Key clinical point: In postmenopausal women with early-stage hormone receptor-positive (HR+) breast cancer (BC) who were disease free after 5 years of endocrine therapy (ET), extended adjuvant treatment with letrozole for 5 years led to improved disease-free survival (DFS) at >10-year median follow-up.

Major finding: After median follow-up of 10.3 years, letrozole vs placebo significantly improved DFS (10-year absolute benefit 3.4%; hazard ratio 0.85; P = .01). There were no notable differences in toxicity outcomes between the groups.

Study details: Findings are from the phase 3 National Surgical Adjuvant Breast and Bowel Project B-42 trial including 3966 postmenopausal women with stage I-IIIA HR+ BC who were disease free after 5 years of adjuvant ET and were randomly assigned to receive letrozole or placebo for 5 more years.

Disclosures: This study was funded by Novartis and others. Some authors declared receiving grants, honoraria, travel support, or consulting fees or serving on advisory boards or data and safety monitoring boards for various sources, including Novartis.

Source: Mamounas EP et al. Ten-year update: NRG Oncology/NSABP B-42 randomized trial: Extended letrozole therapy in early-stage breast cancer. J Natl Cancer Inst. 2023 (May 15). doi: 10.1093/jnci/djad078

Key clinical point: In postmenopausal women with early-stage hormone receptor-positive (HR+) breast cancer (BC) who were disease free after 5 years of endocrine therapy (ET), extended adjuvant treatment with letrozole for 5 years led to improved disease-free survival (DFS) at >10-year median follow-up.

Major finding: After median follow-up of 10.3 years, letrozole vs placebo significantly improved DFS (10-year absolute benefit 3.4%; hazard ratio 0.85; P = .01). There were no notable differences in toxicity outcomes between the groups.

Study details: Findings are from the phase 3 National Surgical Adjuvant Breast and Bowel Project B-42 trial including 3966 postmenopausal women with stage I-IIIA HR+ BC who were disease free after 5 years of adjuvant ET and were randomly assigned to receive letrozole or placebo for 5 more years.

Disclosures: This study was funded by Novartis and others. Some authors declared receiving grants, honoraria, travel support, or consulting fees or serving on advisory boards or data and safety monitoring boards for various sources, including Novartis.

Source: Mamounas EP et al. Ten-year update: NRG Oncology/NSABP B-42 randomized trial: Extended letrozole therapy in early-stage breast cancer. J Natl Cancer Inst. 2023 (May 15). doi: 10.1093/jnci/djad078

Key clinical point: In postmenopausal women with early-stage hormone receptor-positive (HR+) breast cancer (BC) who were disease free after 5 years of endocrine therapy (ET), extended adjuvant treatment with letrozole for 5 years led to improved disease-free survival (DFS) at >10-year median follow-up.

Major finding: After median follow-up of 10.3 years, letrozole vs placebo significantly improved DFS (10-year absolute benefit 3.4%; hazard ratio 0.85; P = .01). There were no notable differences in toxicity outcomes between the groups.

Study details: Findings are from the phase 3 National Surgical Adjuvant Breast and Bowel Project B-42 trial including 3966 postmenopausal women with stage I-IIIA HR+ BC who were disease free after 5 years of adjuvant ET and were randomly assigned to receive letrozole or placebo for 5 more years.

Disclosures: This study was funded by Novartis and others. Some authors declared receiving grants, honoraria, travel support, or consulting fees or serving on advisory boards or data and safety monitoring boards for various sources, including Novartis.

Source: Mamounas EP et al. Ten-year update: NRG Oncology/NSABP B-42 randomized trial: Extended letrozole therapy in early-stage breast cancer. J Natl Cancer Inst. 2023 (May 15). doi: 10.1093/jnci/djad078

Key clinical point: Adding cyclin-dependent kinase 4/6 (CDK4/6) inhibitors to endocrine therapy (ET) improved survival outcomes in elderly patients aged ≥65 years with advanced estrogen receptor-positive (ER+) breast cancer (BC).

Major finding: Adding CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced the mortality risk by 21% (hazard ratio [HR] 0.79; 95% CI 0.69-0.91) and progression risk by 41% (HR 0.59; 95% CI 0.51-0.69) in older patients aged >65 years with BC.

Study details: Findings are from a meta-analysis of 10 trials including 1985 older patients with advanced ER+ BC who received ET with or without CDK4/6 inhibitors.

Disclosures: This study did not report the source of funding. The authors did not declare any conflicts of interest.

Source: Petrelli F et al. The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis. Breast. 2023 (May 12). doi: 10.1016/j.breast.2023.05.002

Key clinical point: Adding cyclin-dependent kinase 4/6 (CDK4/6) inhibitors to endocrine therapy (ET) improved survival outcomes in elderly patients aged ≥65 years with advanced estrogen receptor-positive (ER+) breast cancer (BC).

Major finding: Adding CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced the mortality risk by 21% (hazard ratio [HR] 0.79; 95% CI 0.69-0.91) and progression risk by 41% (HR 0.59; 95% CI 0.51-0.69) in older patients aged >65 years with BC.

Study details: Findings are from a meta-analysis of 10 trials including 1985 older patients with advanced ER+ BC who received ET with or without CDK4/6 inhibitors.

Disclosures: This study did not report the source of funding. The authors did not declare any conflicts of interest.

Source: Petrelli F et al. The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis. Breast. 2023 (May 12). doi: 10.1016/j.breast.2023.05.002

Key clinical point: Adding cyclin-dependent kinase 4/6 (CDK4/6) inhibitors to endocrine therapy (ET) improved survival outcomes in elderly patients aged ≥65 years with advanced estrogen receptor-positive (ER+) breast cancer (BC).

Major finding: Adding CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced the mortality risk by 21% (hazard ratio [HR] 0.79; 95% CI 0.69-0.91) and progression risk by 41% (HR 0.59; 95% CI 0.51-0.69) in older patients aged >65 years with BC.

Study details: Findings are from a meta-analysis of 10 trials including 1985 older patients with advanced ER+ BC who received ET with or without CDK4/6 inhibitors.

Disclosures: This study did not report the source of funding. The authors did not declare any conflicts of interest.

Source: Petrelli F et al. The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis. Breast. 2023 (May 12). doi: 10.1016/j.breast.2023.05.002

An oral oil containing tetrahydrocannabinol (THC) and cannabidiol (CBD) led to a significant and meaningful reduction in motor and vocal tics in patients with severe Tourette syndrome (TS), results of a double-blind, placebo-controlled, crossover study show.

“In a methodologically robust manner (and independent of any drug company sponsorship), we provide evidence for the effectiveness of repeated dosing with THC:CBD vs. placebo in tic suppression, as well as reduction of comorbid anxiety and obsessive-compulsive disorder in severe TS,” neuropsychiatrist and lead investigator Philip Mosley, PhD, said in an interview.

