Key clinical point: Addition of palbociclib to adjuvant endocrine therapy (ET) vs. ET alone failed to improve invasive disease-free survival (IDFS) in patients with early-stage hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer.

Major finding: At the median follow-up of 23.7 months, 3-year IDFS was similar for palbociclib + ET and ET alone groups (88.2% vs. 88.5%; hazard ratio, 0.93; log-rank P = .51). Serious adverse events occurred in 12.4% of patients on palbociclib + ET vs. 7.6% on ET alone.

Study details: Findings are from the second interim analysis of the ongoing phase 3 PALLAS trial that randomly allocated 5,760 patients with stage II-III HR+ and HER2− breast cancer to receive either 2 years of palbociclib in addition to ongoing standard adjuvant ET (n = 2,883) or ongoing standard adjuvant ET alone (n = 2,877).

Disclosures: PALLAS trial was cosponsored by the Alliance Foundation Trials and the Austrian Breast and Colorectal Cancer Study Group, in collaboration with Eastern Cooperative Oncology Group, the National Surgical Adjuvant Breast and Bowel Project, the German Breast Group, and the Breast International Group, with funding from Pfizer. The lead author reported receiving personal fees from Eisai, Lilly, and Novartis. Some of the coinvestigators reported ties with various pharmaceutical companies including Pfizer.

Source: Mayer EL et al. Lancet Oncol. 2021 Jan 15. doi: 10.1016/S1470-2045(20)30642-2.

Key clinical point: Addition of palbociclib to adjuvant endocrine therapy (ET) vs. ET alone failed to improve invasive disease-free survival (IDFS) in patients with early-stage hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer.

Major finding: At the median follow-up of 23.7 months, 3-year IDFS was similar for palbociclib + ET and ET alone groups (88.2% vs. 88.5%; hazard ratio, 0.93; log-rank P = .51). Serious adverse events occurred in 12.4% of patients on palbociclib + ET vs. 7.6% on ET alone.

Study details: Findings are from the second interim analysis of the ongoing phase 3 PALLAS trial that randomly allocated 5,760 patients with stage II-III HR+ and HER2− breast cancer to receive either 2 years of palbociclib in addition to ongoing standard adjuvant ET (n = 2,883) or ongoing standard adjuvant ET alone (n = 2,877).

Disclosures: PALLAS trial was cosponsored by the Alliance Foundation Trials and the Austrian Breast and Colorectal Cancer Study Group, in collaboration with Eastern Cooperative Oncology Group, the National Surgical Adjuvant Breast and Bowel Project, the German Breast Group, and the Breast International Group, with funding from Pfizer. The lead author reported receiving personal fees from Eisai, Lilly, and Novartis. Some of the coinvestigators reported ties with various pharmaceutical companies including Pfizer.

Source: Mayer EL et al. Lancet Oncol. 2021 Jan 15. doi: 10.1016/S1470-2045(20)30642-2.

Key clinical point: Addition of palbociclib to adjuvant endocrine therapy (ET) vs. ET alone failed to improve invasive disease-free survival (IDFS) in patients with early-stage hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer.

Major finding: At the median follow-up of 23.7 months, 3-year IDFS was similar for palbociclib + ET and ET alone groups (88.2% vs. 88.5%; hazard ratio, 0.93; log-rank P = .51). Serious adverse events occurred in 12.4% of patients on palbociclib + ET vs. 7.6% on ET alone.

Study details: Findings are from the second interim analysis of the ongoing phase 3 PALLAS trial that randomly allocated 5,760 patients with stage II-III HR+ and HER2− breast cancer to receive either 2 years of palbociclib in addition to ongoing standard adjuvant ET (n = 2,883) or ongoing standard adjuvant ET alone (n = 2,877).

Disclosures: PALLAS trial was cosponsored by the Alliance Foundation Trials and the Austrian Breast and Colorectal Cancer Study Group, in collaboration with Eastern Cooperative Oncology Group, the National Surgical Adjuvant Breast and Bowel Project, the German Breast Group, and the Breast International Group, with funding from Pfizer. The lead author reported receiving personal fees from Eisai, Lilly, and Novartis. Some of the coinvestigators reported ties with various pharmaceutical companies including Pfizer.

Source: Mayer EL et al. Lancet Oncol. 2021 Jan 15. doi: 10.1016/S1470-2045(20)30642-2.

Key clinical point: Margetuximab + chemotherapy vs. trastuzumab + chemotherapy improved progression-free survival (PFS) with an acceptable safety profile in patients with ERBB2-positive advanced breast cancer (ERBB2+ ABC) who progressed on 2 or more prior anti-ERBB2 therapies.

Major finding: Margetuximab + chemotherapy prolonged PFS with a 24% relative risk reduction vs. trastuzumab + chemotherapy (median PFS, 5.8 vs. 4.9 months; hazard ratio, 0.76; P = .03). Safety was comparable between the groups. Infusion-related reactions were higher with margetuximab vs. trastuzumab (13.3% vs. 3.4%; P less than .001) but were mostly prevalent at cycle 1 and resolved within 24 hours.

Study details: Findings are from the phase 3 SOPHIA trial including 536 patients with ERBB2+ ABC who had progressive disease after 2 or more prior anti-ERBB2 therapies. Patients were randomly allocated to receive either margetuximab + chemotherapy (n = 266) or trastuzumab + chemotherapy (n = 270).

Disclosures: This study was supported by MacroGenics, Inc. The lead author reported ties with MacroGenics, Roche, Pfizer, Novartis, Lilly, Merck, Seattle Genetics, Odonate Therapeutics, Eisai, Sermonix Pharmaceuticals, Immunomedics, Daiichi Sankyo, Puma, and Samsung. Other investigators reported owning stocks of, being an employee of, receiving support from, and/or consulting for various pharmaceutical companies including MacroGenics.

Source: Rugo HS et al. JAMA Oncol. 2021 Jan 22. doi: 10.1001/jamaoncol.2020.7932.

Key clinical point: Margetuximab + chemotherapy vs. trastuzumab + chemotherapy improved progression-free survival (PFS) with an acceptable safety profile in patients with ERBB2-positive advanced breast cancer (ERBB2+ ABC) who progressed on 2 or more prior anti-ERBB2 therapies.

Major finding: Margetuximab + chemotherapy prolonged PFS with a 24% relative risk reduction vs. trastuzumab + chemotherapy (median PFS, 5.8 vs. 4.9 months; hazard ratio, 0.76; P = .03). Safety was comparable between the groups. Infusion-related reactions were higher with margetuximab vs. trastuzumab (13.3% vs. 3.4%; P less than .001) but were mostly prevalent at cycle 1 and resolved within 24 hours.

