Breast Cancer ICYMI

Key clinical point: Low vs no human epidermal growth factor receptor 2 (ERBB2, aka HER2) expression had no impact on survival outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (BC) who were treated with targeted therapy (TT) plus endocrine therapy (ET).

Major finding: After a median follow-up of 17.9 months, both progression-free survival (P = .43) and overall survival (P = .41) were not significantly different between patients with low and no ERBB2 expression.

Study details: Findings are from an analysis of 1585 patients with HR+ metastatic BC treated with TT+ET from an institutional review board-approved breast cancer database, of which 572 and 1013 patients had no and low ERBB2 expression, respectively.

Disclosures: This study was supported by the National Cancer Institute and other sources. Some authors declared receiving personal fees, grants, or nonfinancial support from several sources.

Source: Mouabbi JA et al. Survival outcomes in patients with hormone receptor-positive metastatic breast cancer with low or no ERBB2 expression treated with targeted therapies plus endocrine therapy. JAMA Netw Open. 2023;6:e2313017 (May 11). doi: 10.1001/jamanetworkopen.2023.13017

Key clinical point: Low vs no human epidermal growth factor receptor 2 (ERBB2, aka HER2) expression had no impact on survival outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (BC) who were treated with targeted therapy (TT) plus endocrine therapy (ET).

Major finding: After a median follow-up of 17.9 months, both progression-free survival (P = .43) and overall survival (P = .41) were not significantly different between patients with low and no ERBB2 expression.

Study details: Findings are from an analysis of 1585 patients with HR+ metastatic BC treated with TT+ET from an institutional review board-approved breast cancer database, of which 572 and 1013 patients had no and low ERBB2 expression, respectively.

Disclosures: This study was supported by the National Cancer Institute and other sources. Some authors declared receiving personal fees, grants, or nonfinancial support from several sources.

Source: Mouabbi JA et al. Survival outcomes in patients with hormone receptor-positive metastatic breast cancer with low or no ERBB2 expression treated with targeted therapies plus endocrine therapy. JAMA Netw Open. 2023;6:e2313017 (May 11). doi: 10.1001/jamanetworkopen.2023.13017

Key clinical point: Low vs no human epidermal growth factor receptor 2 (ERBB2, aka HER2) expression had no impact on survival outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (BC) who were treated with targeted therapy (TT) plus endocrine therapy (ET).

Major finding: After a median follow-up of 17.9 months, both progression-free survival (P = .43) and overall survival (P = .41) were not significantly different between patients with low and no ERBB2 expression.

Study details: Findings are from an analysis of 1585 patients with HR+ metastatic BC treated with TT+ET from an institutional review board-approved breast cancer database, of which 572 and 1013 patients had no and low ERBB2 expression, respectively.

Disclosures: This study was supported by the National Cancer Institute and other sources. Some authors declared receiving personal fees, grants, or nonfinancial support from several sources.

Source: Mouabbi JA et al. Survival outcomes in patients with hormone receptor-positive metastatic breast cancer with low or no ERBB2 expression treated with targeted therapies plus endocrine therapy. JAMA Netw Open. 2023;6:e2313017 (May 11). doi: 10.1001/jamanetworkopen.2023.13017

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

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

CHICAGO – Oncologist Denise Yardley, MD, isn’t used to expressing uncertainty when she tells patients about what’s in store for them in terms of drug treatment. But things are dramatically different now amid a severe national shortage of carboplatin and cisplatin, two common and crucial cancer drugs.

“There’s a regimen I’m thinking about,” Dr. Yardley told a new patient recently, “but we’ll have to wait until you finish your staging evaluation to see whether I can deliver this. Another regimen that’s a little more toxic is my second choice.” And, she added, the alternative chemotherapy treatment – anthracycline instead of carboplatin – requires a longer treatment period.

