Clinical Edge Journal Scan Commentary

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

Among the patients treated with trastuzumab deruxtecan, median progression-free survival was significantly prolonged compared with the physician's choice treatment group (17.8 vs 6.9 months; hazard ratio 0.36; P < .0001). There were no new safety signals reported for trastuzumab deruxtecan. Of interest, drug-related interstitial lung disease occurred in 10% of patients treated with trastuzumab deruxtecan (including two grade 5 death events) compared with < 1% in the physician's-choice treatment group.

Overall, trastuzumab deruxtecan demonstrated a favorable benefit-risk profile in patients with HER2+ BC previously treated with trastuzumab emtansine. This is the first randomized study to show efficacy with an antibody-drug conjugate after a previous antibody-drug conjugate.

Breast density is a known independent risk factor for BC, furthermore, dense breast tissue can make identifying BC on screening mammograms more challenging. The nested case-control cohort study by Jiang and colleagues observed women with no history of any cancer for 10 years, with screening mammograms every 1-2 years. Subsequently, 289 women who developed BC were identified and analyzed along with 658 matched control individuals. BC risk factors were also collected via questionnaires at the time of enrollment. Of note, the BC cases cohort had an overall higher mean body mass index, a higher percentage of Black women, and of women with a family history of BC. The results showed that though women's breast density decreased over time in both cases and controls, the rate of change in breast density was significantly slower in the breast that later developed cancer compared with the cancer-free breast in control individuals (estimate 0.027; P = .04). Enhancing screening modalities to enable assessing for longitudinal changes in breast density may provide an additional tool for evaluating the risk for BC.

Reducing the late BC recurrence risk beyond 5 years is a significant issue in patients with hormone receptor–positive (HR+) BC. This prospective, randomized, phase 3, AERAS trial included 1593 postmenopausal women with HR+ early-stage invasive BC who were disease-free at 5 years after postoperative endocrine therapy. Patients were randomly assigned 1:1 to stop or continue receiving anastrozole for an additional 5 years. Results showed that continuation of anastrozole treatment for an additional 5 years significantly improved 5-year disease-free survival (DFS) (hazard ratio 0.61; 95% CI 0.46-0.82; P < .0010). Furthermore, extended anastrozole treatment reduced the incidence of local recurrence and second primary cancers. However, there was no significant difference in distant DFS. The incidence of grade 3 or higher adverse events was < 1% in both groups, although menopausal or bone-related all-grade adverse events were more frequent among patients in the group that continued with anastrozole, as expected. Results from this study help inform the risks and benefits of extending hormone therapy beyond 5 years.

The RxPONDER trial comparing endocrine therapy (ET) alone to chemotherapy plus endocrine therapy (CET) in patients with one to three positive axillary lymph nodes and recurrence score (RS) ≤ 25 showed that CET did not improve survival outcomes compared with ET alone in postmenopausal women with HR+/HER2- BC. This retrospective cohort study of real-world data from the National Cancer Database included 28,427 women with stage I-III HR+/HER2- BC and one to three positive axillary lymph nodes, of which 26.3% and 73.7% of patients received CET and ET, respectively. Results showed that in patients with RS of 20-25, CET was associated with a significant improvement in overall survival compared with ET alone, in both premenopausal (age ≤ 50 years: hazard ratio 0.334, P = .002) and postmenopausal patients (age > 50 years: hazard ratio 0.521, P = .019). Though these results are inconsistent with the RxPONDER trial results regarding the postmenopausal cohort, they do raise an important finding that is supported by prior published data.¹ More studies are needed to validate these findings. At this time, guidelines recommend omitting chemotherapy in patients with HR+/HER2- BC, one to three positive axillary lymph nodes, and an RS of 20-25 per RxPONDER.