Study details: Findings are from the phase 3 SOPHIA trial including 536 patients with ERBB2+ ABC who had progressive disease after 2 or more prior anti-ERBB2 therapies. Patients were randomly allocated to receive either margetuximab + chemotherapy (n = 266) or trastuzumab + chemotherapy (n = 270).

Disclosures: This study was supported by MacroGenics, Inc. The lead author reported ties with MacroGenics, Roche, Pfizer, Novartis, Lilly, Merck, Seattle Genetics, Odonate Therapeutics, Eisai, Sermonix Pharmaceuticals, Immunomedics, Daiichi Sankyo, Puma, and Samsung. Other investigators reported owning stocks of, being an employee of, receiving support from, and/or consulting for various pharmaceutical companies including MacroGenics.

Source: Rugo HS et al. JAMA Oncol. 2021 Jan 22. doi: 10.1001/jamaoncol.2020.7932.

Key clinical point: Margetuximab + chemotherapy vs. trastuzumab + chemotherapy improved progression-free survival (PFS) with an acceptable safety profile in patients with ERBB2-positive advanced breast cancer (ERBB2+ ABC) who progressed on 2 or more prior anti-ERBB2 therapies.

Major finding: Margetuximab + chemotherapy prolonged PFS with a 24% relative risk reduction vs. trastuzumab + chemotherapy (median PFS, 5.8 vs. 4.9 months; hazard ratio, 0.76; P = .03). Safety was comparable between the groups. Infusion-related reactions were higher with margetuximab vs. trastuzumab (13.3% vs. 3.4%; P less than .001) but were mostly prevalent at cycle 1 and resolved within 24 hours.

Study details: Findings are from the phase 3 SOPHIA trial including 536 patients with ERBB2+ ABC who had progressive disease after 2 or more prior anti-ERBB2 therapies. Patients were randomly allocated to receive either margetuximab + chemotherapy (n = 266) or trastuzumab + chemotherapy (n = 270).

Disclosures: This study was supported by MacroGenics, Inc. The lead author reported ties with MacroGenics, Roche, Pfizer, Novartis, Lilly, Merck, Seattle Genetics, Odonate Therapeutics, Eisai, Sermonix Pharmaceuticals, Immunomedics, Daiichi Sankyo, Puma, and Samsung. Other investigators reported owning stocks of, being an employee of, receiving support from, and/or consulting for various pharmaceutical companies including MacroGenics.

Source: Rugo HS et al. JAMA Oncol. 2021 Jan 22. doi: 10.1001/jamaoncol.2020.7932.

Key clinical point: Paclitaxel dose reduction does not necessarily result in improved neuropathy outcomes in patients with breast cancer prescribed weekly paclitaxel schedules.

Major finding: Patients receiving reduced-dose vs. full-dose paclitaxel had worse patient-reported symptom burden (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, 40.2 vs. 45.9) and clinical neuropathy outcomes (Total Neuropathy Score clinical version, 4.3 vs. 3.3; all P less than .05).

Study details: Findings are from the assessment of women with breast cancer prescribed weekly paclitaxel (80 mg/m²) for 12 weeks. Posttreatment outcomes were assessed at 3.6 months in 105 women who underwent subsequent dose reduction.

Disclosures: This study was supported by grants from the Cancer Institute NSW Program and National Health and Medical Research Council of Australia. M Friedlander reported ties with various pharmaceutical companies. The other authors did not have any financial disclosures.

Source: Timmins HC et al. Oncologist. 2021 Feb 1. doi: 10.1002/onco.13697.

Key clinical point: Paclitaxel dose reduction does not necessarily result in improved neuropathy outcomes in patients with breast cancer prescribed weekly paclitaxel schedules.

Major finding: Patients receiving reduced-dose vs. full-dose paclitaxel had worse patient-reported symptom burden (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, 40.2 vs. 45.9) and clinical neuropathy outcomes (Total Neuropathy Score clinical version, 4.3 vs. 3.3; all P less than .05).

Study details: Findings are from the assessment of women with breast cancer prescribed weekly paclitaxel (80 mg/m²) for 12 weeks. Posttreatment outcomes were assessed at 3.6 months in 105 women who underwent subsequent dose reduction.

Disclosures: This study was supported by grants from the Cancer Institute NSW Program and National Health and Medical Research Council of Australia. M Friedlander reported ties with various pharmaceutical companies. The other authors did not have any financial disclosures.

Source: Timmins HC et al. Oncologist. 2021 Feb 1. doi: 10.1002/onco.13697.

Key clinical point: Paclitaxel dose reduction does not necessarily result in improved neuropathy outcomes in patients with breast cancer prescribed weekly paclitaxel schedules.

Major finding: Patients receiving reduced-dose vs. full-dose paclitaxel had worse patient-reported symptom burden (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, 40.2 vs. 45.9) and clinical neuropathy outcomes (Total Neuropathy Score clinical version, 4.3 vs. 3.3; all P less than .05).

Study details: Findings are from the assessment of women with breast cancer prescribed weekly paclitaxel (80 mg/m²) for 12 weeks. Posttreatment outcomes were assessed at 3.6 months in 105 women who underwent subsequent dose reduction.

Disclosures: This study was supported by grants from the Cancer Institute NSW Program and National Health and Medical Research Council of Australia. M Friedlander reported ties with various pharmaceutical companies. The other authors did not have any financial disclosures.

Source: Timmins HC et al. Oncologist. 2021 Feb 1. doi: 10.1002/onco.13697.

Key clinical point: Intensive screening for distant metastasis during posttreatment follow-up was not associated with improved overall survival (OS) in disease-free patients initially diagnosed with nonmetastatic breast cancer.

Major finding: OS was not significantly different among patients receiving intensive vs. less intensive screening (adjusted hazard ratio, 1.21; P = .124).

Study details: This retrospective study evaluated the effect of intensive (n=199) vs. less intensive (n=199) screening on survival in 398 patients initially diagnosed with nonmetastatic, resectable breast cancer who eventually developed distant metastasis after initial curative treatment.

Disclosures: This study was supported by grants received by the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea, and the National Research Foundation of Korea grant funded by the Ministry of Science and ICT, Republic of Korea. The authors declared no conflicts of interest.

Source: Cheun J-H et al. Sci Rep. 2021 Feb 2. doi: 10.1038/s41598-021-82485-w.

Key clinical point: Intensive screening for distant metastasis during posttreatment follow-up was not associated with improved overall survival (OS) in disease-free patients initially diagnosed with nonmetastatic breast cancer.

