Treat. 2023 (Oct 13). doi: 10.1007/s10549-023-07132-6

Key clinical point: Adjuvant chemotherapy significantly improved the overall survival (OS) outcomes in patients with small-size (T1b and T1c) node-negative triple-negative breast cancer (TNBC).

Major finding: Adjuvant chemotherapy led to significantly better OS outcomes in patients with T1b TNBC (adjusted hazard ratio [aHR] 0.52; P < .001) and improved both OS (aHR 0.54; P < .001) and breast cancer-specific survival (aHR 0.79; P = .043) in those with T1c TNBC.

Study details: This retrospective study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER) database and included 11,510 women with T1b (n = 3388) or T1c (n = 8122) node-negative TNBC, of whom 8029 patients received adjuvant chemotherapy.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Carbajal-Ochoa W et al. Benefit of adjuvant chemotherapy in lymph node-negative, T1b and T1c triple-negative breast cancer. Breast Cancer Res Treat. 2023 (Oct 13). doi: 10.1007/s10549-023-07132-6

Key clinical point: Adjuvant chemotherapy significantly improved the overall survival (OS) outcomes in patients with small-size (T1b and T1c) node-negative triple-negative breast cancer (TNBC).

Major finding: Adjuvant chemotherapy led to significantly better OS outcomes in patients with T1b TNBC (adjusted hazard ratio [aHR] 0.52; P < .001) and improved both OS (aHR 0.54; P < .001) and breast cancer-specific survival (aHR 0.79; P = .043) in those with T1c TNBC.

Study details: This retrospective study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER) database and included 11,510 women with T1b (n = 3388) or T1c (n = 8122) node-negative TNBC, of whom 8029 patients received adjuvant chemotherapy.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Carbajal-Ochoa W et al. Benefit of adjuvant chemotherapy in lymph node-negative, T1b and T1c triple-negative breast cancer. Breast Cancer Res Treat. 2023 (Oct 13). doi: 10.1007/s10549-023-07132-6

Key clinical point: Pregnancy had no detrimental effects on survival outcomes and can be considered safe for young women who were previously diagnosed with and underwent treatment for hormone receptor-positive (HR+) early breast cancer (BC).

Major finding: Patients with a history of HR+ BC who did vs did not conceive after treatment showed better overall survival outcomes (hazard ratio 0.46; P < .005); however, the disease-free survival outcomes were comparable for both groups (P = .781).

Study details: Findings are from a meta-analysis of eight retrospective cohort studies including 3805 young women with HR+ invasive early BC, of whom 1285 women conceived post treatment.

Disclosures: This study was partially supported by the Italian Association for Cancer Research and the Italian Ministry of Health. Several authors declared receiving research support, honoraria, research funding, personal fees, grants, or consulting fees from or having ties with various sources.

Source: Arecco L et al. Safety of pregnancy after breast cancer in young women with hormone receptor-positive disease: A systematic review and meta-analysis. ESMO Open. 2023;8(6):102031 (Oct 23). doi: 10.1016/j.esmoop.2023.102031

Key clinical point: Pregnancy had no detrimental effects on survival outcomes and can be considered safe for young women who were previously diagnosed with and underwent treatment for hormone receptor-positive (HR+) early breast cancer (BC).

Major finding: Patients with a history of HR+ BC who did vs did not conceive after treatment showed better overall survival outcomes (hazard ratio 0.46; P < .005); however, the disease-free survival outcomes were comparable for both groups (P = .781).

Study details: Findings are from a meta-analysis of eight retrospective cohort studies including 3805 young women with HR+ invasive early BC, of whom 1285 women conceived post treatment.

Disclosures: This study was partially supported by the Italian Association for Cancer Research and the Italian Ministry of Health. Several authors declared receiving research support, honoraria, research funding, personal fees, grants, or consulting fees from or having ties with various sources.