This ambiguity is hardly ideal, said Dr. Yardley, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville. “It’s another factor in being overwhelmed in a first-time visit and wanting to know the details about what your treatment is going to look like. You’re not walking out knowing exactly what you’re going to take or the exact timing so you can start mapping out your calendar and work schedule.”

This kind of scenario is becoming all too familiar this spring, according to oncologists who gathered at the annual meeting of the American Society of Clinical Oncology (ASCO). In interviews, these physicians said the limited supply of multiple cancer drugs – including the chemotherapies carboplatin and cisplatin – is having an unprecedented negative effect since their use is so widespread in cancer care.

“Every patient could get impacted. That’s why we need to address this sooner rather than later,” said oncologist Aditya Baria, MBBS, MPH, director of the Breast Cancer Research Program at Massachusetts General Hospital, Boston.

Shortages of cancer drugs are not unusual. Three-quarters of oncology pharmacists at 68 organizations surveyed from 2019 to 2020 said shortages prompted treatment delays, reduced doses, or alternative regimens. But the current shortages are having a much wider impact.

The National Comprehensive Cancer Network recently reported that 93% of 27 member institutions surveyed in late May are short on carboplatin, and 70% have reported a shortage of cisplatin. Plus, 20% of 19 centers said they weren’t able to continue carboplatin regimens for all patients. 

The drugs are mainstays of multiple types of treatment for a long list of cancer types including lung, breast, gynecologic, and many others.

Several scenarios are possible when the drugs are in short supply, said Dr. Yardley, who noted that the shortage is more severe than any she’s seen in her medical career of more than 3 decades. Patients may need to be switched to regimens with more side effects, even when they’re in the middle of a treatment, she said. Or patients might have to go longer between treatments.

In some cases, Dr. Yardley said, the shortage is forcing patients to go without an important component of a larger combination therapy regimen. “The Keynote 522 neoadjuvant regimen for triple-negative breast cancer has carboplatin given with Taxol [paclitaxel] and Keytruda [pembrolizumab]. We are just deleting the carboplatin.”

She added that carboplatin is part of the following so-called TCHP regimen for HER2+ early-stage breast cancer: Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), and Perjeta (pertuzumab).

“You can delete [carboplatin] or consider substituting cyclophosphamide for carboplatin,” she said. But she cautioned the Keynote 522 and TCHP regimens haven’t been tested without carboplatin in curative-intent trials.

At Duke University in Durham, N.C., doses of carboplatin for many patients are being lowered by a third to the level that’s commonly used for older and frail patients, said oncologist Arif Kamal, MD, MBA, MHS, who works at the academic center and is the chief patient officer at the American Cancer Society.

“We don’t know if [the lower doses will negatively affect cancer patients’ outcomes]. What’s amazing is how many patients [are understanding about having to take smaller amounts of the chemotherapy],” he said.

Medical organizations are offering guidance. The Society of Gynecologic Oncology, for example, in late April recommended that oncologists increase intervals between chemotherapy treatments when appropriate, round down vial sizes to ensure “efficient use,” and eliminate or minimize use of cisplatin and carboplatin in certain platinum-resistant cancers.

In early June, ASCO published guidance regarding alternatives to cisplatin, carboplatin, and 5-fluorouracil, which is also in short supply, in gastrointestinal cancer. As the guidance notes, some alternatives are more untested or more toxic than ideal treatments.

In addition, ASCO has a webpage devoted to news and resources about shortages of cancer drugs. It offers drug availability updates, general guidance, and breast cancer guidance. ASCO also offers ethical guidance about handling drug shortages.

Patients in clinical trials and those who hope to join them are especially vulnerable to the drug shortage, oncologists interviewed for this story said. Cisplatin and carboplatin are the backbones of many clinical trials, Dr. Yardley said. “When you can’t supply a drug in one of the [trial] arms, that puts the whole trial on pause.”

Even clinics that have managed to find adequate supplies of the drugs are planning for when they run out.