Major finding: OS was not significantly different among patients receiving intensive vs. less intensive screening (adjusted hazard ratio, 1.21; P = .124).

Study details: This retrospective study evaluated the effect of intensive (n=199) vs. less intensive (n=199) screening on survival in 398 patients initially diagnosed with nonmetastatic, resectable breast cancer who eventually developed distant metastasis after initial curative treatment.

Disclosures: This study was supported by grants received by the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea, and the National Research Foundation of Korea grant funded by the Ministry of Science and ICT, Republic of Korea. The authors declared no conflicts of interest.

Source: Cheun J-H et al. Sci Rep. 2021 Feb 2. doi: 10.1038/s41598-021-82485-w.

Key clinical point: Intensive screening for distant metastasis during posttreatment follow-up was not associated with improved overall survival (OS) in disease-free patients initially diagnosed with nonmetastatic breast cancer.

Major finding: OS was not significantly different among patients receiving intensive vs. less intensive screening (adjusted hazard ratio, 1.21; P = .124).

Study details: This retrospective study evaluated the effect of intensive (n=199) vs. less intensive (n=199) screening on survival in 398 patients initially diagnosed with nonmetastatic, resectable breast cancer who eventually developed distant metastasis after initial curative treatment.

Disclosures: This study was supported by grants received by the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea, and the National Research Foundation of Korea grant funded by the Ministry of Science and ICT, Republic of Korea. The authors declared no conflicts of interest.

Source: Cheun J-H et al. Sci Rep. 2021 Feb 2. doi: 10.1038/s41598-021-82485-w.

Key clinical point: By opting initially for breast-conserving therapy (BCT) over mastectomy, majority of women with T1-2 node-negative breast cancer with positive sentinel lymph node (SLN) can avoid completion axillary lymph node dissection (cALND), often done in mastectomy.

Major finding: Patients treated with mastectomy vs. BCT were more likely to receive cALND after positive SLN (71% vs. 26.6%; P less than .001). Extracapsular extension (ECE) in the SLN was observed in 31.6% of patients treated with mastectomy and cALND. However, remaining 68.4% of patients without ECE in the SLN could have avoided cALND if they had chosen BCT initially.

Study details: Findings are from an analysis of 306 women with T1-2 clinically node-negative breast cancer with metastases in the SLN who were treated with mastectomy (n=107) or BCT (n=199).

Disclosures: Programmatic support was provided by the Fashion Footwear Charitable Foundation of New York, Inc., the Margie and Robert E. Peterson Foundation, and the Linda and Jim Lippman. ML Smidt reported receiving a grant from Servier Pharma. The remaining authors had no disclosures.

Source: Vane MLG et al. Ann Surg Oncol. 2021 Feb 14. doi: 10.1245/s10434-021-09674-9. 

Key clinical point: By opting initially for breast-conserving therapy (BCT) over mastectomy, majority of women with T1-2 node-negative breast cancer with positive sentinel lymph node (SLN) can avoid completion axillary lymph node dissection (cALND), often done in mastectomy.

Major finding: Patients treated with mastectomy vs. BCT were more likely to receive cALND after positive SLN (71% vs. 26.6%; P less than .001). Extracapsular extension (ECE) in the SLN was observed in 31.6% of patients treated with mastectomy and cALND. However, remaining 68.4% of patients without ECE in the SLN could have avoided cALND if they had chosen BCT initially.

Study details: Findings are from an analysis of 306 women with T1-2 clinically node-negative breast cancer with metastases in the SLN who were treated with mastectomy (n=107) or BCT (n=199).

Disclosures: Programmatic support was provided by the Fashion Footwear Charitable Foundation of New York, Inc., the Margie and Robert E. Peterson Foundation, and the Linda and Jim Lippman. ML Smidt reported receiving a grant from Servier Pharma. The remaining authors had no disclosures.

Source: Vane MLG et al. Ann Surg Oncol. 2021 Feb 14. doi: 10.1245/s10434-021-09674-9. 

Key clinical point: By opting initially for breast-conserving therapy (BCT) over mastectomy, majority of women with T1-2 node-negative breast cancer with positive sentinel lymph node (SLN) can avoid completion axillary lymph node dissection (cALND), often done in mastectomy.

Major finding: Patients treated with mastectomy vs. BCT were more likely to receive cALND after positive SLN (71% vs. 26.6%; P less than .001). Extracapsular extension (ECE) in the SLN was observed in 31.6% of patients treated with mastectomy and cALND. However, remaining 68.4% of patients without ECE in the SLN could have avoided cALND if they had chosen BCT initially.

Study details: Findings are from an analysis of 306 women with T1-2 clinically node-negative breast cancer with metastases in the SLN who were treated with mastectomy (n=107) or BCT (n=199).

Disclosures: Programmatic support was provided by the Fashion Footwear Charitable Foundation of New York, Inc., the Margie and Robert E. Peterson Foundation, and the Linda and Jim Lippman. ML Smidt reported receiving a grant from Servier Pharma. The remaining authors had no disclosures.

Source: Vane MLG et al. Ann Surg Oncol. 2021 Feb 14. doi: 10.1245/s10434-021-09674-9. 

Type 3 von Willebrand disease (VWD) is rare, but this form of the disease is associated with severe bleeding, particularly in muscles and joints, a bleeding disorders expert said.

“There’s a virtually complete deficiency in von Willebrand factor [in type 3 disease], so usually it’s defined as below 5 or in some studies below 3 IU/dL, but also due to the very low levels of von Willebrand factor, there’s also a very low level of factor VIII,” said Jeroen Eikenboom, MD, PhD, from Leiden (the Netherlands) University Medical Center.

“The inheritance pattern is autosomal recessive, and the prevalence is about 1 in a million,” he said during the annual congress of the European Association for Haemophilia and Allied Disorders.

Erik Adolf von Willenbrand, MD, PhD, first described this form of VWD in a family from the Åland Islands, an autonomous region of Finland. The disease, later discovered to be caused in this family by a cytosine deletion in exon 18 of the von Willebrand factor (VWF) gene, was associated with fatal bleeding events in several family members.

“As VWF is the carrier protein of factor VIII, the very low VWF level leads to a strongly reduced factor VIII level, comparable to the levels seen in mild to moderate hemophilia A. As a consequence, VWD type 3 has the combined characteristics of a primary as well as a secondary hemostasis defect,” Dr. Eikenboom explained in an abstract accompanying his talk.