Additional Reference

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. doi: 10.1016/S0140-6736(11)61625-5

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

Diffuse large B-cell lymphoma (DLBCL) is both a clinically and molecularly heterogenous disease. The International Prognostic Index (IPI), which is based on clinical and laboratory variables, is still currently used to delineate risk at the time of diagnosis. Diffuse large B-cell lymphoma can also further be classified into either germinal center B-cell (GCB) or activated B-cell (ABC) subtype, also known as the cell-of-origin classification (COO), which has been prognostic in prior studies.¹ COO is based on gene expression profiling (GEP), though it can be estimated by immunohistochemistry.

Although these classifications are available, treatment of DLBCL has largely remained uniform over the past few decades. Despite encouraging preclinical data and early trials, large randomized studies had not demonstrated an advantage of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) plus X over R-CHOP alone.^2,3 The REMoDL-B trial, which included 801 adult patients with DLBCL, including patients with ABC, GCB, or molecular high grade (MHG) classification by GEP. Patients received one cycle of R-CHOP and were randomly assigned to R-CHOP (n = 407) alone or bortezomib–R-CHOP (n = 394) for cycles 2-6. Initial reports did not demonstrate any clear benefit of the addition of bortezomib.⁴ More recently, however, 5-year follow-up data demonstrate that the addition of bortezomib confers an advantage over R-CHOP in patients with ABC and MHG DLBCL (Davies et al). Bortezomib–R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P = .041) and MHG (aHR 0.46; P = .011) groups and overall survival (OS) in the ABC group (aHR 0.58; P = .032). The GCB group showed no significant difference in PFS or OS.

Despite the results of REMoDL-B, it is unlikely that this study will change practice. GEP is not readily available and with the approval of polatuzumab (pola)–R-CHP, based on the results of POLARIX trial, there is new option available for patients with newly diagnosed DLBCL with a high IPI. A recent meta-analysis of 12 randomized controlled trials (Sheng et al) involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received pola–R-CHP or other regimens was also recently performed. This study showed that pola–R-CHP prolonged PFS in patients with ABC-type DLBCL compared with bortezomib–R-CHOP (hazard ratio [HR] 0.52; P = .02); ibrutinib–R-CHOP (HR 0.43; P = .001); lenalidomide–R-CHOP (HR 0.51; P = .009); Obinutuzumab–CHOP (HR 0.46; P = .008); R-CHOP (HR 0.40; P < .001); and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P = .07). Pola–R-CHP had no PFS benefit in patients with GCB-type DLBCL. Although it is difficult to directly compare trials, these data suggest that pola–R-CHP is active in ABC subtype DLBCL.

Together, these trials suggest that there still may be a role for more personalized therapy in DLBCL, though there may be room for improvement. Recent studies have suggested more complex genomic underpinnings in DLBCL beyond COO, which will hopefully be studied in the context of DLBCL trials.⁵

In the second line, patients with primary refractory or early relapse of DLBCL now have the option of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, based on the results of the ZUMA-7 and TRANSFORM studies.^6,7 Lisocabtagene maraleucel (liso-cel) was also found to have a manageable safety profile in older patients with large B-cell lymphoma who were not transplant candidates in the PILOT study, leading to approval in this setting.⁸ More recently, axicabtagene ciloleucel (axi-cel) was found to be an effective second-line therapy with a manageable safety profile for patients aged ≥ 65 years as well (Westin et al). These findings are from a preplanned analysis of 109 patients aged ≥ 65 years from ZUMA-7 who were randomly assigned to receive second-line axi-cel (n = 51) or standard of care (SOC) (n = 58; two or three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation). At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs SOC; 21.5 vs 2.5 months; HR, 0.276; descriptive P < .0001). Rates of grade 3 or higher treatment-emergent adverse events were 94% and 82% with axi-cel and SOC, respectively. Although these patients were considered transplant eligible, this study demonstrates that axi-cel can be safely administered to older patients.