The results offer support to people with TS who “want to approach their doctor to try medicinal cannabis when other drugs have not worked or are intolerable,” said Dr. Mosley, of the Wesley Research Institute and QIMR Berghofer Medical Research Institute, Herston, Australia.

The study was published online in NEJM Evidence.
 

A viable treatment option

Twenty-two adults (mean age, 31 years) with severe TS received THC:CBD oil titrated upward over 6 weeks to a daily dose of 20 mg of THC and 20 mg of CBD, followed by a 6-week course of placebo (or vice versa). Six participants had not previously used cannabis.

The primary outcome was the total tic score on the Yale Global Tic Severity Scale (YGTSS; range 0 to 50 with higher scores = greater tic severity).

The mean baseline YGTSS total tic score was 35.7. At 6 weeks, the reduction in total tic score was 8.9 with THC:CBD vs. 2.5 with placebo.

A linear mixed-effects model (intention-to-treat) showed a significant interaction of treatment and visit number (P = .008), indicating a greater decrease (improvement) in tic score over time with THC:CBD, the study team reported.

On average, the magnitude of the tic reduction was “moderate” and comparable to the effect observed with existing treatments such as antipsychotic agents, the investigators noted.

THC:CBD also led to a reduction in other symptoms associated with TS, particularly symptoms of OCD and anxiety.

The symptomatic response to THC:CBD correlated with serum metabolites of the cannabinoids, further supporting a biological relationship, the researchers noted.

There were no serious adverse events. Adverse effects with THC:CBD were generally mild. The most common adverse effect was cognitive difficulties, including slowed mentation, memory lapses, and poor concentration.

“Like many studies of psychoactive compounds, blinding among participants was a problem,” the researchers noted. Despite best efforts to conceal treatment allocation and match placebo to the active agent in terms of color and smell, most participants were able to correctly guess their treatment order.

Based on the findings in this small trial, larger and longer trials of THC:CBD in TS are warranted, they concluded.

“We need a plurality of treatment options in Tourette syndrome. For some, antipsychotics are effective tic-suppressing agents but for many these benefits are complicated by side effects such as weight gain & sedation,” Dr. Mosley tweeted. “Cannabinoids are a biologically plausible therapeutic agent. The body’s own ‘endocannabinoid’ receptors are concentrated in the basal ganglia – the neuroanatomical nexus of TS.”

The study was funded by the Wesley Medical Research Institute, Brisbane, and the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded research organization at the University of Sydney, Australia. Dr. Mosley reports no relevant financial relationships.
 

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

An oral oil containing tetrahydrocannabinol (THC) and cannabidiol (CBD) led to a significant and meaningful reduction in motor and vocal tics in patients with severe Tourette syndrome (TS), results of a double-blind, placebo-controlled, crossover study show.

“In a methodologically robust manner (and independent of any drug company sponsorship), we provide evidence for the effectiveness of repeated dosing with THC:CBD vs. placebo in tic suppression, as well as reduction of comorbid anxiety and obsessive-compulsive disorder in severe TS,” neuropsychiatrist and lead investigator Philip Mosley, PhD, said in an interview.

The results offer support to people with TS who “want to approach their doctor to try medicinal cannabis when other drugs have not worked or are intolerable,” said Dr. Mosley, of the Wesley Research Institute and QIMR Berghofer Medical Research Institute, Herston, Australia.

The study was published online in NEJM Evidence.
 

A viable treatment option

Twenty-two adults (mean age, 31 years) with severe TS received THC:CBD oil titrated upward over 6 weeks to a daily dose of 20 mg of THC and 20 mg of CBD, followed by a 6-week course of placebo (or vice versa). Six participants had not previously used cannabis.

The primary outcome was the total tic score on the Yale Global Tic Severity Scale (YGTSS; range 0 to 50 with higher scores = greater tic severity).

The mean baseline YGTSS total tic score was 35.7. At 6 weeks, the reduction in total tic score was 8.9 with THC:CBD vs. 2.5 with placebo.

A linear mixed-effects model (intention-to-treat) showed a significant interaction of treatment and visit number (P = .008), indicating a greater decrease (improvement) in tic score over time with THC:CBD, the study team reported.

On average, the magnitude of the tic reduction was “moderate” and comparable to the effect observed with existing treatments such as antipsychotic agents, the investigators noted.

THC:CBD also led to a reduction in other symptoms associated with TS, particularly symptoms of OCD and anxiety.

The symptomatic response to THC:CBD correlated with serum metabolites of the cannabinoids, further supporting a biological relationship, the researchers noted.

There were no serious adverse events. Adverse effects with THC:CBD were generally mild. The most common adverse effect was cognitive difficulties, including slowed mentation, memory lapses, and poor concentration.

“Like many studies of psychoactive compounds, blinding among participants was a problem,” the researchers noted. Despite best efforts to conceal treatment allocation and match placebo to the active agent in terms of color and smell, most participants were able to correctly guess their treatment order.

Based on the findings in this small trial, larger and longer trials of THC:CBD in TS are warranted, they concluded.

“We need a plurality of treatment options in Tourette syndrome. For some, antipsychotics are effective tic-suppressing agents but for many these benefits are complicated by side effects such as weight gain & sedation,” Dr. Mosley tweeted. “Cannabinoids are a biologically plausible therapeutic agent. The body’s own ‘endocannabinoid’ receptors are concentrated in the basal ganglia – the neuroanatomical nexus of TS.”

The study was funded by the Wesley Medical Research Institute, Brisbane, and the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded research organization at the University of Sydney, Australia. Dr. Mosley reports no relevant financial relationships.
 

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

An oral oil containing tetrahydrocannabinol (THC) and cannabidiol (CBD) led to a significant and meaningful reduction in motor and vocal tics in patients with severe Tourette syndrome (TS), results of a double-blind, placebo-controlled, crossover study show.

“In a methodologically robust manner (and independent of any drug company sponsorship), we provide evidence for the effectiveness of repeated dosing with THC:CBD vs. placebo in tic suppression, as well as reduction of comorbid anxiety and obsessive-compulsive disorder in severe TS,” neuropsychiatrist and lead investigator Philip Mosley, PhD, said in an interview.

The results offer support to people with TS who “want to approach their doctor to try medicinal cannabis when other drugs have not worked or are intolerable,” said Dr. Mosley, of the Wesley Research Institute and QIMR Berghofer Medical Research Institute, Herston, Australia.

The study was published online in NEJM Evidence.
 

A viable treatment option

Twenty-two adults (mean age, 31 years) with severe TS received THC:CBD oil titrated upward over 6 weeks to a daily dose of 20 mg of THC and 20 mg of CBD, followed by a 6-week course of placebo (or vice versa). Six participants had not previously used cannabis.