“Our institution and other institutions are trying to come up with a rationing protocol, deciding which patients are going to get access, and which ones have reasonable alternatives,” radiation oncologist Corey Speers MD, PhD, of University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, said in an interview. “In some settings, there really isn’t an effective alternative. Or the alternatives are tens of thousands of dollars more expensive.”

Oncologists also noted that cisplatin and carboplatin aren’t the only cancer drugs in short supply.

“Methotrexate is critically low, and 5FU [fluorouracil] is critically low,” Dr. Yardley said, referring to drugs that each treat several types of cancer. According to the May NCNN survey, 67% of respondents reported low supplies of methotrexate, and 26% said they were low on 5FU.

“Viscous lidocaine is a component of many supportive care mouth rinses for the stomatitis caused by our drugs but is not available at all,” Dr. Yardley said. 

She added that there are also low supplies of fludarabine, which is used to treat chronic lymphocytic lymphom; clofarabine, which is used to treat acute lymphoblastic leukemia; and rasburicase, which is used to treat high levels of uric acid in patients on chemotherapy.

Dr. Speers said his institution is facing a shortage of capecitabine, which is used to treat several types of cancer.

“Numerous trials have demonstrated the improved, safety, efficacy, and convenience of oral capecitabine. With the shortage we’re having to use infusional 5FU, which not only is less convenient but also ends up being more costly and requires infusion room space or continuous infusion pumps. This impacts our ability to treat cancer patients,” he said. “Our capacity is becoming more limited to accommodate these added patients, and we have to use infusional formulations of a drug that previously was readily available via an oral formulation. Patients and caregivers now have to come to the cancer center for appointments and infusions that previously weren’t needed as they could take an oral pill.”

Dr. Speers added that his institution is rationing methotrexate. “We are now prioritizing patients being treated with curative intent and adjusting protocols to use the lowest allowable doses to conserve supply,” he said.

The roots of the platinum chemotherapy drug shortage link back to the India-based Intas Pharmaceuticals company, a major manufacturer of cisplatin and carboplatin. According to Kellyann Zuzulo, spokeperson for Accord Healthcare, an Instas U.S. subsidiary, a facility inspection in December 2022 prompted a decision to temporarily stop making the drugs. The inspection identified multiple problems.

“Intas and Accord are working with the FDA on a plan to return to manufacturing,” Ms. Zuzulo said in an interview. “This will allow for continued production of products that will be prioritized based on medical necessity. A date has not yet been confirmed in which the facility will return to manufacturing for cisplatin, carboplatin or any other products.”

Ms. Zuzulo said the company is not a health care provider and cannot offer advice to patients about alternatives.

Other companies that make cisplatin and carboplatin have also reported shortages. In interviews, representatives for Fresenius Kabi and Pfizer said the companies have limited supplies because of increased demand – not because of manufacturing problems.

On June 12, the American Society of Health-System Pharmacists (ASHP) reported that carboplatin remains in short supply, with all five companies that sell the drug listed as having limited or back-ordered supplies. Cisplatin is also in short supply, the organization reported in a June 9 update, although some is available.

In a June 12 update on methotrexate, ASHP said manufacturing delays at Accord have caused a shortage, and other companies are running low due to increased demand.

As for the future, Congress and the Biden administration, according to a report by Bloomberg, are trying to figure out what to do regarding shortages of cheap generic drugs such as cisplatin and carboplatin. The FDA is exploring a partnership with a Chinese drugmaker to make cisplatin, NBC News reported.

However, fixes will be challenging, according to former FDA commissioner and Pfizer board member, Scott Gottlieb, MD.

“This generic business, particularly for these complex drugs, these complex formulations, is not a healthy business right now. Yet it’s a vital business from a public standpoint,” he told CBS News.

In an interview, Dr. Kamal said that there is even talk about boosting the prices of cheap generic drugs “to ensure that there’s enough incentive for multiple manufacturers to be involved.”