Additional References

1.         Rosenwald A, Wright G, Chan WC, et al; Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937-1947. doi: 10.1056/NEJMoa012914

2.         Younes A, Sehn LH, Johnson P, et al; PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019;37:1285-1295. doi: 10.1200/JCO.18.02403

3.         Nowakowski GS, Chiappella A, Gascoyne RD, et al; ROBUST Trial Investigators. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39:1317-1328. doi: 10.1200/JCO.20.01366

4.         Davies A, Cummin TE, Barrans S, et al. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20:649-662. doi: 10.1016/S1470-2045(18)30935-5

5.         Crombie JL, Armand P. Diffuse large B-cell lymphoma's new genomics: the bridge and the chasm. J Clin Oncol. 2020;38:3565-3574. doi: 10.1200/JCO.20.01501

6.         Locke FL, Miklos DB, Jacobson CA, et al for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133

7.         Abramson JS, Solomon SR, Arnason JE, et al; TRANSFORM Investigators. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of phase 3 TRANSFORM study. Blood. 2023:141:1675-1684. doi: 10.1182/blood.2022018730

8.         Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23:1066-1077. doi: 10.1016/S1470-2045(22)00339-4

Diffuse large B-cell lymphoma (DLBCL) is both a clinically and molecularly heterogenous disease. The International Prognostic Index (IPI), which is based on clinical and laboratory variables, is still currently used to delineate risk at the time of diagnosis. Diffuse large B-cell lymphoma can also further be classified into either germinal center B-cell (GCB) or activated B-cell (ABC) subtype, also known as the cell-of-origin classification (COO), which has been prognostic in prior studies.¹ COO is based on gene expression profiling (GEP), though it can be estimated by immunohistochemistry.

Although these classifications are available, treatment of DLBCL has largely remained uniform over the past few decades. Despite encouraging preclinical data and early trials, large randomized studies had not demonstrated an advantage of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) plus X over R-CHOP alone.^2,3 The REMoDL-B trial, which included 801 adult patients with DLBCL, including patients with ABC, GCB, or molecular high grade (MHG) classification by GEP. Patients received one cycle of R-CHOP and were randomly assigned to R-CHOP (n = 407) alone or bortezomib–R-CHOP (n = 394) for cycles 2-6. Initial reports did not demonstrate any clear benefit of the addition of bortezomib.⁴ More recently, however, 5-year follow-up data demonstrate that the addition of bortezomib confers an advantage over R-CHOP in patients with ABC and MHG DLBCL (Davies et al). Bortezomib–R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P = .041) and MHG (aHR 0.46; P = .011) groups and overall survival (OS) in the ABC group (aHR 0.58; P = .032). The GCB group showed no significant difference in PFS or OS.

Despite the results of REMoDL-B, it is unlikely that this study will change practice. GEP is not readily available and with the approval of polatuzumab (pola)–R-CHP, based on the results of POLARIX trial, there is new option available for patients with newly diagnosed DLBCL with a high IPI. A recent meta-analysis of 12 randomized controlled trials (Sheng et al) involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received pola–R-CHP or other regimens was also recently performed. This study showed that pola–R-CHP prolonged PFS in patients with ABC-type DLBCL compared with bortezomib–R-CHOP (hazard ratio [HR] 0.52; P = .02); ibrutinib–R-CHOP (HR 0.43; P = .001); lenalidomide–R-CHOP (HR 0.51; P = .009); Obinutuzumab–CHOP (HR 0.46; P = .008); R-CHOP (HR 0.40; P < .001); and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P = .07). Pola–R-CHP had no PFS benefit in patients with GCB-type DLBCL. Although it is difficult to directly compare trials, these data suggest that pola–R-CHP is active in ABC subtype DLBCL.