The primary outcome was the total tic score on the Yale Global Tic Severity Scale (YGTSS; range 0 to 50 with higher scores = greater tic severity).

The mean baseline YGTSS total tic score was 35.7. At 6 weeks, the reduction in total tic score was 8.9 with THC:CBD vs. 2.5 with placebo.

A linear mixed-effects model (intention-to-treat) showed a significant interaction of treatment and visit number (P = .008), indicating a greater decrease (improvement) in tic score over time with THC:CBD, the study team reported.

On average, the magnitude of the tic reduction was “moderate” and comparable to the effect observed with existing treatments such as antipsychotic agents, the investigators noted.

THC:CBD also led to a reduction in other symptoms associated with TS, particularly symptoms of OCD and anxiety.

The symptomatic response to THC:CBD correlated with serum metabolites of the cannabinoids, further supporting a biological relationship, the researchers noted.

There were no serious adverse events. Adverse effects with THC:CBD were generally mild. The most common adverse effect was cognitive difficulties, including slowed mentation, memory lapses, and poor concentration.

“Like many studies of psychoactive compounds, blinding among participants was a problem,” the researchers noted. Despite best efforts to conceal treatment allocation and match placebo to the active agent in terms of color and smell, most participants were able to correctly guess their treatment order.

Based on the findings in this small trial, larger and longer trials of THC:CBD in TS are warranted, they concluded.

“We need a plurality of treatment options in Tourette syndrome. For some, antipsychotics are effective tic-suppressing agents but for many these benefits are complicated by side effects such as weight gain & sedation,” Dr. Mosley tweeted. “Cannabinoids are a biologically plausible therapeutic agent. The body’s own ‘endocannabinoid’ receptors are concentrated in the basal ganglia – the neuroanatomical nexus of TS.”

The study was funded by the Wesley Medical Research Institute, Brisbane, and the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded research organization at the University of Sydney, Australia. Dr. Mosley reports no relevant financial relationships.
 

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

Key clinical point: Compared with whole breast irradiation (WBI), partial breast irradiation (PBI) led to a similar rate of ipsilateral breast recurrences (IBR) and demonstrated a better toxicity profile in patients with early-stage breast cancer (BC).

Major finding: Rate of IBR was comparable with PBI vs WBI at 5 years (relative risk [RR] 1.34; 95% CI 0.83-2.18) and 10 years (RR 1.29; 95% CI 0.87-1.91). Patients undergoing PBI vs WBI reported fewer acute adverse events (AE; incidence rate ratio [IRR] 0.53; 95% CI 0.31-0.92) and acute grade ≥2 AE (IRR 0.21; 95% CI 0.07-0.62).

Study details: Findings are from a meta-analysis of 14 randomized controlled trials and six comparative observational studies comparing any PBI modality with WBI in 17,234 adults with early-stage BC.

Disclosures: This study was supported by the US Agency for Healthcare Research and Quality. The authors declared no conflicts of interest.

Source: Shumway DA et al. Partial breast irradiation compared with whole breast irradiation: A systematic review and meta-analysis. J Natl Cancer Inst. 2023 (Jun 8). doi: 10.1093/jnci/djad100

Key clinical point: Compared with whole breast irradiation (WBI), partial breast irradiation (PBI) led to a similar rate of ipsilateral breast recurrences (IBR) and demonstrated a better toxicity profile in patients with early-stage breast cancer (BC).

Major finding: Rate of IBR was comparable with PBI vs WBI at 5 years (relative risk [RR] 1.34; 95% CI 0.83-2.18) and 10 years (RR 1.29; 95% CI 0.87-1.91). Patients undergoing PBI vs WBI reported fewer acute adverse events (AE; incidence rate ratio [IRR] 0.53; 95% CI 0.31-0.92) and acute grade ≥2 AE (IRR 0.21; 95% CI 0.07-0.62).

Study details: Findings are from a meta-analysis of 14 randomized controlled trials and six comparative observational studies comparing any PBI modality with WBI in 17,234 adults with early-stage BC.

Disclosures: This study was supported by the US Agency for Healthcare Research and Quality. The authors declared no conflicts of interest.

Source: Shumway DA et al. Partial breast irradiation compared with whole breast irradiation: A systematic review and meta-analysis. J Natl Cancer Inst. 2023 (Jun 8). doi: 10.1093/jnci/djad100

Key clinical point: Compared with whole breast irradiation (WBI), partial breast irradiation (PBI) led to a similar rate of ipsilateral breast recurrences (IBR) and demonstrated a better toxicity profile in patients with early-stage breast cancer (BC).

Major finding: Rate of IBR was comparable with PBI vs WBI at 5 years (relative risk [RR] 1.34; 95% CI 0.83-2.18) and 10 years (RR 1.29; 95% CI 0.87-1.91). Patients undergoing PBI vs WBI reported fewer acute adverse events (AE; incidence rate ratio [IRR] 0.53; 95% CI 0.31-0.92) and acute grade ≥2 AE (IRR 0.21; 95% CI 0.07-0.62).

Study details: Findings are from a meta-analysis of 14 randomized controlled trials and six comparative observational studies comparing any PBI modality with WBI in 17,234 adults with early-stage BC.

Disclosures: This study was supported by the US Agency for Healthcare Research and Quality. The authors declared no conflicts of interest.

Source: Shumway DA et al. Partial breast irradiation compared with whole breast irradiation: A systematic review and meta-analysis. J Natl Cancer Inst. 2023 (Jun 8). doi: 10.1093/jnci/djad100

Key clinical point: Targeted axillary dissection (TAD) after neoadjuvant systemic therapy was oncologically safe and led to excellent clinical outcomes in patients with node-positive early breast cancer (BC) who did not undergo axillary lymph node dissection (ALND).

Major finding: TAD alone vs TAD plus ALND was not associated with a higher risk for invasive disease-free survival (adjusted hazard ratio [aHR] 0.83; P = .69) and overall survival (aHR 1.07; P = .91).

Study details: Findings are from a cohort study including 199 patients with clinical stage T1-T4, node-positive early BC without distant metastases who underwent TAD with (40.2%) or without (59.8%) further axillary surgery.

Disclosures: The clips used to mark the targeted lymph nodes were provided for free by Tumark Vision (SOMATEX) and O-Twist (BIP). The authors declared receiving personal fees, honoraria, research funding, or other nonfinancial supports from various sources.

Source: Kuemmel S et al. Safety of targeted axillary dissection after neoadjuvant therapy in patients with node-positive breast cancer. JAMA Surg. 2023 (Jun 7). doi: 10.1001/jamasurg.2023.1772

Key clinical point: Targeted axillary dissection (TAD) after neoadjuvant systemic therapy was oncologically safe and led to excellent clinical outcomes in patients with node-positive early breast cancer (BC) who did not undergo axillary lymph node dissection (ALND).