Dr. Kamal said he is crossing his fingers that cutting chemotherapy doses at his clinic doesn’t result in worse outcomes for his patients.

“Right now, I think dropping someone by 25% or 30% is okay. And for some patients, particularly in a curative setting, we try to keep them at as much as 100% as possible. But there’s just a lot of unknowns,” he said.

CHICAGO – Oncologist Denise Yardley, MD, isn’t used to expressing uncertainty when she tells patients about what’s in store for them in terms of drug treatment. But things are dramatically different now amid a severe national shortage of carboplatin and cisplatin, two common and crucial cancer drugs.

“There’s a regimen I’m thinking about,” Dr. Yardley told a new patient recently, “but we’ll have to wait until you finish your staging evaluation to see whether I can deliver this. Another regimen that’s a little more toxic is my second choice.” And, she added, the alternative chemotherapy treatment – anthracycline instead of carboplatin – requires a longer treatment period.

This ambiguity is hardly ideal, said Dr. Yardley, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville. “It’s another factor in being overwhelmed in a first-time visit and wanting to know the details about what your treatment is going to look like. You’re not walking out knowing exactly what you’re going to take or the exact timing so you can start mapping out your calendar and work schedule.”

This kind of scenario is becoming all too familiar this spring, according to oncologists who gathered at the annual meeting of the American Society of Clinical Oncology (ASCO). In interviews, these physicians said the limited supply of multiple cancer drugs – including the chemotherapies carboplatin and cisplatin – is having an unprecedented negative effect since their use is so widespread in cancer care.

“Every patient could get impacted. That’s why we need to address this sooner rather than later,” said oncologist Aditya Baria, MBBS, MPH, director of the Breast Cancer Research Program at Massachusetts General Hospital, Boston.

Shortages of cancer drugs are not unusual. Three-quarters of oncology pharmacists at 68 organizations surveyed from 2019 to 2020 said shortages prompted treatment delays, reduced doses, or alternative regimens. But the current shortages are having a much wider impact.

The National Comprehensive Cancer Network recently reported that 93% of 27 member institutions surveyed in late May are short on carboplatin, and 70% have reported a shortage of cisplatin. Plus, 20% of 19 centers said they weren’t able to continue carboplatin regimens for all patients. 

The drugs are mainstays of multiple types of treatment for a long list of cancer types including lung, breast, gynecologic, and many others.

Several scenarios are possible when the drugs are in short supply, said Dr. Yardley, who noted that the shortage is more severe than any she’s seen in her medical career of more than 3 decades. Patients may need to be switched to regimens with more side effects, even when they’re in the middle of a treatment, she said. Or patients might have to go longer between treatments.

In some cases, Dr. Yardley said, the shortage is forcing patients to go without an important component of a larger combination therapy regimen. “The Keynote 522 neoadjuvant regimen for triple-negative breast cancer has carboplatin given with Taxol [paclitaxel] and Keytruda [pembrolizumab]. We are just deleting the carboplatin.”

She added that carboplatin is part of the following so-called TCHP regimen for HER2+ early-stage breast cancer: Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), and Perjeta (pertuzumab).

“You can delete [carboplatin] or consider substituting cyclophosphamide for carboplatin,” she said. But she cautioned the Keynote 522 and TCHP regimens haven’t been tested without carboplatin in curative-intent trials.

At Duke University in Durham, N.C., doses of carboplatin for many patients are being lowered by a third to the level that’s commonly used for older and frail patients, said oncologist Arif Kamal, MD, MBA, MHS, who works at the academic center and is the chief patient officer at the American Cancer Society.

“We don’t know if [the lower doses will negatively affect cancer patients’ outcomes]. What’s amazing is how many patients [are understanding about having to take smaller amounts of the chemotherapy],” he said.