Together, these trials suggest that there still may be a role for more personalized therapy in DLBCL, though there may be room for improvement. Recent studies have suggested more complex genomic underpinnings in DLBCL beyond COO, which will hopefully be studied in the context of DLBCL trials.⁵

In the second line, patients with primary refractory or early relapse of DLBCL now have the option of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, based on the results of the ZUMA-7 and TRANSFORM studies.^6,7 Lisocabtagene maraleucel (liso-cel) was also found to have a manageable safety profile in older patients with large B-cell lymphoma who were not transplant candidates in the PILOT study, leading to approval in this setting.⁸ More recently, axicabtagene ciloleucel (axi-cel) was found to be an effective second-line therapy with a manageable safety profile for patients aged ≥ 65 years as well (Westin et al). These findings are from a preplanned analysis of 109 patients aged ≥ 65 years from ZUMA-7 who were randomly assigned to receive second-line axi-cel (n = 51) or standard of care (SOC) (n = 58; two or three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation). At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs SOC; 21.5 vs 2.5 months; HR, 0.276; descriptive P < .0001). Rates of grade 3 or higher treatment-emergent adverse events were 94% and 82% with axi-cel and SOC, respectively. Although these patients were considered transplant eligible, this study demonstrates that axi-cel can be safely administered to older patients.

Additional References

1.         Rosenwald A, Wright G, Chan WC, et al; Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937-1947. doi: 10.1056/NEJMoa012914

2.         Younes A, Sehn LH, Johnson P, et al; PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019;37:1285-1295. doi: 10.1200/JCO.18.02403

3.         Nowakowski GS, Chiappella A, Gascoyne RD, et al; ROBUST Trial Investigators. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39:1317-1328. doi: 10.1200/JCO.20.01366

4.         Davies A, Cummin TE, Barrans S, et al. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20:649-662. doi: 10.1016/S1470-2045(18)30935-5

5.         Crombie JL, Armand P. Diffuse large B-cell lymphoma's new genomics: the bridge and the chasm. J Clin Oncol. 2020;38:3565-3574. doi: 10.1200/JCO.20.01501

6.         Locke FL, Miklos DB, Jacobson CA, et al for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133

7.         Abramson JS, Solomon SR, Arnason JE, et al; TRANSFORM Investigators. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of phase 3 TRANSFORM study. Blood. 2023:141:1675-1684. doi: 10.1182/blood.2022018730

8.         Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23:1066-1077. doi: 10.1016/S1470-2045(22)00339-4

Diffuse large B-cell lymphoma (DLBCL) is both a clinically and molecularly heterogenous disease. The International Prognostic Index (IPI), which is based on clinical and laboratory variables, is still currently used to delineate risk at the time of diagnosis. Diffuse large B-cell lymphoma can also further be classified into either germinal center B-cell (GCB) or activated B-cell (ABC) subtype, also known as the cell-of-origin classification (COO), which has been prognostic in prior studies.¹ COO is based on gene expression profiling (GEP), though it can be estimated by immunohistochemistry.

Although these classifications are available, treatment of DLBCL has largely remained uniform over the past few decades. Despite encouraging preclinical data and early trials, large randomized studies had not demonstrated an advantage of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) plus X over R-CHOP alone.^2,3 The REMoDL-B trial, which included 801 adult patients with DLBCL, including patients with ABC, GCB, or molecular high grade (MHG) classification by GEP. Patients received one cycle of R-CHOP and were randomly assigned to R-CHOP (n = 407) alone or bortezomib–R-CHOP (n = 394) for cycles 2-6. Initial reports did not demonstrate any clear benefit of the addition of bortezomib.⁴ More recently, however, 5-year follow-up data demonstrate that the addition of bortezomib confers an advantage over R-CHOP in patients with ABC and MHG DLBCL (Davies et al). Bortezomib–R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P = .041) and MHG (aHR 0.46; P = .011) groups and overall survival (OS) in the ABC group (aHR 0.58; P = .032). The GCB group showed no significant difference in PFS or OS.