Compared with VWD type 1 or 2, type 3 VWD is associated with bleeding episodes more commonly seen in patients with hemophilia A, notably mucocutaneous bleeding, bleeding after trauma or during surgery, and bleeding into joints and/or muscles.
 

Treatment

The goals of treatment for patients with type 3 VWD are to correct the dual hemostasis defects of impaired platelet adhesion because of low VWF levels, and the intrinsic coagulation defect because of levels of factor VIII.

Desmopressin is not effective in type 3 VWD, Dr. Eikenboom said, so treatment requires the use of either plasma-derived VWF, with or without factor VIII, or recombinant VWF.

In the United States, the only standalone VWF concentrate approved by the Food and Drug Administration is a recombinant product (Vonvendi), Three other human plasma–derived concentrates containing both VWF and factor VIII are also licensed (Alpanate, Humate-P, Wilate).

Clinicians prescribing the combined factor concentrates need to be aware of differences in pharmacokinetics between the products.

For example, following infusion of Wilate, which has equal amounts of von Willebrand factor and factor VIII, there is an increase in circulation of both von Willebrand factor and factor VIII and a similar decline in each factor over time.

In contrast, following an infusion of Humate-P, which contains lower levels of factor VIII, “interestingly, you see a secondary rise of factor VIII in Humate-P–infused patients, whereas the secondary rise is not visible in the Wilate patients,” he said.

Approximately 22% of patients with type 3 VWD also receive prophylaxis with VWF concentrate, which has been shown to decrease the median annualized bleeding rate from 25% to 6.1%.

Dr. Eikenboom cautioned that 5%-10% of patients with type 3 VWD may develop allo-antibodies against VWF concentrates, which can complicate treatment and carries risk of anaphylactic shock.

“It’s also been mentioned in literature that there may be an association with partial or complete von Willebrand factor gene deletions or nonsense mutations and the development of allo-antibodies,” he said.
 

Prophylaxis burdensome but helpful

Veronica H. Flood, MD, from the Medical College of Wisconsin, Milwaukee, who specializes in the treatment of patients with von Willebrand disease, follows a number of both girls and boys with type 3 VWD.

“Those are the people who will have bleeding into their joints, and for the girls, worse periods than some of those with other types of von Willebrand disease, and it is true that if you want to stop their bleeding, you cannot use desmopressin like we use in most other von Willebrand patients. They will need factor, although for the heavy menstrual bleeding you can use hormones or tranexamic acid – there are some other options for that,” she said in an interview.

She also noted that type 3 von Willebrand disease can be highly variable. For patients with especially frequent joint bleeding, her center recommends prophylaxis.

“Prophylaxis can be very burdensome for patients. You’re talking about IV therapy several times a week, but it’s very helpful for the joint bleeds. Episodic prophylaxis can be very helpful for heavy menstrual bleeding, and we actually have type 2, type 3, and some type 1 patients with bad enough nose bleeds that they end up on prophylaxis,” she said.

Patients with gastrointestinal bleeding are the most challenging to care for, she noted.

“You can put them on factor prophylaxis, but even that isn’t always enough to help some adults with bad GI bleeding, and we’re investigating other options for that,” she said.

Dr. Eikenboom disclosed research support from CSL Behring and honoraria (directed to his institution) for educational activities sponsored by Roche and Celgene. Dr. Flood reported having no conflicts of interest to disclose.

Type 3 von Willebrand disease (VWD) is rare, but this form of the disease is associated with severe bleeding, particularly in muscles and joints, a bleeding disorders expert said.

“There’s a virtually complete deficiency in von Willebrand factor [in type 3 disease], so usually it’s defined as below 5 or in some studies below 3 IU/dL, but also due to the very low levels of von Willebrand factor, there’s also a very low level of factor VIII,” said Jeroen Eikenboom, MD, PhD, from Leiden (the Netherlands) University Medical Center.

“The inheritance pattern is autosomal recessive, and the prevalence is about 1 in a million,” he said during the annual congress of the European Association for Haemophilia and Allied Disorders.

Erik Adolf von Willenbrand, MD, PhD, first described this form of VWD in a family from the Åland Islands, an autonomous region of Finland. The disease, later discovered to be caused in this family by a cytosine deletion in exon 18 of the von Willebrand factor (VWF) gene, was associated with fatal bleeding events in several family members.

“As VWF is the carrier protein of factor VIII, the very low VWF level leads to a strongly reduced factor VIII level, comparable to the levels seen in mild to moderate hemophilia A. As a consequence, VWD type 3 has the combined characteristics of a primary as well as a secondary hemostasis defect,” Dr. Eikenboom explained in an abstract accompanying his talk.

Compared with VWD type 1 or 2, type 3 VWD is associated with bleeding episodes more commonly seen in patients with hemophilia A, notably mucocutaneous bleeding, bleeding after trauma or during surgery, and bleeding into joints and/or muscles.
 

Treatment

The goals of treatment for patients with type 3 VWD are to correct the dual hemostasis defects of impaired platelet adhesion because of low VWF levels, and the intrinsic coagulation defect because of levels of factor VIII.

Desmopressin is not effective in type 3 VWD, Dr. Eikenboom said, so treatment requires the use of either plasma-derived VWF, with or without factor VIII, or recombinant VWF.

In the United States, the only standalone VWF concentrate approved by the Food and Drug Administration is a recombinant product (Vonvendi), Three other human plasma–derived concentrates containing both VWF and factor VIII are also licensed (Alpanate, Humate-P, Wilate).

Clinicians prescribing the combined factor concentrates need to be aware of differences in pharmacokinetics between the products.

For example, following infusion of Wilate, which has equal amounts of von Willebrand factor and factor VIII, there is an increase in circulation of both von Willebrand factor and factor VIII and a similar decline in each factor over time.

In contrast, following an infusion of Humate-P, which contains lower levels of factor VIII, “interestingly, you see a secondary rise of factor VIII in Humate-P–infused patients, whereas the secondary rise is not visible in the Wilate patients,” he said.

Approximately 22% of patients with type 3 VWD also receive prophylaxis with VWF concentrate, which has been shown to decrease the median annualized bleeding rate from 25% to 6.1%.

Dr. Eikenboom cautioned that 5%-10% of patients with type 3 VWD may develop allo-antibodies against VWF concentrates, which can complicate treatment and carries risk of anaphylactic shock.

“It’s also been mentioned in literature that there may be an association with partial or complete von Willebrand factor gene deletions or nonsense mutations and the development of allo-antibodies,” he said.
 