Medical organizations are offering guidance. The Society of Gynecologic Oncology, for example, in late April recommended that oncologists increase intervals between chemotherapy treatments when appropriate, round down vial sizes to ensure “efficient use,” and eliminate or minimize use of cisplatin and carboplatin in certain platinum-resistant cancers.

In early June, ASCO published guidance regarding alternatives to cisplatin, carboplatin, and 5-fluorouracil, which is also in short supply, in gastrointestinal cancer. As the guidance notes, some alternatives are more untested or more toxic than ideal treatments.

In addition, ASCO has a webpage devoted to news and resources about shortages of cancer drugs. It offers drug availability updates, general guidance, and breast cancer guidance. ASCO also offers ethical guidance about handling drug shortages.

Patients in clinical trials and those who hope to join them are especially vulnerable to the drug shortage, oncologists interviewed for this story said. Cisplatin and carboplatin are the backbones of many clinical trials, Dr. Yardley said. “When you can’t supply a drug in one of the [trial] arms, that puts the whole trial on pause.”

Even clinics that have managed to find adequate supplies of the drugs are planning for when they run out.

“Our institution and other institutions are trying to come up with a rationing protocol, deciding which patients are going to get access, and which ones have reasonable alternatives,” radiation oncologist Corey Speers MD, PhD, of University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, said in an interview. “In some settings, there really isn’t an effective alternative. Or the alternatives are tens of thousands of dollars more expensive.”

Oncologists also noted that cisplatin and carboplatin aren’t the only cancer drugs in short supply.

“Methotrexate is critically low, and 5FU [fluorouracil] is critically low,” Dr. Yardley said, referring to drugs that each treat several types of cancer. According to the May NCNN survey, 67% of respondents reported low supplies of methotrexate, and 26% said they were low on 5FU.

“Viscous lidocaine is a component of many supportive care mouth rinses for the stomatitis caused by our drugs but is not available at all,” Dr. Yardley said. 

She added that there are also low supplies of fludarabine, which is used to treat chronic lymphocytic lymphom; clofarabine, which is used to treat acute lymphoblastic leukemia; and rasburicase, which is used to treat high levels of uric acid in patients on chemotherapy.

Dr. Speers said his institution is facing a shortage of capecitabine, which is used to treat several types of cancer.

“Numerous trials have demonstrated the improved, safety, efficacy, and convenience of oral capecitabine. With the shortage we’re having to use infusional 5FU, which not only is less convenient but also ends up being more costly and requires infusion room space or continuous infusion pumps. This impacts our ability to treat cancer patients,” he said. “Our capacity is becoming more limited to accommodate these added patients, and we have to use infusional formulations of a drug that previously was readily available via an oral formulation. Patients and caregivers now have to come to the cancer center for appointments and infusions that previously weren’t needed as they could take an oral pill.”

Dr. Speers added that his institution is rationing methotrexate. “We are now prioritizing patients being treated with curative intent and adjusting protocols to use the lowest allowable doses to conserve supply,” he said.

The roots of the platinum chemotherapy drug shortage link back to the India-based Intas Pharmaceuticals company, a major manufacturer of cisplatin and carboplatin. According to Kellyann Zuzulo, spokeperson for Accord Healthcare, an Instas U.S. subsidiary, a facility inspection in December 2022 prompted a decision to temporarily stop making the drugs. The inspection identified multiple problems.

“Intas and Accord are working with the FDA on a plan to return to manufacturing,” Ms. Zuzulo said in an interview. “This will allow for continued production of products that will be prioritized based on medical necessity. A date has not yet been confirmed in which the facility will return to manufacturing for cisplatin, carboplatin or any other products.”

Ms. Zuzulo said the company is not a health care provider and cannot offer advice to patients about alternatives.

Other companies that make cisplatin and carboplatin have also reported shortages. In interviews, representatives for Fresenius Kabi and Pfizer said the companies have limited supplies because of increased demand – not because of manufacturing problems.