Despite the results of REMoDL-B, it is unlikely that this study will change practice. GEP is not readily available and with the approval of polatuzumab (pola)–R-CHP, based on the results of POLARIX trial, there is new option available for patients with newly diagnosed DLBCL with a high IPI. A recent meta-analysis of 12 randomized controlled trials (Sheng et al) involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received pola–R-CHP or other regimens was also recently performed. This study showed that pola–R-CHP prolonged PFS in patients with ABC-type DLBCL compared with bortezomib–R-CHOP (hazard ratio [HR] 0.52; P = .02); ibrutinib–R-CHOP (HR 0.43; P = .001); lenalidomide–R-CHOP (HR 0.51; P = .009); Obinutuzumab–CHOP (HR 0.46; P = .008); R-CHOP (HR 0.40; P < .001); and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P = .07). Pola–R-CHP had no PFS benefit in patients with GCB-type DLBCL. Although it is difficult to directly compare trials, these data suggest that pola–R-CHP is active in ABC subtype DLBCL.

Together, these trials suggest that there still may be a role for more personalized therapy in DLBCL, though there may be room for improvement. Recent studies have suggested more complex genomic underpinnings in DLBCL beyond COO, which will hopefully be studied in the context of DLBCL trials.⁵

In the second line, patients with primary refractory or early relapse of DLBCL now have the option of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, based on the results of the ZUMA-7 and TRANSFORM studies.^6,7 Lisocabtagene maraleucel (liso-cel) was also found to have a manageable safety profile in older patients with large B-cell lymphoma who were not transplant candidates in the PILOT study, leading to approval in this setting.⁸ More recently, axicabtagene ciloleucel (axi-cel) was found to be an effective second-line therapy with a manageable safety profile for patients aged ≥ 65 years as well (Westin et al). These findings are from a preplanned analysis of 109 patients aged ≥ 65 years from ZUMA-7 who were randomly assigned to receive second-line axi-cel (n = 51) or standard of care (SOC) (n = 58; two or three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation). At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs SOC; 21.5 vs 2.5 months; HR, 0.276; descriptive P < .0001). Rates of grade 3 or higher treatment-emergent adverse events were 94% and 82% with axi-cel and SOC, respectively. Although these patients were considered transplant eligible, this study demonstrates that axi-cel can be safely administered to older patients.

Additional References

1.         Rosenwald A, Wright G, Chan WC, et al; Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937-1947. doi: 10.1056/NEJMoa012914

2.         Younes A, Sehn LH, Johnson P, et al; PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019;37:1285-1295. doi: 10.1200/JCO.18.02403

3.         Nowakowski GS, Chiappella A, Gascoyne RD, et al; ROBUST Trial Investigators. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39:1317-1328. doi: 10.1200/JCO.20.01366

4.         Davies A, Cummin TE, Barrans S, et al. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20:649-662. doi: 10.1016/S1470-2045(18)30935-5

5.         Crombie JL, Armand P. Diffuse large B-cell lymphoma's new genomics: the bridge and the chasm. J Clin Oncol. 2020;38:3565-3574. doi: 10.1200/JCO.20.01501

6.         Locke FL, Miklos DB, Jacobson CA, et al for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133

7.         Abramson JS, Solomon SR, Arnason JE, et al; TRANSFORM Investigators. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of phase 3 TRANSFORM study. Blood. 2023:141:1675-1684. doi: 10.1182/blood.2022018730

8.         Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23:1066-1077. doi: 10.1016/S1470-2045(22)00339-4

A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.

Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia

Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.

Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC

Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI  0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.

A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.

Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia

Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.

Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC

Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI  0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.

A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.

Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia

Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.

Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC

Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI  0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.

Although rheumatoid arthritis (RA) is well understood to be associated with cigarette smoking as well as with a risk for interstitial lung disease (ILD), its association with airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and with allergic disorders such as atopic dermatitis and allergic rhinitis, is unknown. Kim and colleagues performed a cross-sectional study using information from the Korean National Health and Nutrition Examination Survey by 334 respondents with RA and over 13,000 respondents without RA and analyzed the association of RA with asthma and asthma-related comorbidities. The prevalence of asthma was higher in respondents with RA (7.5% vs 2.8%; P < .001), but the prevalence of other allergic disorders and COPD wassimilar between groups. This finding in a small group of respondents is not striking and its importance is unclear compared with other nonallergic pulmonary disorders. Inferring a mechanistic connection to T-helper (Th) 1- vs Th2 immunity would thus be premature.