Prophylaxis burdensome but helpful

Veronica H. Flood, MD, from the Medical College of Wisconsin, Milwaukee, who specializes in the treatment of patients with von Willebrand disease, follows a number of both girls and boys with type 3 VWD.

“Those are the people who will have bleeding into their joints, and for the girls, worse periods than some of those with other types of von Willebrand disease, and it is true that if you want to stop their bleeding, you cannot use desmopressin like we use in most other von Willebrand patients. They will need factor, although for the heavy menstrual bleeding you can use hormones or tranexamic acid – there are some other options for that,” she said in an interview.

She also noted that type 3 von Willebrand disease can be highly variable. For patients with especially frequent joint bleeding, her center recommends prophylaxis.

“Prophylaxis can be very burdensome for patients. You’re talking about IV therapy several times a week, but it’s very helpful for the joint bleeds. Episodic prophylaxis can be very helpful for heavy menstrual bleeding, and we actually have type 2, type 3, and some type 1 patients with bad enough nose bleeds that they end up on prophylaxis,” she said.

Patients with gastrointestinal bleeding are the most challenging to care for, she noted.

“You can put them on factor prophylaxis, but even that isn’t always enough to help some adults with bad GI bleeding, and we’re investigating other options for that,” she said.

Dr. Eikenboom disclosed research support from CSL Behring and honoraria (directed to his institution) for educational activities sponsored by Roche and Celgene. Dr. Flood reported having no conflicts of interest to disclose.

Type 3 von Willebrand disease (VWD) is rare, but this form of the disease is associated with severe bleeding, particularly in muscles and joints, a bleeding disorders expert said.

“There’s a virtually complete deficiency in von Willebrand factor [in type 3 disease], so usually it’s defined as below 5 or in some studies below 3 IU/dL, but also due to the very low levels of von Willebrand factor, there’s also a very low level of factor VIII,” said Jeroen Eikenboom, MD, PhD, from Leiden (the Netherlands) University Medical Center.

“The inheritance pattern is autosomal recessive, and the prevalence is about 1 in a million,” he said during the annual congress of the European Association for Haemophilia and Allied Disorders.

Erik Adolf von Willenbrand, MD, PhD, first described this form of VWD in a family from the Åland Islands, an autonomous region of Finland. The disease, later discovered to be caused in this family by a cytosine deletion in exon 18 of the von Willebrand factor (VWF) gene, was associated with fatal bleeding events in several family members.

“As VWF is the carrier protein of factor VIII, the very low VWF level leads to a strongly reduced factor VIII level, comparable to the levels seen in mild to moderate hemophilia A. As a consequence, VWD type 3 has the combined characteristics of a primary as well as a secondary hemostasis defect,” Dr. Eikenboom explained in an abstract accompanying his talk.

Compared with VWD type 1 or 2, type 3 VWD is associated with bleeding episodes more commonly seen in patients with hemophilia A, notably mucocutaneous bleeding, bleeding after trauma or during surgery, and bleeding into joints and/or muscles.
 

Treatment

The goals of treatment for patients with type 3 VWD are to correct the dual hemostasis defects of impaired platelet adhesion because of low VWF levels, and the intrinsic coagulation defect because of levels of factor VIII.

Desmopressin is not effective in type 3 VWD, Dr. Eikenboom said, so treatment requires the use of either plasma-derived VWF, with or without factor VIII, or recombinant VWF.

In the United States, the only standalone VWF concentrate approved by the Food and Drug Administration is a recombinant product (Vonvendi), Three other human plasma–derived concentrates containing both VWF and factor VIII are also licensed (Alpanate, Humate-P, Wilate).

Clinicians prescribing the combined factor concentrates need to be aware of differences in pharmacokinetics between the products.

For example, following infusion of Wilate, which has equal amounts of von Willebrand factor and factor VIII, there is an increase in circulation of both von Willebrand factor and factor VIII and a similar decline in each factor over time.

In contrast, following an infusion of Humate-P, which contains lower levels of factor VIII, “interestingly, you see a secondary rise of factor VIII in Humate-P–infused patients, whereas the secondary rise is not visible in the Wilate patients,” he said.

Approximately 22% of patients with type 3 VWD also receive prophylaxis with VWF concentrate, which has been shown to decrease the median annualized bleeding rate from 25% to 6.1%.

Dr. Eikenboom cautioned that 5%-10% of patients with type 3 VWD may develop allo-antibodies against VWF concentrates, which can complicate treatment and carries risk of anaphylactic shock.

“It’s also been mentioned in literature that there may be an association with partial or complete von Willebrand factor gene deletions or nonsense mutations and the development of allo-antibodies,” he said.
 

Prophylaxis burdensome but helpful

Veronica H. Flood, MD, from the Medical College of Wisconsin, Milwaukee, who specializes in the treatment of patients with von Willebrand disease, follows a number of both girls and boys with type 3 VWD.

“Those are the people who will have bleeding into their joints, and for the girls, worse periods than some of those with other types of von Willebrand disease, and it is true that if you want to stop their bleeding, you cannot use desmopressin like we use in most other von Willebrand patients. They will need factor, although for the heavy menstrual bleeding you can use hormones or tranexamic acid – there are some other options for that,” she said in an interview.

She also noted that type 3 von Willebrand disease can be highly variable. For patients with especially frequent joint bleeding, her center recommends prophylaxis.

“Prophylaxis can be very burdensome for patients. You’re talking about IV therapy several times a week, but it’s very helpful for the joint bleeds. Episodic prophylaxis can be very helpful for heavy menstrual bleeding, and we actually have type 2, type 3, and some type 1 patients with bad enough nose bleeds that they end up on prophylaxis,” she said.

Patients with gastrointestinal bleeding are the most challenging to care for, she noted.

“You can put them on factor prophylaxis, but even that isn’t always enough to help some adults with bad GI bleeding, and we’re investigating other options for that,” she said.

Dr. Eikenboom disclosed research support from CSL Behring and honoraria (directed to his institution) for educational activities sponsored by Roche and Celgene. Dr. Flood reported having no conflicts of interest to disclose.

Key clinical point: The 6-year follow-up data from APHINITY trial confirm invasive disease-free survival (IDFS) benefits of adding pertuzumab to adjuvant trastuzumab and chemotherapy in node-positive human epidermal growth factor receptor 2-positive (HER2+) early breast cancer.

Major finding: At 6 years, IDFS was longer in pertuzumab vs. placebo (91% vs. 88%; hazard ratio [HR], 0.76; 95% CI, 0.64-0.91) group, particularly in node-positive cohort (HR, 0.72; 95% CI, 0.59-0.87) but not in node-negative cohort. The overall survival analysis did not reach the required statistical significance (HR, 0.85; P = .17).