On June 12, the American Society of Health-System Pharmacists (ASHP) reported that carboplatin remains in short supply, with all five companies that sell the drug listed as having limited or back-ordered supplies. Cisplatin is also in short supply, the organization reported in a June 9 update, although some is available.

In a June 12 update on methotrexate, ASHP said manufacturing delays at Accord have caused a shortage, and other companies are running low due to increased demand.

As for the future, Congress and the Biden administration, according to a report by Bloomberg, are trying to figure out what to do regarding shortages of cheap generic drugs such as cisplatin and carboplatin. The FDA is exploring a partnership with a Chinese drugmaker to make cisplatin, NBC News reported.

However, fixes will be challenging, according to former FDA commissioner and Pfizer board member, Scott Gottlieb, MD.

“This generic business, particularly for these complex drugs, these complex formulations, is not a healthy business right now. Yet it’s a vital business from a public standpoint,” he told CBS News.

In an interview, Dr. Kamal said that there is even talk about boosting the prices of cheap generic drugs “to ensure that there’s enough incentive for multiple manufacturers to be involved.”

Dr. Kamal said he is crossing his fingers that cutting chemotherapy doses at his clinic doesn’t result in worse outcomes for his patients.

“Right now, I think dropping someone by 25% or 30% is okay. And for some patients, particularly in a curative setting, we try to keep them at as much as 100% as possible. But there’s just a lot of unknowns,” he said.

CHICAGO – Oncologist Denise Yardley, MD, isn’t used to expressing uncertainty when she tells patients about what’s in store for them in terms of drug treatment. But things are dramatically different now amid a severe national shortage of carboplatin and cisplatin, two common and crucial cancer drugs.

“There’s a regimen I’m thinking about,” Dr. Yardley told a new patient recently, “but we’ll have to wait until you finish your staging evaluation to see whether I can deliver this. Another regimen that’s a little more toxic is my second choice.” And, she added, the alternative chemotherapy treatment – anthracycline instead of carboplatin – requires a longer treatment period.

This ambiguity is hardly ideal, said Dr. Yardley, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville. “It’s another factor in being overwhelmed in a first-time visit and wanting to know the details about what your treatment is going to look like. You’re not walking out knowing exactly what you’re going to take or the exact timing so you can start mapping out your calendar and work schedule.”

This kind of scenario is becoming all too familiar this spring, according to oncologists who gathered at the annual meeting of the American Society of Clinical Oncology (ASCO). In interviews, these physicians said the limited supply of multiple cancer drugs – including the chemotherapies carboplatin and cisplatin – is having an unprecedented negative effect since their use is so widespread in cancer care.

“Every patient could get impacted. That’s why we need to address this sooner rather than later,” said oncologist Aditya Baria, MBBS, MPH, director of the Breast Cancer Research Program at Massachusetts General Hospital, Boston.

Shortages of cancer drugs are not unusual. Three-quarters of oncology pharmacists at 68 organizations surveyed from 2019 to 2020 said shortages prompted treatment delays, reduced doses, or alternative regimens. But the current shortages are having a much wider impact.

The National Comprehensive Cancer Network recently reported that 93% of 27 member institutions surveyed in late May are short on carboplatin, and 70% have reported a shortage of cisplatin. Plus, 20% of 19 centers said they weren’t able to continue carboplatin regimens for all patients. 

The drugs are mainstays of multiple types of treatment for a long list of cancer types including lung, breast, gynecologic, and many others.

Several scenarios are possible when the drugs are in short supply, said Dr. Yardley, who noted that the shortage is more severe than any she’s seen in her medical career of more than 3 decades. Patients may need to be switched to regimens with more side effects, even when they’re in the middle of a treatment, she said. Or patients might have to go longer between treatments.

In some cases, Dr. Yardley said, the shortage is forcing patients to go without an important component of a larger combination therapy regimen. “The Keynote 522 neoadjuvant regimen for triple-negative breast cancer has carboplatin given with Taxol [paclitaxel] and Keytruda [pembrolizumab]. We are just deleting the carboplatin.”