Major finding: TAD alone vs TAD plus ALND was not associated with a higher risk for invasive disease-free survival (adjusted hazard ratio [aHR] 0.83; P = .69) and overall survival (aHR 1.07; P = .91).

Study details: Findings are from a cohort study including 199 patients with clinical stage T1-T4, node-positive early BC without distant metastases who underwent TAD with (40.2%) or without (59.8%) further axillary surgery.

Disclosures: The clips used to mark the targeted lymph nodes were provided for free by Tumark Vision (SOMATEX) and O-Twist (BIP). The authors declared receiving personal fees, honoraria, research funding, or other nonfinancial supports from various sources.

Source: Kuemmel S et al. Safety of targeted axillary dissection after neoadjuvant therapy in patients with node-positive breast cancer. JAMA Surg. 2023 (Jun 7). doi: 10.1001/jamasurg.2023.1772

Key clinical point: Targeted axillary dissection (TAD) after neoadjuvant systemic therapy was oncologically safe and led to excellent clinical outcomes in patients with node-positive early breast cancer (BC) who did not undergo axillary lymph node dissection (ALND).

Major finding: TAD alone vs TAD plus ALND was not associated with a higher risk for invasive disease-free survival (adjusted hazard ratio [aHR] 0.83; P = .69) and overall survival (aHR 1.07; P = .91).

Study details: Findings are from a cohort study including 199 patients with clinical stage T1-T4, node-positive early BC without distant metastases who underwent TAD with (40.2%) or without (59.8%) further axillary surgery.

Disclosures: The clips used to mark the targeted lymph nodes were provided for free by Tumark Vision (SOMATEX) and O-Twist (BIP). The authors declared receiving personal fees, honoraria, research funding, or other nonfinancial supports from various sources.

Source: Kuemmel S et al. Safety of targeted axillary dissection after neoadjuvant therapy in patients with node-positive breast cancer. JAMA Surg. 2023 (Jun 7). doi: 10.1001/jamasurg.2023.1772

Key clinical point: In addition to switching endocrine therapy (ET), continuing the cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with ribociclib therapy vs placebo demonstrated progression-free survival (PFS) benefits in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (BC) who had progressed on previous ET and CDK4/6i.

Major finding: At a median follow-up of 18.2 months, a significant improvement in PFS was observed in the ET+ribociclib+CDK4/6i vs ET+placebo group (hazard ratio 0.57; P = .006). ET+ribociclib+CDK4/6i demonstrated a manageable safety profile.

Study details: Findings are from the phase 2 MAINTAIN trial including 119 patients with HR+/HER2− metastatic BC who progressed on ET and CDK4/6i and were randomly assigned to receive a different ET with ribociclib plus CDK4/6i or placebo.

Disclosures: This study was supported by Novartis Pharmaceuticals and other sources. The authors declared no conflicts of interest.

Source: Kalinsky K et al. Randomized phase II trial of endocrine therapy with or without ribociclib after progression on cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: MAINTAIN trial. J Clin Oncol. 2023 (May 19). doi: 10.1200/JCO.22.02392

Key clinical point: In addition to switching endocrine therapy (ET), continuing the cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with ribociclib therapy vs placebo demonstrated progression-free survival (PFS) benefits in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (BC) who had progressed on previous ET and CDK4/6i.

Major finding: At a median follow-up of 18.2 months, a significant improvement in PFS was observed in the ET+ribociclib+CDK4/6i vs ET+placebo group (hazard ratio 0.57; P = .006). ET+ribociclib+CDK4/6i demonstrated a manageable safety profile.

Study details: Findings are from the phase 2 MAINTAIN trial including 119 patients with HR+/HER2− metastatic BC who progressed on ET and CDK4/6i and were randomly assigned to receive a different ET with ribociclib plus CDK4/6i or placebo.

Disclosures: This study was supported by Novartis Pharmaceuticals and other sources. The authors declared no conflicts of interest.

Source: Kalinsky K et al. Randomized phase II trial of endocrine therapy with or without ribociclib after progression on cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: MAINTAIN trial. J Clin Oncol. 2023 (May 19). doi: 10.1200/JCO.22.02392

Key clinical point: In addition to switching endocrine therapy (ET), continuing the cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with ribociclib therapy vs placebo demonstrated progression-free survival (PFS) benefits in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (BC) who had progressed on previous ET and CDK4/6i.

Major finding: At a median follow-up of 18.2 months, a significant improvement in PFS was observed in the ET+ribociclib+CDK4/6i vs ET+placebo group (hazard ratio 0.57; P = .006). ET+ribociclib+CDK4/6i demonstrated a manageable safety profile.

Study details: Findings are from the phase 2 MAINTAIN trial including 119 patients with HR+/HER2− metastatic BC who progressed on ET and CDK4/6i and were randomly assigned to receive a different ET with ribociclib plus CDK4/6i or placebo.

Disclosures: This study was supported by Novartis Pharmaceuticals and other sources. The authors declared no conflicts of interest.

Source: Kalinsky K et al. Randomized phase II trial of endocrine therapy with or without ribociclib after progression on cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: MAINTAIN trial. J Clin Oncol. 2023 (May 19). doi: 10.1200/JCO.22.02392

Key clinical point: Dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor, plus letrozole or anastrozole demonstrated progression-free survival (PFS) benefits and a manageable safety profile in untreated patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: A 12.4-month improvement in PFS was observed with dalpiciclib vs placebo, with both letrozole and anastrozole (stratified hazard ratio 0.51; P < .0001). Dalpiciclib plus letrozole or anastrozole demonstrated a manageable safety profile, with similar proportions of patients in the dalpiciclib and placebo groups (4% and 2%, respectively) discontinuing the treatment.

Study details: Findings are from the phase 3 DAWNA-2 study including 456 patients with HR+/HER2− advanced BC who were randomly assigned to receive either letrozole or anastrozole with dalpiciclib or placebo.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals and partly by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. Three authors declared being employees of Hengrui, and Binghe Xu declared receiving research grants and fees from some sources.

Source: Zhang P et al. Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023;24:646-657 (May 11). doi: 10.1016/S1470-2045(23)00172-9

Key clinical point: Dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor, plus letrozole or anastrozole demonstrated progression-free survival (PFS) benefits and a manageable safety profile in untreated patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: A 12.4-month improvement in PFS was observed with dalpiciclib vs placebo, with both letrozole and anastrozole (stratified hazard ratio 0.51; P < .0001). Dalpiciclib plus letrozole or anastrozole demonstrated a manageable safety profile, with similar proportions of patients in the dalpiciclib and placebo groups (4% and 2%, respectively) discontinuing the treatment.