Study details: Findings are from a second interim analysis of the phase 3 APHINITY trial including 4,805 patients with node-positive or high-risk node-negative HER2+ breast cancer randomly allocated to receive chemotherapy with either 1 year of trastuzumab + placebo (n = 2,404) or trastuzumab + pertuzumab (n = 2,400) post-surgery.

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd/Genentech. The lead author reported ties with AstraZeneca, Lilly, MSD, Novartis, Pfizer, Debiopharm Group, Odonate Therapeutics, Menarini, Seattle Genetics, Camel-IDS, Immunomedics, Roche/Genentech, Immutep, Radius Health, Synthon, Servier, Oncolytics, and EU Cancer Mission Board. Other investigators declared ties with various pharmaceutical companies including Roche/Genentech.

Source: Piccart M et al. J Clin Oncol. 2021 Feb 4. doi: 10.1200/JCO.20.01204.

Key clinical point: The 6-year follow-up data from APHINITY trial confirm invasive disease-free survival (IDFS) benefits of adding pertuzumab to adjuvant trastuzumab and chemotherapy in node-positive human epidermal growth factor receptor 2-positive (HER2+) early breast cancer.

Major finding: At 6 years, IDFS was longer in pertuzumab vs. placebo (91% vs. 88%; hazard ratio [HR], 0.76; 95% CI, 0.64-0.91) group, particularly in node-positive cohort (HR, 0.72; 95% CI, 0.59-0.87) but not in node-negative cohort. The overall survival analysis did not reach the required statistical significance (HR, 0.85; P = .17).

Study details: Findings are from a second interim analysis of the phase 3 APHINITY trial including 4,805 patients with node-positive or high-risk node-negative HER2+ breast cancer randomly allocated to receive chemotherapy with either 1 year of trastuzumab + placebo (n = 2,404) or trastuzumab + pertuzumab (n = 2,400) post-surgery.

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd/Genentech. The lead author reported ties with AstraZeneca, Lilly, MSD, Novartis, Pfizer, Debiopharm Group, Odonate Therapeutics, Menarini, Seattle Genetics, Camel-IDS, Immunomedics, Roche/Genentech, Immutep, Radius Health, Synthon, Servier, Oncolytics, and EU Cancer Mission Board. Other investigators declared ties with various pharmaceutical companies including Roche/Genentech.

Source: Piccart M et al. J Clin Oncol. 2021 Feb 4. doi: 10.1200/JCO.20.01204.

Key clinical point: The 6-year follow-up data from APHINITY trial confirm invasive disease-free survival (IDFS) benefits of adding pertuzumab to adjuvant trastuzumab and chemotherapy in node-positive human epidermal growth factor receptor 2-positive (HER2+) early breast cancer.

Major finding: At 6 years, IDFS was longer in pertuzumab vs. placebo (91% vs. 88%; hazard ratio [HR], 0.76; 95% CI, 0.64-0.91) group, particularly in node-positive cohort (HR, 0.72; 95% CI, 0.59-0.87) but not in node-negative cohort. The overall survival analysis did not reach the required statistical significance (HR, 0.85; P = .17).

Study details: Findings are from a second interim analysis of the phase 3 APHINITY trial including 4,805 patients with node-positive or high-risk node-negative HER2+ breast cancer randomly allocated to receive chemotherapy with either 1 year of trastuzumab + placebo (n = 2,404) or trastuzumab + pertuzumab (n = 2,400) post-surgery.

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd/Genentech. The lead author reported ties with AstraZeneca, Lilly, MSD, Novartis, Pfizer, Debiopharm Group, Odonate Therapeutics, Menarini, Seattle Genetics, Camel-IDS, Immunomedics, Roche/Genentech, Immutep, Radius Health, Synthon, Servier, Oncolytics, and EU Cancer Mission Board. Other investigators declared ties with various pharmaceutical companies including Roche/Genentech.

Source: Piccart M et al. J Clin Oncol. 2021 Feb 4. doi: 10.1200/JCO.20.01204.

Key clinical point: Pyrotinib+capecitabine significantly improved progression-free survival (PFS) vs. lapatinib+capecitabine with manageable toxicity in women with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) after treatment with trastuzumab and taxanes.

Major finding: Median PFS was significantly longer in the pyrotinib+capecitabine vs. lapatinib+capecitabine group (12.5 vs. 6.8 months; hazard ratio, 0.39; one-sided P less than .0001). Serious adverse events were reported by 10% vs. 8% of patients in the pyrotinib vs. lapatinib group.

Study details: Findings are from an interim analysis of the phase 3 PHOEBE trial including 267 patients with HER2+ MBC previously treated with trastuzumab and taxanes randomly allocated to receive either pyrotinib+capecitabine (n=134) or lapatinib+capecitabine (n=132).

Disclosures: This study was funded by Jiangsu Hengrui Medicine and the National Key R&D Program of China. The lead author reported ties with Hengrui, Novartis, Roche, AstraZeneca, Pfizer, and Eisai. Some other investigators also reported employment or receiving grants and fees from various pharmaceutical companies including Hengrui.

Source: Xu B et al. Lancet Oncol. 2021 Feb 11. doi: 10.1016/S1470-2045(20)30702-6.

Key clinical point: Pyrotinib+capecitabine significantly improved progression-free survival (PFS) vs. lapatinib+capecitabine with manageable toxicity in women with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) after treatment with trastuzumab and taxanes.

Major finding: Median PFS was significantly longer in the pyrotinib+capecitabine vs. lapatinib+capecitabine group (12.5 vs. 6.8 months; hazard ratio, 0.39; one-sided P less than .0001). Serious adverse events were reported by 10% vs. 8% of patients in the pyrotinib vs. lapatinib group.

Study details: Findings are from an interim analysis of the phase 3 PHOEBE trial including 267 patients with HER2+ MBC previously treated with trastuzumab and taxanes randomly allocated to receive either pyrotinib+capecitabine (n=134) or lapatinib+capecitabine (n=132).

Disclosures: This study was funded by Jiangsu Hengrui Medicine and the National Key R&D Program of China. The lead author reported ties with Hengrui, Novartis, Roche, AstraZeneca, Pfizer, and Eisai. Some other investigators also reported employment or receiving grants and fees from various pharmaceutical companies including Hengrui.

Source: Xu B et al. Lancet Oncol. 2021 Feb 11. doi: 10.1016/S1470-2045(20)30702-6.