Source: Arecco L et al. Safety of pregnancy after breast cancer in young women with hormone receptor-positive disease: A systematic review and meta-analysis. ESMO Open. 2023;8(6):102031 (Oct 23). doi: 10.1016/j.esmoop.2023.102031

Key clinical point: Pregnancy had no detrimental effects on survival outcomes and can be considered safe for young women who were previously diagnosed with and underwent treatment for hormone receptor-positive (HR+) early breast cancer (BC).

Major finding: Patients with a history of HR+ BC who did vs did not conceive after treatment showed better overall survival outcomes (hazard ratio 0.46; P < .005); however, the disease-free survival outcomes were comparable for both groups (P = .781).

Study details: Findings are from a meta-analysis of eight retrospective cohort studies including 3805 young women with HR+ invasive early BC, of whom 1285 women conceived post treatment.

Disclosures: This study was partially supported by the Italian Association for Cancer Research and the Italian Ministry of Health. Several authors declared receiving research support, honoraria, research funding, personal fees, grants, or consulting fees from or having ties with various sources.

Source: Arecco L et al. Safety of pregnancy after breast cancer in young women with hormone receptor-positive disease: A systematic review and meta-analysis. ESMO Open. 2023;8(6):102031 (Oct 23). doi: 10.1016/j.esmoop.2023.102031

Key clinical point: Detection of breast cancer (BC) by screening vs clinical or other non-screening procedures led to significantly improved disease-free interval outcomes.

Major finding: After correcting for lead time bias, the 10-year disease-free interval was improved significantly in women with screen-detected vs clinically-detected cancer (adjusted hazard ratio [aHR] 0.77; 95% CI 0.68-0.87), with similar improvements observed in 5-year disease-free interval in women with screen-detected vs non-screen-related cancer (aHR 0.76; 95% CI 0.66-0.88).

Study details: Findings are from an analysis of two cohorts including 6215 and 15,176 women with invasive, non-metastatic BC who underwent surgery and were followed for 10 and 5 years, respectively, of which 55.8% of women in either of the cohorts had a screen-detected cancer.

Disclosures: This study did not declare any specific funding. S Siesling declared receiving support and serving as an advisor for various sources. The other authors declared no conflicts of interest.

Source: de Munck L et al. Method of primary breast cancer detection and the disease-free interval, adjusting for lead time. J Natl Cancer Inst. 2023 (Nov 3). doi: 10.1093/jnci/djad230

Key clinical point: Detection of breast cancer (BC) by screening vs clinical or other non-screening procedures led to significantly improved disease-free interval outcomes.

Major finding: After correcting for lead time bias, the 10-year disease-free interval was improved significantly in women with screen-detected vs clinically-detected cancer (adjusted hazard ratio [aHR] 0.77; 95% CI 0.68-0.87), with similar improvements observed in 5-year disease-free interval in women with screen-detected vs non-screen-related cancer (aHR 0.76; 95% CI 0.66-0.88).

Study details: Findings are from an analysis of two cohorts including 6215 and 15,176 women with invasive, non-metastatic BC who underwent surgery and were followed for 10 and 5 years, respectively, of which 55.8% of women in either of the cohorts had a screen-detected cancer.

Disclosures: This study did not declare any specific funding. S Siesling declared receiving support and serving as an advisor for various sources. The other authors declared no conflicts of interest.

Source: de Munck L et al. Method of primary breast cancer detection and the disease-free interval, adjusting for lead time. J Natl Cancer Inst. 2023 (Nov 3). doi: 10.1093/jnci/djad230

Key clinical point: Detection of breast cancer (BC) by screening vs clinical or other non-screening procedures led to significantly improved disease-free interval outcomes.

Major finding: After correcting for lead time bias, the 10-year disease-free interval was improved significantly in women with screen-detected vs clinically-detected cancer (adjusted hazard ratio [aHR] 0.77; 95% CI 0.68-0.87), with similar improvements observed in 5-year disease-free interval in women with screen-detected vs non-screen-related cancer (aHR 0.76; 95% CI 0.66-0.88).