Study details: Findings are from the phase 3 DAWNA-2 study including 456 patients with HR+/HER2− advanced BC who were randomly assigned to receive either letrozole or anastrozole with dalpiciclib or placebo.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals and partly by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. Three authors declared being employees of Hengrui, and Binghe Xu declared receiving research grants and fees from some sources.

Source: Zhang P et al. Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023;24:646-657 (May 11). doi: 10.1016/S1470-2045(23)00172-9

Key clinical point: Dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor, plus letrozole or anastrozole demonstrated progression-free survival (PFS) benefits and a manageable safety profile in untreated patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: A 12.4-month improvement in PFS was observed with dalpiciclib vs placebo, with both letrozole and anastrozole (stratified hazard ratio 0.51; P < .0001). Dalpiciclib plus letrozole or anastrozole demonstrated a manageable safety profile, with similar proportions of patients in the dalpiciclib and placebo groups (4% and 2%, respectively) discontinuing the treatment.

Study details: Findings are from the phase 3 DAWNA-2 study including 456 patients with HR+/HER2− advanced BC who were randomly assigned to receive either letrozole or anastrozole with dalpiciclib or placebo.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals and partly by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. Three authors declared being employees of Hengrui, and Binghe Xu declared receiving research grants and fees from some sources.

Source: Zhang P et al. Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023;24:646-657 (May 11). doi: 10.1016/S1470-2045(23)00172-9

Key clinical point: The combination of apatinib and etoposide proved to be a feasible treatment option for patients with triple-negative breast cancer (TNBC) who had failed ≥1 line of chemotherapy in the advanced setting.

Major finding: The median progression-free survival and overall survival were 6.0 and 24.5 months, respectively, with an objective response rate of 10.0% and a disease control rate of 62.5%. Overall, 95.0% of patients experienced adverse events (AE) of any grade, mostly grade 1 and 2. Hypertension (65.0%), nausea (47.5%), vomiting (42.5%), and hand-foot syndrome (32.5%) were the most common AE.

Study details: Findings are from a single-arm phase 2 study including 40 patients with advanced TNBC who had failed ≥1 line of chemotherapy and received oral apatinib plus oral etoposide.

Disclosures: This study was funded by National Cancer Fund Climbing Fund. The authors declared no conflicts of interest.

Source: Cao M et al. Apatinib plus etoposide in pretreated patients with advanced triple-negative breast cancer: A phase II trial. BMC Cancer. 2023;23:463 (May 19). doi: 10.1186/s12885-023-10768-8

Key clinical point: The combination of apatinib and etoposide proved to be a feasible treatment option for patients with triple-negative breast cancer (TNBC) who had failed ≥1 line of chemotherapy in the advanced setting.

Major finding: The median progression-free survival and overall survival were 6.0 and 24.5 months, respectively, with an objective response rate of 10.0% and a disease control rate of 62.5%. Overall, 95.0% of patients experienced adverse events (AE) of any grade, mostly grade 1 and 2. Hypertension (65.0%), nausea (47.5%), vomiting (42.5%), and hand-foot syndrome (32.5%) were the most common AE.

Study details: Findings are from a single-arm phase 2 study including 40 patients with advanced TNBC who had failed ≥1 line of chemotherapy and received oral apatinib plus oral etoposide.

Disclosures: This study was funded by National Cancer Fund Climbing Fund. The authors declared no conflicts of interest.

Source: Cao M et al. Apatinib plus etoposide in pretreated patients with advanced triple-negative breast cancer: A phase II trial. BMC Cancer. 2023;23:463 (May 19). doi: 10.1186/s12885-023-10768-8

Key clinical point: The combination of apatinib and etoposide proved to be a feasible treatment option for patients with triple-negative breast cancer (TNBC) who had failed ≥1 line of chemotherapy in the advanced setting.

Major finding: The median progression-free survival and overall survival were 6.0 and 24.5 months, respectively, with an objective response rate of 10.0% and a disease control rate of 62.5%. Overall, 95.0% of patients experienced adverse events (AE) of any grade, mostly grade 1 and 2. Hypertension (65.0%), nausea (47.5%), vomiting (42.5%), and hand-foot syndrome (32.5%) were the most common AE.

Study details: Findings are from a single-arm phase 2 study including 40 patients with advanced TNBC who had failed ≥1 line of chemotherapy and received oral apatinib plus oral etoposide.

Disclosures: This study was funded by National Cancer Fund Climbing Fund. The authors declared no conflicts of interest.

Source: Cao M et al. Apatinib plus etoposide in pretreated patients with advanced triple-negative breast cancer: A phase II trial. BMC Cancer. 2023;23:463 (May 19). doi: 10.1186/s12885-023-10768-8

A panel of advisers to the Food and Drug Administration unanimously has agreed that the next COVID-19 vaccines should target the XBB variants of the SARS-CoV-2 virus now in circulation in the United States, but questioned whether the population as a whole needs booster shots and how often they should be given.

The Vaccines and Related Biological Products Advisory Committee of the FDA voted 21-0 in favor of the recommendation about the strain to be used in the next crop of vaccines.

In the briefing document for the meeting, FDA staff said the available evidence suggests that a monovalent (single-strain) XBB-lineage vaccine “is warranted” for the 2023-2024 vaccination campaign and would replace the current bivalent vaccine, which targets the original version of the virus and two strains from the Omicron variant.

FDA staff also noted how such a shift would be in line with the World Health Organization toward targeting the XBB family of subvariants. European regulators have done this as well. 

The FDA is not obligated to act on the panel’s recommendations. But the agency often does and is highly likely to do so in this case. Vaccine companies will need the recommendation from the FDA to begin making vaccines for the fall.
 

New shot every year?

The FDA asked its expert panel to vote only on the question about the makeup of future vaccines in terms of which strain to include. 

But panelists also raised other questions during the meeting, including concerns about moves toward tying COVID vaccinations into the model of annual flu shots. 

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, argued for greater focus on the response of T cells after vaccination, even in light of the already recognized waning of antibody protection. 

In a recent Substack article, Dr. Offit called T cells the “unsung hero” of the pandemic. They take longer to develop after infection or vaccination than the antibodies that first attack the virus, but immune memory cells called B and T cells “are long-lived,” and their “protection against severe disease often lasts for years and sometimes decades.”

Dr. Offit said he was concerned about using a blanket approach for future recommendations for COVID vaccinations, following the one now in place for influenza vaccines.

The Centers for Disease Control and Prevention recommends flu shots for everyone 6 months and older, with rare exceptions. 

“We need to continue to define who those high-risk groups are and not make this a recommendation for everybody every season,” he said.

Dr. Offit offered his own experience as an example. While he had been vaccinated against the virus’s early Wuhan strain, he still was infected, most likely with a variant that emerged later. 