She added that carboplatin is part of the following so-called TCHP regimen for HER2+ early-stage breast cancer: Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), and Perjeta (pertuzumab).

“You can delete [carboplatin] or consider substituting cyclophosphamide for carboplatin,” she said. But she cautioned the Keynote 522 and TCHP regimens haven’t been tested without carboplatin in curative-intent trials.

At Duke University in Durham, N.C., doses of carboplatin for many patients are being lowered by a third to the level that’s commonly used for older and frail patients, said oncologist Arif Kamal, MD, MBA, MHS, who works at the academic center and is the chief patient officer at the American Cancer Society.

“We don’t know if [the lower doses will negatively affect cancer patients’ outcomes]. What’s amazing is how many patients [are understanding about having to take smaller amounts of the chemotherapy],” he said.

Medical organizations are offering guidance. The Society of Gynecologic Oncology, for example, in late April recommended that oncologists increase intervals between chemotherapy treatments when appropriate, round down vial sizes to ensure “efficient use,” and eliminate or minimize use of cisplatin and carboplatin in certain platinum-resistant cancers.

In early June, ASCO published guidance regarding alternatives to cisplatin, carboplatin, and 5-fluorouracil, which is also in short supply, in gastrointestinal cancer. As the guidance notes, some alternatives are more untested or more toxic than ideal treatments.

In addition, ASCO has a webpage devoted to news and resources about shortages of cancer drugs. It offers drug availability updates, general guidance, and breast cancer guidance. ASCO also offers ethical guidance about handling drug shortages.

Patients in clinical trials and those who hope to join them are especially vulnerable to the drug shortage, oncologists interviewed for this story said. Cisplatin and carboplatin are the backbones of many clinical trials, Dr. Yardley said. “When you can’t supply a drug in one of the [trial] arms, that puts the whole trial on pause.”

Even clinics that have managed to find adequate supplies of the drugs are planning for when they run out.

“Our institution and other institutions are trying to come up with a rationing protocol, deciding which patients are going to get access, and which ones have reasonable alternatives,” radiation oncologist Corey Speers MD, PhD, of University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, said in an interview. “In some settings, there really isn’t an effective alternative. Or the alternatives are tens of thousands of dollars more expensive.”

Oncologists also noted that cisplatin and carboplatin aren’t the only cancer drugs in short supply.

“Methotrexate is critically low, and 5FU [fluorouracil] is critically low,” Dr. Yardley said, referring to drugs that each treat several types of cancer. According to the May NCNN survey, 67% of respondents reported low supplies of methotrexate, and 26% said they were low on 5FU.

“Viscous lidocaine is a component of many supportive care mouth rinses for the stomatitis caused by our drugs but is not available at all,” Dr. Yardley said. 

She added that there are also low supplies of fludarabine, which is used to treat chronic lymphocytic lymphom; clofarabine, which is used to treat acute lymphoblastic leukemia; and rasburicase, which is used to treat high levels of uric acid in patients on chemotherapy.

Dr. Speers said his institution is facing a shortage of capecitabine, which is used to treat several types of cancer.

“Numerous trials have demonstrated the improved, safety, efficacy, and convenience of oral capecitabine. With the shortage we’re having to use infusional 5FU, which not only is less convenient but also ends up being more costly and requires infusion room space or continuous infusion pumps. This impacts our ability to treat cancer patients,” he said. “Our capacity is becoming more limited to accommodate these added patients, and we have to use infusional formulations of a drug that previously was readily available via an oral formulation. Patients and caregivers now have to come to the cancer center for appointments and infusions that previously weren’t needed as they could take an oral pill.”

Dr. Speers added that his institution is rationing methotrexate. “We are now prioritizing patients being treated with curative intent and adjusting protocols to use the lowest allowable doses to conserve supply,” he said.