Study details: Findings are from an analysis of two cohorts including 6215 and 15,176 women with invasive, non-metastatic BC who underwent surgery and were followed for 10 and 5 years, respectively, of which 55.8% of women in either of the cohorts had a screen-detected cancer.

Disclosures: This study did not declare any specific funding. S Siesling declared receiving support and serving as an advisor for various sources. The other authors declared no conflicts of interest.

Source: de Munck L et al. Method of primary breast cancer detection and the disease-free interval, adjusting for lead time. J Natl Cancer Inst. 2023 (Nov 3). doi: 10.1093/jnci/djad230

Key clinical point: Although local transdermal therapy with 4-hydroxytamoxifen was associated with low systemic exposure, it was not as effective as oral tamoxifen in suppressing proliferation in the ductal carcinoma in situ (DCIS) lesions of the breast.

Major finding: Posttreatment Ki67 labelling index was significantly higher in the transdermal 4-hydroxytamoxifen gel vs oral tamoxifen treatment group (3.3%; 80% CI 2.1%-4.6%), with the value exceeding the noninferiority margin of 2.6%. Grade 2 adverse events were reported by five patients in both groups.

Study details: Findings are from a phase 2 study including 107 patients with DCIS of the breast who were randomly assigned to receive oral tamoxifen or 4-hydroxytamoxifen gel treatment for 4-10 weeks, of which 90 patients completed the treatment and underwent surgery.

Disclosures: This trial was sponsored by the US National Cancer Institute. Some authors declared receiving grant funding from various sources or holding a patent.

Source: Khan SA et al. Presurgical oral tamoxifen vs transdermal 4-hydroxytamoxifen in women with ductal carcinoma in situ: A randomized clinical trial. JAMA Surg. 2023 (Oct 23). doi: 10.1001/jamasurg.2023.5113

Key clinical point: Although local transdermal therapy with 4-hydroxytamoxifen was associated with low systemic exposure, it was not as effective as oral tamoxifen in suppressing proliferation in the ductal carcinoma in situ (DCIS) lesions of the breast.

Major finding: Posttreatment Ki67 labelling index was significantly higher in the transdermal 4-hydroxytamoxifen gel vs oral tamoxifen treatment group (3.3%; 80% CI 2.1%-4.6%), with the value exceeding the noninferiority margin of 2.6%. Grade 2 adverse events were reported by five patients in both groups.

Study details: Findings are from a phase 2 study including 107 patients with DCIS of the breast who were randomly assigned to receive oral tamoxifen or 4-hydroxytamoxifen gel treatment for 4-10 weeks, of which 90 patients completed the treatment and underwent surgery.

Disclosures: This trial was sponsored by the US National Cancer Institute. Some authors declared receiving grant funding from various sources or holding a patent.

Source: Khan SA et al. Presurgical oral tamoxifen vs transdermal 4-hydroxytamoxifen in women with ductal carcinoma in situ: A randomized clinical trial. JAMA Surg. 2023 (Oct 23). doi: 10.1001/jamasurg.2023.5113

Key clinical point: Although local transdermal therapy with 4-hydroxytamoxifen was associated with low systemic exposure, it was not as effective as oral tamoxifen in suppressing proliferation in the ductal carcinoma in situ (DCIS) lesions of the breast.

Major finding: Posttreatment Ki67 labelling index was significantly higher in the transdermal 4-hydroxytamoxifen gel vs oral tamoxifen treatment group (3.3%; 80% CI 2.1%-4.6%), with the value exceeding the noninferiority margin of 2.6%. Grade 2 adverse events were reported by five patients in both groups.

Study details: Findings are from a phase 2 study including 107 patients with DCIS of the breast who were randomly assigned to receive oral tamoxifen or 4-hydroxytamoxifen gel treatment for 4-10 weeks, of which 90 patients completed the treatment and underwent surgery.

Disclosures: This trial was sponsored by the US National Cancer Institute. Some authors declared receiving grant funding from various sources or holding a patent.