“That was a drifted virus. That’s why I had a mild infection but I didn’t have a severe infection, because presumably I had T cells which prevented that severe infection, which may last for years,” Dr. Offit said.

Pfizer and Moderna, the two companies that make mRNA-based COVID vaccines, are working on experimental products meant to protect against both flu and SARS-COv-2 in one shot. Novavax, maker of a more traditional protein-based COVID shot, is doing the same. 

The idea of these combination products is to make it more convenient for people to protect against both viruses, while also offering companies some marketing advantages.

But without referring to these drugmakers’ plans for future combo flu-COVID shots, members of the FDA panel raised objections to an assumption of routine annual vaccines against variants of SARS-CoV-2. 

Among the panelists who expressed concerns was Henry H. Bernstein, DO, a former member of the CDC’s Advisory Committee on Immunization Practices. 

Bernstein questioned the approach of dubbing these the “2023-2024 formulas,” as this approach conveyed a sense of an expectation for a need for annual vaccines, as happens with flu. 

“It’s not clear to me that this is a seasonal virus yet,” said Dr. Bernstein, who is also a professor of pediatrics at Hofstra University, Hempstead, N.Y..

In response to Dr. Bernstein’s point, Arnold Monto, MD, the acting chair of the FDA panel, suggested such a pattern could emerge, while also agreeing that it’s too soon to say for sure.

A professor emeritus at the University of Michigan, Ann Arbor, Dr. Monto’s career included pandemic planning and emergency response to virus outbreaks, including the 1968 Hong Kong influenza pandemic, avian influenza, and the original SARS.

“I think it’s premature to say that this virus will not become seasonal,” Dr. Monto said about SARS-CoV-2. “I agree. We’re not there yet, but we may be.”

At the end of the meeting, Dr. Monto recapped the meeting’s key points, noting that there was a general consensus that the XBB.1.5 subvariant would be the best to use in future COVID shots. 

He also noted that Novavax, which makes the more traditional protein-based vaccine, along with Pfizer and Moderna, already have honed in on this subvariant, which would allow for rapid development of updated COVID vaccines.

“The fact that most of the manufacturers are ready to work on an XBB 1.5 [vaccine] is an added reason to select this strain or this variant, given the immunologic data,” Dr. Monto said. 

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said the demands involved in manufacturing vaccines tilts toward annual changes.

“Practically, we’re going to have one update per year, barring a heroic effort to deal with a strain that pops up that is essentially so different that it requires us to mobilize tremendous resources to address that strain change,” he said.

Dr. Marks questioned the panelists’ concerns about likening flu and COVID vaccination practices. The FDA staff’s intent was to try to help the public understand the need for follow-on vaccination.

“I’m really having trouble understanding that committee’s need to bristle against something that’s similar to influenza. People understand a yearly influenza vaccine,” Dr. Marks said. 

And it’s not certain when another major change in the COVID virus will follow the XBB subvariant, but it’s likely one will – and soon, Dr. Marks said. 

“It looks like, probably by next fall, there’ll be further drift from this,” he said.
 

Informing the public 

Dr. Marks also stressed the need to better convey the benefits of vaccination to people in the United States. 

CDC data estimate that 70% of the U.S. population completed an initial series of the original monovalent vaccines, with only 17% then getting bivalent shots. There’s even a decline among people ages 65 and older. CDC estimates 94% of this group completed their primary series, but only 43% got the bivalent booster dose.

“We have to do better because we have not done a good job today communicating to the American public what’s going on here,” Marks said.

Researchers also are still trying to determine the best timing for people to get additional COVID shots. Finding the “sweet spot” where people can maximize additional protection is tricky, with people most protected if they happen to get shot near the beginning of an uptick in viral spread, the CDC’s Ruth Link-Gelles, PhD, MPH, told the panel during a presentation. 

“You’re going to get the best incremental benefit if it’s been longer since your last vaccine,” she said. “But of course, if you wait too long since your last vaccine, you’re left with very little protection, and so you’re at higher risk of severe illness.”

Like Dr. Marks, Dr. Link-Gelles stressed the need for persuading more people to get follow-on vaccines. 

“Most Americans, at this point, haven’t even received the bivalent and so are a year or more out from their monovalent dose and so have relatively little protection left,” she said.

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

A panel of advisers to the Food and Drug Administration unanimously has agreed that the next COVID-19 vaccines should target the XBB variants of the SARS-CoV-2 virus now in circulation in the United States, but questioned whether the population as a whole needs booster shots and how often they should be given.

The Vaccines and Related Biological Products Advisory Committee of the FDA voted 21-0 in favor of the recommendation about the strain to be used in the next crop of vaccines.

In the briefing document for the meeting, FDA staff said the available evidence suggests that a monovalent (single-strain) XBB-lineage vaccine “is warranted” for the 2023-2024 vaccination campaign and would replace the current bivalent vaccine, which targets the original version of the virus and two strains from the Omicron variant.

FDA staff also noted how such a shift would be in line with the World Health Organization toward targeting the XBB family of subvariants. European regulators have done this as well. 

The FDA is not obligated to act on the panel’s recommendations. But the agency often does and is highly likely to do so in this case. Vaccine companies will need the recommendation from the FDA to begin making vaccines for the fall.
 

New shot every year?

The FDA asked its expert panel to vote only on the question about the makeup of future vaccines in terms of which strain to include. 

But panelists also raised other questions during the meeting, including concerns about moves toward tying COVID vaccinations into the model of annual flu shots. 

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, argued for greater focus on the response of T cells after vaccination, even in light of the already recognized waning of antibody protection. 

In a recent Substack article, Dr. Offit called T cells the “unsung hero” of the pandemic. They take longer to develop after infection or vaccination than the antibodies that first attack the virus, but immune memory cells called B and T cells “are long-lived,” and their “protection against severe disease often lasts for years and sometimes decades.”

Dr. Offit said he was concerned about using a blanket approach for future recommendations for COVID vaccinations, following the one now in place for influenza vaccines.

The Centers for Disease Control and Prevention recommends flu shots for everyone 6 months and older, with rare exceptions. 

“We need to continue to define who those high-risk groups are and not make this a recommendation for everybody every season,” he said.

Dr. Offit offered his own experience as an example. While he had been vaccinated against the virus’s early Wuhan strain, he still was infected, most likely with a variant that emerged later. 

“That was a drifted virus. That’s why I had a mild infection but I didn’t have a severe infection, because presumably I had T cells which prevented that severe infection, which may last for years,” Dr. Offit said.

Pfizer and Moderna, the two companies that make mRNA-based COVID vaccines, are working on experimental products meant to protect against both flu and SARS-COv-2 in one shot. Novavax, maker of a more traditional protein-based COVID shot, is doing the same. 