Baker and colleagues examined the risk for RA-associated ILD in patients taking different therapies for RA, a topic of great interest due to the frequency of this complication as well as uncertainty regarding its association with medications, including anti-tumor necrosis factor (TNF) agents and methotrexate. Using a claims database, they performed a retrospective study of patients with RA without existing ILD who were treated with a biologic (b) or targeted synthetic disease-modifying antirheumatic drugs (DMARD; abatacept, adalimumab, rituximab, tocilizumab, and tofacitinib). In over 28,000 patients with RA, incidence ratios for ILD were > 1 for all bDMARD, while the incidence ratio for ILD with tofacitinib was 1.47. As the group of patients treated with tofacitinib was the smallest, the reliability of this result is uncertain and thus not strong enough to suggest a protective effect or preference for this medication in patients with known ILD. However, prospective studies looking at ILD in RA patients taking tofacitinib would be of interest.

Kristensen and colleagues also looked at risks associated with tofacitinib and anti-TNF agents, in particular cardiovascular disease, malignancy, and venous thromboembolism, using data from the open-label randomized ORAL Surveillance study, which looked at patients taking 5 mg or 10 mg tofacitinib twice daily, adalimumab, or etanercept. The 10 mg dose was reduced to 5 mg twice daily after it was found that rates of pulmonary embolism were higher in the group taking the higher dose. Age and smoking are also known to be risk factors for malignancy and cardiovascular disease in patients with RA, and these findings carried through in this analysis as well. Within the study, patients taking tofacitinib over age 65 who had ever smoked had a higher risk for cardiovascular events, myocardial infarction, malignancy, venous thromboembolism, and death compared with patients on anti-TNF therapy, while patients taking tofacitinib who were younger than 65 and had never smoked had a risk similar to those on anti-TNF therapy.The study confirms prior knowledge regarding the risks of tofacitinib in different patient populations, suggesting that caution should be used with this medication in older patients and those who smoke.

Although rheumatoid arthritis (RA) is well understood to be associated with cigarette smoking as well as with a risk for interstitial lung disease (ILD), its association with airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and with allergic disorders such as atopic dermatitis and allergic rhinitis, is unknown. Kim and colleagues performed a cross-sectional study using information from the Korean National Health and Nutrition Examination Survey by 334 respondents with RA and over 13,000 respondents without RA and analyzed the association of RA with asthma and asthma-related comorbidities. The prevalence of asthma was higher in respondents with RA (7.5% vs 2.8%; P < .001), but the prevalence of other allergic disorders and COPD wassimilar between groups. This finding in a small group of respondents is not striking and its importance is unclear compared with other nonallergic pulmonary disorders. Inferring a mechanistic connection to T-helper (Th) 1- vs Th2 immunity would thus be premature.

Baker and colleagues examined the risk for RA-associated ILD in patients taking different therapies for RA, a topic of great interest due to the frequency of this complication as well as uncertainty regarding its association with medications, including anti-tumor necrosis factor (TNF) agents and methotrexate. Using a claims database, they performed a retrospective study of patients with RA without existing ILD who were treated with a biologic (b) or targeted synthetic disease-modifying antirheumatic drugs (DMARD; abatacept, adalimumab, rituximab, tocilizumab, and tofacitinib). In over 28,000 patients with RA, incidence ratios for ILD were > 1 for all bDMARD, while the incidence ratio for ILD with tofacitinib was 1.47. As the group of patients treated with tofacitinib was the smallest, the reliability of this result is uncertain and thus not strong enough to suggest a protective effect or preference for this medication in patients with known ILD. However, prospective studies looking at ILD in RA patients taking tofacitinib would be of interest.