Source: Khan SA et al. Presurgical oral tamoxifen vs transdermal 4-hydroxytamoxifen in women with ductal carcinoma in situ: A randomized clinical trial. JAMA Surg. 2023 (Oct 23). doi: 10.1001/jamasurg.2023.5113

Key clinical point: Pyrotinib+trastuzumab+docetaxel was more effective than placebo+trastuzumab+docetaxel in improving progression-free survival (PFS) outcomes and showed a manageable safety profile in patients with untreated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: PFS improved by 59% with pyrotinib+trastuzumab+docetaxel vs placebo+trastuzumab+docetaxel treatment (24.3 vs 10.4 months; hazard ratio 0.41; stratified 1-sided P < .001). The most frequently reported grade ≥3 adverse events in the pyrotinib vs placebo treatment arm were decreased neutrophil count (63% vs 65%), decreased white blood cell count (53% vs 51%), and diarrhea (46% vs 3%).

Study details: Findings are from the phase 3 PHILA trial including 590 female patients with untreated HER2+ metastatic BC who were randomly assigned to receive pyrotinib or placebo, both in combination with trastuzumab and docetaxel.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals, China, and other sources. Three authors declared being employees of Jiangsu Hengrui Pharmaceuticals, and two other authors reported ties with various sources.

Source: Ma F et al, on behalf of the PHILA Investigators. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): Randomised, double blind, multicentre, phase 3 trial. BMJ. 2023;383:e076065 (Oct 31). doi: 10.1136/bmj-2023-076065

Key clinical point: Pyrotinib+trastuzumab+docetaxel was more effective than placebo+trastuzumab+docetaxel in improving progression-free survival (PFS) outcomes and showed a manageable safety profile in patients with untreated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: PFS improved by 59% with pyrotinib+trastuzumab+docetaxel vs placebo+trastuzumab+docetaxel treatment (24.3 vs 10.4 months; hazard ratio 0.41; stratified 1-sided P < .001). The most frequently reported grade ≥3 adverse events in the pyrotinib vs placebo treatment arm were decreased neutrophil count (63% vs 65%), decreased white blood cell count (53% vs 51%), and diarrhea (46% vs 3%).

Study details: Findings are from the phase 3 PHILA trial including 590 female patients with untreated HER2+ metastatic BC who were randomly assigned to receive pyrotinib or placebo, both in combination with trastuzumab and docetaxel.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals, China, and other sources. Three authors declared being employees of Jiangsu Hengrui Pharmaceuticals, and two other authors reported ties with various sources.

Source: Ma F et al, on behalf of the PHILA Investigators. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): Randomised, double blind, multicentre, phase 3 trial. BMJ. 2023;383:e076065 (Oct 31). doi: 10.1136/bmj-2023-076065

Key clinical point: Pyrotinib+trastuzumab+docetaxel was more effective than placebo+trastuzumab+docetaxel in improving progression-free survival (PFS) outcomes and showed a manageable safety profile in patients with untreated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: PFS improved by 59% with pyrotinib+trastuzumab+docetaxel vs placebo+trastuzumab+docetaxel treatment (24.3 vs 10.4 months; hazard ratio 0.41; stratified 1-sided P < .001). The most frequently reported grade ≥3 adverse events in the pyrotinib vs placebo treatment arm were decreased neutrophil count (63% vs 65%), decreased white blood cell count (53% vs 51%), and diarrhea (46% vs 3%).

Study details: Findings are from the phase 3 PHILA trial including 590 female patients with untreated HER2+ metastatic BC who were randomly assigned to receive pyrotinib or placebo, both in combination with trastuzumab and docetaxel.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals, China, and other sources. Three authors declared being employees of Jiangsu Hengrui Pharmaceuticals, and two other authors reported ties with various sources.

Source: Ma F et al, on behalf of the PHILA Investigators. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): Randomised, double blind, multicentre, phase 3 trial. BMJ. 2023;383:e076065 (Oct 31). doi: 10.1136/bmj-2023-076065