The idea of these combination products is to make it more convenient for people to protect against both viruses, while also offering companies some marketing advantages.

But without referring to these drugmakers’ plans for future combo flu-COVID shots, members of the FDA panel raised objections to an assumption of routine annual vaccines against variants of SARS-CoV-2. 

Among the panelists who expressed concerns was Henry H. Bernstein, DO, a former member of the CDC’s Advisory Committee on Immunization Practices. 

Bernstein questioned the approach of dubbing these the “2023-2024 formulas,” as this approach conveyed a sense of an expectation for a need for annual vaccines, as happens with flu. 

“It’s not clear to me that this is a seasonal virus yet,” said Dr. Bernstein, who is also a professor of pediatrics at Hofstra University, Hempstead, N.Y..

In response to Dr. Bernstein’s point, Arnold Monto, MD, the acting chair of the FDA panel, suggested such a pattern could emerge, while also agreeing that it’s too soon to say for sure.

A professor emeritus at the University of Michigan, Ann Arbor, Dr. Monto’s career included pandemic planning and emergency response to virus outbreaks, including the 1968 Hong Kong influenza pandemic, avian influenza, and the original SARS.

“I think it’s premature to say that this virus will not become seasonal,” Dr. Monto said about SARS-CoV-2. “I agree. We’re not there yet, but we may be.”

At the end of the meeting, Dr. Monto recapped the meeting’s key points, noting that there was a general consensus that the XBB.1.5 subvariant would be the best to use in future COVID shots. 

He also noted that Novavax, which makes the more traditional protein-based vaccine, along with Pfizer and Moderna, already have honed in on this subvariant, which would allow for rapid development of updated COVID vaccines.

“The fact that most of the manufacturers are ready to work on an XBB 1.5 [vaccine] is an added reason to select this strain or this variant, given the immunologic data,” Dr. Monto said. 

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said the demands involved in manufacturing vaccines tilts toward annual changes.

“Practically, we’re going to have one update per year, barring a heroic effort to deal with a strain that pops up that is essentially so different that it requires us to mobilize tremendous resources to address that strain change,” he said.

Dr. Marks questioned the panelists’ concerns about likening flu and COVID vaccination practices. The FDA staff’s intent was to try to help the public understand the need for follow-on vaccination.

“I’m really having trouble understanding that committee’s need to bristle against something that’s similar to influenza. People understand a yearly influenza vaccine,” Dr. Marks said. 

And it’s not certain when another major change in the COVID virus will follow the XBB subvariant, but it’s likely one will – and soon, Dr. Marks said. 

“It looks like, probably by next fall, there’ll be further drift from this,” he said.
 

Informing the public 

Dr. Marks also stressed the need to better convey the benefits of vaccination to people in the United States. 

CDC data estimate that 70% of the U.S. population completed an initial series of the original monovalent vaccines, with only 17% then getting bivalent shots. There’s even a decline among people ages 65 and older. CDC estimates 94% of this group completed their primary series, but only 43% got the bivalent booster dose.

“We have to do better because we have not done a good job today communicating to the American public what’s going on here,” Marks said.

Researchers also are still trying to determine the best timing for people to get additional COVID shots. Finding the “sweet spot” where people can maximize additional protection is tricky, with people most protected if they happen to get shot near the beginning of an uptick in viral spread, the CDC’s Ruth Link-Gelles, PhD, MPH, told the panel during a presentation. 

“You’re going to get the best incremental benefit if it’s been longer since your last vaccine,” she said. “But of course, if you wait too long since your last vaccine, you’re left with very little protection, and so you’re at higher risk of severe illness.”

Like Dr. Marks, Dr. Link-Gelles stressed the need for persuading more people to get follow-on vaccines. 

“Most Americans, at this point, haven’t even received the bivalent and so are a year or more out from their monovalent dose and so have relatively little protection left,” she said.

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

A panel of advisers to the Food and Drug Administration unanimously has agreed that the next COVID-19 vaccines should target the XBB variants of the SARS-CoV-2 virus now in circulation in the United States, but questioned whether the population as a whole needs booster shots and how often they should be given.

The Vaccines and Related Biological Products Advisory Committee of the FDA voted 21-0 in favor of the recommendation about the strain to be used in the next crop of vaccines.

In the briefing document for the meeting, FDA staff said the available evidence suggests that a monovalent (single-strain) XBB-lineage vaccine “is warranted” for the 2023-2024 vaccination campaign and would replace the current bivalent vaccine, which targets the original version of the virus and two strains from the Omicron variant.

FDA staff also noted how such a shift would be in line with the World Health Organization toward targeting the XBB family of subvariants. European regulators have done this as well. 

The FDA is not obligated to act on the panel’s recommendations. But the agency often does and is highly likely to do so in this case. Vaccine companies will need the recommendation from the FDA to begin making vaccines for the fall.
 

New shot every year?

The FDA asked its expert panel to vote only on the question about the makeup of future vaccines in terms of which strain to include. 

But panelists also raised other questions during the meeting, including concerns about moves toward tying COVID vaccinations into the model of annual flu shots. 

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, argued for greater focus on the response of T cells after vaccination, even in light of the already recognized waning of antibody protection. 

In a recent Substack article, Dr. Offit called T cells the “unsung hero” of the pandemic. They take longer to develop after infection or vaccination than the antibodies that first attack the virus, but immune memory cells called B and T cells “are long-lived,” and their “protection against severe disease often lasts for years and sometimes decades.”

Dr. Offit said he was concerned about using a blanket approach for future recommendations for COVID vaccinations, following the one now in place for influenza vaccines.

The Centers for Disease Control and Prevention recommends flu shots for everyone 6 months and older, with rare exceptions. 

“We need to continue to define who those high-risk groups are and not make this a recommendation for everybody every season,” he said.

Dr. Offit offered his own experience as an example. While he had been vaccinated against the virus’s early Wuhan strain, he still was infected, most likely with a variant that emerged later. 

“That was a drifted virus. That’s why I had a mild infection but I didn’t have a severe infection, because presumably I had T cells which prevented that severe infection, which may last for years,” Dr. Offit said.

Pfizer and Moderna, the two companies that make mRNA-based COVID vaccines, are working on experimental products meant to protect against both flu and SARS-COv-2 in one shot. Novavax, maker of a more traditional protein-based COVID shot, is doing the same. 

The idea of these combination products is to make it more convenient for people to protect against both viruses, while also offering companies some marketing advantages.

But without referring to these drugmakers’ plans for future combo flu-COVID shots, members of the FDA panel raised objections to an assumption of routine annual vaccines against variants of SARS-CoV-2. 

Among the panelists who expressed concerns was Henry H. Bernstein, DO, a former member of the CDC’s Advisory Committee on Immunization Practices. 