Key clinical point: Pyrotinib+capecitabine significantly improved progression-free survival (PFS) vs. lapatinib+capecitabine with manageable toxicity in women with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) after treatment with trastuzumab and taxanes.

Major finding: Median PFS was significantly longer in the pyrotinib+capecitabine vs. lapatinib+capecitabine group (12.5 vs. 6.8 months; hazard ratio, 0.39; one-sided P less than .0001). Serious adverse events were reported by 10% vs. 8% of patients in the pyrotinib vs. lapatinib group.

Study details: Findings are from an interim analysis of the phase 3 PHOEBE trial including 267 patients with HER2+ MBC previously treated with trastuzumab and taxanes randomly allocated to receive either pyrotinib+capecitabine (n=134) or lapatinib+capecitabine (n=132).

Disclosures: This study was funded by Jiangsu Hengrui Medicine and the National Key R&D Program of China. The lead author reported ties with Hengrui, Novartis, Roche, AstraZeneca, Pfizer, and Eisai. Some other investigators also reported employment or receiving grants and fees from various pharmaceutical companies including Hengrui.

Source: Xu B et al. Lancet Oncol. 2021 Feb 11. doi: 10.1016/S1470-2045(20)30702-6.

The U.S. Preventive Services Task Force has expanded the criteria for lung cancer screening. The updated final recommendations have lowered the age at which screening starts from 55 to 50 years and have reduced the criterion regarding smoking history from 30 to 20 pack-years.

“This is great news because it means that nearly twice as many people are eligible to be screened, which we hope will allow clinicians to save more lives and help people remain healthy longer,” commented John Wong, MD, chief science officer, vice chair for clinical affairs, and chief of the Division of Clinical Decision Making at USPSTF.

The updated final recommendations were published online on March 9 in JAMA.

The USPSTF recommends annual screening with low-dose CT for adults aged 50-80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.

This updates guidance issued in 2013, which recommended annual screening for lung cancer for adults aged 55-80 years who had a 30 pack-year smoking history and who were either current smokers or had quit within the past 15 years.

The move will nearly double the number of people are now eligible for screening, up to 14.5 million individuals – an increase of 81% (6.4 million adults) from the 2013 recommendations.

The expanded criteria may help increase screening among Black individuals and women. Data show that both groups tend to smoke fewer cigarettes than White men and that Black persons are at higher risk for lung cancer than White persons. In addition, research has shown that about one-third of Black patients with lung cancer were diagnosed before the age of 55 years, which means they would not have been recommended for screening under the previous guidelines.

Uptake has been limited

To date, uptake of lung cancer screening has been very limited, from 6% to 18% of individuals who meet the eligibility criteria.

The new recommendations will open up screening to many more people, but challenges to implementation remain.

“The science is clear that lung cancer screening has the potential to save lives,” Dr. Wong told this news organization. “We recognize that there are existing barriers to screening everyone who is eligible, but clinicians and patients both deserve to know that screening can detect lung cancer early, when treatment has the best chance of being beneficial.”

He added that the hope is that these recommendations will encourage clinicians to examine the barriers to effective lung cancer screening in their communities and to do what they can to improve implementation. “We also hope to encourage patients to have conversations with their clinicians about whether they are eligible for screening and to discuss smoking cessation treatments if they are still smoking,” Dr. Wong added.

In an accompanying editorial, Louise M. Henderson, PhD, M. Patricia Rivera, MD, FCCP, and Ethan Basch, MD, all from the University of North Carolina at Chapel Hill, address some of the current challenges in implementation.

They note that reimbursement for lung cancer screening by Medicare requires submission of data to a Centers for Medicare & Medicaid Services–approved registry, and this can present problems for facilities serving less affluent communities or that have limited resources.

Medicaid coverage is also uneven. As of September 2020, lung cancer screening was covered by 38 Medicaid programs, but not by 9. For three programs, data on coverage were not available.

“With the new recommendations lowering the screening-eligible age to 50 years, many eligible individuals who are uninsured or who are receiving Medicaid and living in states that do not cover screening will have financial barriers to undergo screening,” they write.

In addition, many individuals in at-risk populations lack adequate geographic access to comprehensive lung cancer screening programs.

Expanding eligibility criteria is important, the editorialists point out, but barriers to screening, which include lack of insurance coverage and limited physical access to high-quality screening programs, highlight the complex problems with implementation that need to be addressed.

“A concerted effort to increase the reach of lung cancer screening is needed,” they write. “The 2021 USPSTF recommendation statement represents a leap forward in evidence and offers promise to prevent more cancer deaths and address screening disparities. But the greatest work lies ahead to ensure this promise is actualized.”

Advocacy needed

When approached for comment, Jianjun Zhang, MD, PhD, from the department of thoracic/head and neck medical oncology, University of Texas MD Anderson Cancer Center, Houston, said he supports the new guidelines, and they will lower mortality. “The data are pretty strong overall,” he said in an interview.

Although the uptake of screening is currently very low, he pointed out that, even if uptake remains the same, more lives will be saved because eligibility has been expanded. “More people will be getting screened, so it’s a start,” he said.

Aside from factors such as insurance and access, another problem involves primary care. “Time is very limited in primary care,” he said. “You have about 15 minutes, and it can be really hard to fit everything into a visit. Screening may get left out or may only get a brief mention.”

Advocacy is needed, Dr. Zhang pointed out. “Breast cancer has strong voices and advocacy, and people are more aware of mammography,” he said. “The information is disseminated out into the community. We need the same for lung cancer.”

Dr. Zhang emphasized that, even with the expanded criteria, many individuals will still be missed. “There are other risk factors besides smoking,” he said. “About 10% of lung cancers occur in never-smokers.”

Other risk factors include a family history of lung cancer, exposure to certain materials and chemicals, working in the mining industry, and genetics.

“We will move on to more personalized screening at some point,” he said. “But right now, we can’t make it too complicated for patients and doctors. We need to concentrate on increasing screening rates within these current criteria.”

The updated guidelines have been given a B recommendation, meaning the USPSTF recommends that clinicians provide the service to eligible patients, there is at least fair evidence that this service improves important health outcomes, and benefits outweigh harms.

The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. The original article lists relevant financial relationships of task force members. Dr. Zhang has received grants from Johnson & Johnson and Merck, and adversary/consulting/honoraria fees from AstraZeneca, Bristol-Myers Squibb, GenePlus, Innovent, OrigMed, and Roche.

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

The U.S. Preventive Services Task Force has expanded the criteria for lung cancer screening. The updated final recommendations have lowered the age at which screening starts from 55 to 50 years and have reduced the criterion regarding smoking history from 30 to 20 pack-years.