The roots of the platinum chemotherapy drug shortage link back to the India-based Intas Pharmaceuticals company, a major manufacturer of cisplatin and carboplatin. According to Kellyann Zuzulo, spokeperson for Accord Healthcare, an Instas U.S. subsidiary, a facility inspection in December 2022 prompted a decision to temporarily stop making the drugs. The inspection identified multiple problems.

“Intas and Accord are working with the FDA on a plan to return to manufacturing,” Ms. Zuzulo said in an interview. “This will allow for continued production of products that will be prioritized based on medical necessity. A date has not yet been confirmed in which the facility will return to manufacturing for cisplatin, carboplatin or any other products.”

Ms. Zuzulo said the company is not a health care provider and cannot offer advice to patients about alternatives.

Other companies that make cisplatin and carboplatin have also reported shortages. In interviews, representatives for Fresenius Kabi and Pfizer said the companies have limited supplies because of increased demand – not because of manufacturing problems.

On June 12, the American Society of Health-System Pharmacists (ASHP) reported that carboplatin remains in short supply, with all five companies that sell the drug listed as having limited or back-ordered supplies. Cisplatin is also in short supply, the organization reported in a June 9 update, although some is available.

In a June 12 update on methotrexate, ASHP said manufacturing delays at Accord have caused a shortage, and other companies are running low due to increased demand.

As for the future, Congress and the Biden administration, according to a report by Bloomberg, are trying to figure out what to do regarding shortages of cheap generic drugs such as cisplatin and carboplatin. The FDA is exploring a partnership with a Chinese drugmaker to make cisplatin, NBC News reported.

However, fixes will be challenging, according to former FDA commissioner and Pfizer board member, Scott Gottlieb, MD.

“This generic business, particularly for these complex drugs, these complex formulations, is not a healthy business right now. Yet it’s a vital business from a public standpoint,” he told CBS News.

In an interview, Dr. Kamal said that there is even talk about boosting the prices of cheap generic drugs “to ensure that there’s enough incentive for multiple manufacturers to be involved.”

Dr. Kamal said he is crossing his fingers that cutting chemotherapy doses at his clinic doesn’t result in worse outcomes for his patients.

“Right now, I think dropping someone by 25% or 30% is okay. And for some patients, particularly in a curative setting, we try to keep them at as much as 100% as possible. But there’s just a lot of unknowns,” he said.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

In metastatic breast cancer, a fixed dose of capecitabine given on a 7-day-on, 7-day-off schedule had similar efficacy and reduced adverse events compared with the standard 14-day-on, 7-day-off schedule, in a new study.

Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.

The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m², but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.

The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m² dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.

Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).

The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.

The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
 

Findings back up clinical practice

“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.

Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.

During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
 

Fixed dose versus body surface area

Dr. Kirshner also said his practice uses a dose of 1 g/m² of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m².”

Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”

Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”

Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.

Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.

In metastatic breast cancer, a fixed dose of capecitabine given on a 7-day-on, 7-day-off schedule had similar efficacy and reduced adverse events compared with the standard 14-day-on, 7-day-off schedule, in a new study.

Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.

The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m², but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.

The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m² dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.

Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).

The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.

The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
 

Findings back up clinical practice

“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.

Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.

During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
 

Fixed dose versus body surface area

Dr. Kirshner also said his practice uses a dose of 1 g/m² of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m².”

Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”

Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”

Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.

Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.

In metastatic breast cancer, a fixed dose of capecitabine given on a 7-day-on, 7-day-off schedule had similar efficacy and reduced adverse events compared with the standard 14-day-on, 7-day-off schedule, in a new study.

Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.

The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m², but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.

The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m² dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.

Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).

The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.

The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
 

Findings back up clinical practice

“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.

Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.

During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
 

Fixed dose versus body surface area

Dr. Kirshner also said his practice uses a dose of 1 g/m² of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m².”

Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”

Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”

Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.

Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.