Kristensen and colleagues also looked at risks associated with tofacitinib and anti-TNF agents, in particular cardiovascular disease, malignancy, and venous thromboembolism, using data from the open-label randomized ORAL Surveillance study, which looked at patients taking 5 mg or 10 mg tofacitinib twice daily, adalimumab, or etanercept. The 10 mg dose was reduced to 5 mg twice daily after it was found that rates of pulmonary embolism were higher in the group taking the higher dose. Age and smoking are also known to be risk factors for malignancy and cardiovascular disease in patients with RA, and these findings carried through in this analysis as well. Within the study, patients taking tofacitinib over age 65 who had ever smoked had a higher risk for cardiovascular events, myocardial infarction, malignancy, venous thromboembolism, and death compared with patients on anti-TNF therapy, while patients taking tofacitinib who were younger than 65 and had never smoked had a risk similar to those on anti-TNF therapy.The study confirms prior knowledge regarding the risks of tofacitinib in different patient populations, suggesting that caution should be used with this medication in older patients and those who smoke.

Although rheumatoid arthritis (RA) is well understood to be associated with cigarette smoking as well as with a risk for interstitial lung disease (ILD), its association with airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and with allergic disorders such as atopic dermatitis and allergic rhinitis, is unknown. Kim and colleagues performed a cross-sectional study using information from the Korean National Health and Nutrition Examination Survey by 334 respondents with RA and over 13,000 respondents without RA and analyzed the association of RA with asthma and asthma-related comorbidities. The prevalence of asthma was higher in respondents with RA (7.5% vs 2.8%; P < .001), but the prevalence of other allergic disorders and COPD wassimilar between groups. This finding in a small group of respondents is not striking and its importance is unclear compared with other nonallergic pulmonary disorders. Inferring a mechanistic connection to T-helper (Th) 1- vs Th2 immunity would thus be premature.

Baker and colleagues examined the risk for RA-associated ILD in patients taking different therapies for RA, a topic of great interest due to the frequency of this complication as well as uncertainty regarding its association with medications, including anti-tumor necrosis factor (TNF) agents and methotrexate. Using a claims database, they performed a retrospective study of patients with RA without existing ILD who were treated with a biologic (b) or targeted synthetic disease-modifying antirheumatic drugs (DMARD; abatacept, adalimumab, rituximab, tocilizumab, and tofacitinib). In over 28,000 patients with RA, incidence ratios for ILD were > 1 for all bDMARD, while the incidence ratio for ILD with tofacitinib was 1.47. As the group of patients treated with tofacitinib was the smallest, the reliability of this result is uncertain and thus not strong enough to suggest a protective effect or preference for this medication in patients with known ILD. However, prospective studies looking at ILD in RA patients taking tofacitinib would be of interest.

Kristensen and colleagues also looked at risks associated with tofacitinib and anti-TNF agents, in particular cardiovascular disease, malignancy, and venous thromboembolism, using data from the open-label randomized ORAL Surveillance study, which looked at patients taking 5 mg or 10 mg tofacitinib twice daily, adalimumab, or etanercept. The 10 mg dose was reduced to 5 mg twice daily after it was found that rates of pulmonary embolism were higher in the group taking the higher dose. Age and smoking are also known to be risk factors for malignancy and cardiovascular disease in patients with RA, and these findings carried through in this analysis as well. Within the study, patients taking tofacitinib over age 65 who had ever smoked had a higher risk for cardiovascular events, myocardial infarction, malignancy, venous thromboembolism, and death compared with patients on anti-TNF therapy, while patients taking tofacitinib who were younger than 65 and had never smoked had a risk similar to those on anti-TNF therapy.The study confirms prior knowledge regarding the risks of tofacitinib in different patient populations, suggesting that caution should be used with this medication in older patients and those who smoke.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.

Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.² A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.

The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.³ A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.

Additional References

1. De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
2. Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
3. Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017

Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.

Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.² A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.

The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.³ A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.

Additional References

1. De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
2. Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
3. Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017

Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.

Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.² A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.

The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.³ A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.

Additional References

1. De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
2. Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
3. Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017