Bernstein questioned the approach of dubbing these the “2023-2024 formulas,” as this approach conveyed a sense of an expectation for a need for annual vaccines, as happens with flu. 

“It’s not clear to me that this is a seasonal virus yet,” said Dr. Bernstein, who is also a professor of pediatrics at Hofstra University, Hempstead, N.Y..

In response to Dr. Bernstein’s point, Arnold Monto, MD, the acting chair of the FDA panel, suggested such a pattern could emerge, while also agreeing that it’s too soon to say for sure.

A professor emeritus at the University of Michigan, Ann Arbor, Dr. Monto’s career included pandemic planning and emergency response to virus outbreaks, including the 1968 Hong Kong influenza pandemic, avian influenza, and the original SARS.

“I think it’s premature to say that this virus will not become seasonal,” Dr. Monto said about SARS-CoV-2. “I agree. We’re not there yet, but we may be.”

At the end of the meeting, Dr. Monto recapped the meeting’s key points, noting that there was a general consensus that the XBB.1.5 subvariant would be the best to use in future COVID shots. 

He also noted that Novavax, which makes the more traditional protein-based vaccine, along with Pfizer and Moderna, already have honed in on this subvariant, which would allow for rapid development of updated COVID vaccines.

“The fact that most of the manufacturers are ready to work on an XBB 1.5 [vaccine] is an added reason to select this strain or this variant, given the immunologic data,” Dr. Monto said. 

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said the demands involved in manufacturing vaccines tilts toward annual changes.

“Practically, we’re going to have one update per year, barring a heroic effort to deal with a strain that pops up that is essentially so different that it requires us to mobilize tremendous resources to address that strain change,” he said.

Dr. Marks questioned the panelists’ concerns about likening flu and COVID vaccination practices. The FDA staff’s intent was to try to help the public understand the need for follow-on vaccination.

“I’m really having trouble understanding that committee’s need to bristle against something that’s similar to influenza. People understand a yearly influenza vaccine,” Dr. Marks said. 

And it’s not certain when another major change in the COVID virus will follow the XBB subvariant, but it’s likely one will – and soon, Dr. Marks said. 

“It looks like, probably by next fall, there’ll be further drift from this,” he said.
 

Informing the public 

Dr. Marks also stressed the need to better convey the benefits of vaccination to people in the United States. 

CDC data estimate that 70% of the U.S. population completed an initial series of the original monovalent vaccines, with only 17% then getting bivalent shots. There’s even a decline among people ages 65 and older. CDC estimates 94% of this group completed their primary series, but only 43% got the bivalent booster dose.

“We have to do better because we have not done a good job today communicating to the American public what’s going on here,” Marks said.

Researchers also are still trying to determine the best timing for people to get additional COVID shots. Finding the “sweet spot” where people can maximize additional protection is tricky, with people most protected if they happen to get shot near the beginning of an uptick in viral spread, the CDC’s Ruth Link-Gelles, PhD, MPH, told the panel during a presentation. 

“You’re going to get the best incremental benefit if it’s been longer since your last vaccine,” she said. “But of course, if you wait too long since your last vaccine, you’re left with very little protection, and so you’re at higher risk of severe illness.”

Like Dr. Marks, Dr. Link-Gelles stressed the need for persuading more people to get follow-on vaccines. 

“Most Americans, at this point, haven’t even received the bivalent and so are a year or more out from their monovalent dose and so have relatively little protection left,” she said.

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

Key clinical point: Atypical hyperplasia (AH) at the surgical margins of breast-conserving surgery (BCS) did not increase the risk for ipsilateral breast cancer (BC) recurrence, distant metastasis, or mortality in patients with BC who had received neoadjuvant chemotherapy (NAC).

Major finding: The 5-year ipsilateral breast tumor recurrence (IBTR) rate was 4.6% (95% CI 3.2%-6.0%) in patients with AH and 6.2% (95% CI 4.6%-7.8%) in patients without AH, with no significant differences observed between both groups in terms of IBTR (P = .448), distant metastasis-free survival (P = .506), and overall survival (P = .432).

Study details: Findings are from a retrospective analysis including 598 patients with BC who received NAC and BCS, of which 301 patients had AH at the margins of BCS and 297 patients did not have AH at the margins of BCS.

Disclosures: This study was supported by grants from the Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Su A et al. Impact of atypical hyperplasia at surgical margins on breast cancer outcomes in patients treated with neoadjuvant chemotherapy. Front Oncol. 2023;13:1202689 (May 19). Doi: 10.3389/fonc.2023.1202689

Key clinical point: Atypical hyperplasia (AH) at the surgical margins of breast-conserving surgery (BCS) did not increase the risk for ipsilateral breast cancer (BC) recurrence, distant metastasis, or mortality in patients with BC who had received neoadjuvant chemotherapy (NAC).

Major finding: The 5-year ipsilateral breast tumor recurrence (IBTR) rate was 4.6% (95% CI 3.2%-6.0%) in patients with AH and 6.2% (95% CI 4.6%-7.8%) in patients without AH, with no significant differences observed between both groups in terms of IBTR (P = .448), distant metastasis-free survival (P = .506), and overall survival (P = .432).

Study details: Findings are from a retrospective analysis including 598 patients with BC who received NAC and BCS, of which 301 patients had AH at the margins of BCS and 297 patients did not have AH at the margins of BCS.

Disclosures: This study was supported by grants from the Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Su A et al. Impact of atypical hyperplasia at surgical margins on breast cancer outcomes in patients treated with neoadjuvant chemotherapy. Front Oncol. 2023;13:1202689 (May 19). Doi: 10.3389/fonc.2023.1202689

Key clinical point: Atypical hyperplasia (AH) at the surgical margins of breast-conserving surgery (BCS) did not increase the risk for ipsilateral breast cancer (BC) recurrence, distant metastasis, or mortality in patients with BC who had received neoadjuvant chemotherapy (NAC).

Major finding: The 5-year ipsilateral breast tumor recurrence (IBTR) rate was 4.6% (95% CI 3.2%-6.0%) in patients with AH and 6.2% (95% CI 4.6%-7.8%) in patients without AH, with no significant differences observed between both groups in terms of IBTR (P = .448), distant metastasis-free survival (P = .506), and overall survival (P = .432).

Study details: Findings are from a retrospective analysis including 598 patients with BC who received NAC and BCS, of which 301 patients had AH at the margins of BCS and 297 patients did not have AH at the margins of BCS.

Disclosures: This study was supported by grants from the Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Su A et al. Impact of atypical hyperplasia at surgical margins on breast cancer outcomes in patients treated with neoadjuvant chemotherapy. Front Oncol. 2023;13:1202689 (May 19). Doi: 10.3389/fonc.2023.1202689