“This is great news because it means that nearly twice as many people are eligible to be screened, which we hope will allow clinicians to save more lives and help people remain healthy longer,” commented John Wong, MD, chief science officer, vice chair for clinical affairs, and chief of the Division of Clinical Decision Making at USPSTF.

The updated final recommendations were published online on March 9 in JAMA.

The USPSTF recommends annual screening with low-dose CT for adults aged 50-80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.

This updates guidance issued in 2013, which recommended annual screening for lung cancer for adults aged 55-80 years who had a 30 pack-year smoking history and who were either current smokers or had quit within the past 15 years.

The move will nearly double the number of people are now eligible for screening, up to 14.5 million individuals – an increase of 81% (6.4 million adults) from the 2013 recommendations.

The expanded criteria may help increase screening among Black individuals and women. Data show that both groups tend to smoke fewer cigarettes than White men and that Black persons are at higher risk for lung cancer than White persons. In addition, research has shown that about one-third of Black patients with lung cancer were diagnosed before the age of 55 years, which means they would not have been recommended for screening under the previous guidelines.

Uptake has been limited

To date, uptake of lung cancer screening has been very limited, from 6% to 18% of individuals who meet the eligibility criteria.

The new recommendations will open up screening to many more people, but challenges to implementation remain.

“The science is clear that lung cancer screening has the potential to save lives,” Dr. Wong told this news organization. “We recognize that there are existing barriers to screening everyone who is eligible, but clinicians and patients both deserve to know that screening can detect lung cancer early, when treatment has the best chance of being beneficial.”

He added that the hope is that these recommendations will encourage clinicians to examine the barriers to effective lung cancer screening in their communities and to do what they can to improve implementation. “We also hope to encourage patients to have conversations with their clinicians about whether they are eligible for screening and to discuss smoking cessation treatments if they are still smoking,” Dr. Wong added.

In an accompanying editorial, Louise M. Henderson, PhD, M. Patricia Rivera, MD, FCCP, and Ethan Basch, MD, all from the University of North Carolina at Chapel Hill, address some of the current challenges in implementation.

They note that reimbursement for lung cancer screening by Medicare requires submission of data to a Centers for Medicare & Medicaid Services–approved registry, and this can present problems for facilities serving less affluent communities or that have limited resources.

Medicaid coverage is also uneven. As of September 2020, lung cancer screening was covered by 38 Medicaid programs, but not by 9. For three programs, data on coverage were not available.

“With the new recommendations lowering the screening-eligible age to 50 years, many eligible individuals who are uninsured or who are receiving Medicaid and living in states that do not cover screening will have financial barriers to undergo screening,” they write.

In addition, many individuals in at-risk populations lack adequate geographic access to comprehensive lung cancer screening programs.

Expanding eligibility criteria is important, the editorialists point out, but barriers to screening, which include lack of insurance coverage and limited physical access to high-quality screening programs, highlight the complex problems with implementation that need to be addressed.

“A concerted effort to increase the reach of lung cancer screening is needed,” they write. “The 2021 USPSTF recommendation statement represents a leap forward in evidence and offers promise to prevent more cancer deaths and address screening disparities. But the greatest work lies ahead to ensure this promise is actualized.”

Advocacy needed

When approached for comment, Jianjun Zhang, MD, PhD, from the department of thoracic/head and neck medical oncology, University of Texas MD Anderson Cancer Center, Houston, said he supports the new guidelines, and they will lower mortality. “The data are pretty strong overall,” he said in an interview.

Although the uptake of screening is currently very low, he pointed out that, even if uptake remains the same, more lives will be saved because eligibility has been expanded. “More people will be getting screened, so it’s a start,” he said.

Aside from factors such as insurance and access, another problem involves primary care. “Time is very limited in primary care,” he said. “You have about 15 minutes, and it can be really hard to fit everything into a visit. Screening may get left out or may only get a brief mention.”

Advocacy is needed, Dr. Zhang pointed out. “Breast cancer has strong voices and advocacy, and people are more aware of mammography,” he said. “The information is disseminated out into the community. We need the same for lung cancer.”

Dr. Zhang emphasized that, even with the expanded criteria, many individuals will still be missed. “There are other risk factors besides smoking,” he said. “About 10% of lung cancers occur in never-smokers.”

Other risk factors include a family history of lung cancer, exposure to certain materials and chemicals, working in the mining industry, and genetics.

“We will move on to more personalized screening at some point,” he said. “But right now, we can’t make it too complicated for patients and doctors. We need to concentrate on increasing screening rates within these current criteria.”

The updated guidelines have been given a B recommendation, meaning the USPSTF recommends that clinicians provide the service to eligible patients, there is at least fair evidence that this service improves important health outcomes, and benefits outweigh harms.

The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. The original article lists relevant financial relationships of task force members. Dr. Zhang has received grants from Johnson & Johnson and Merck, and adversary/consulting/honoraria fees from AstraZeneca, Bristol-Myers Squibb, GenePlus, Innovent, OrigMed, and Roche.

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

The U.S. Preventive Services Task Force has expanded the criteria for lung cancer screening. The updated final recommendations have lowered the age at which screening starts from 55 to 50 years and have reduced the criterion regarding smoking history from 30 to 20 pack-years.

“This is great news because it means that nearly twice as many people are eligible to be screened, which we hope will allow clinicians to save more lives and help people remain healthy longer,” commented John Wong, MD, chief science officer, vice chair for clinical affairs, and chief of the Division of Clinical Decision Making at USPSTF.

The updated final recommendations were published online on March 9 in JAMA.

The USPSTF recommends annual screening with low-dose CT for adults aged 50-80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.

This updates guidance issued in 2013, which recommended annual screening for lung cancer for adults aged 55-80 years who had a 30 pack-year smoking history and who were either current smokers or had quit within the past 15 years.

The move will nearly double the number of people are now eligible for screening, up to 14.5 million individuals – an increase of 81% (6.4 million adults) from the 2013 recommendations.

The expanded criteria may help increase screening among Black individuals and women. Data show that both groups tend to smoke fewer cigarettes than White men and that Black persons are at higher risk for lung cancer than White persons. In addition, research has shown that about one-third of Black patients with lung cancer were diagnosed before the age of 55 years, which means they would not have been recommended for screening under the previous guidelines.

Uptake has been limited

To date, uptake of lung cancer screening has been very limited, from 6% to 18% of individuals who meet the eligibility criteria.

The new recommendations will open up screening to many more people, but challenges to implementation remain.

“The science is clear that lung cancer screening has the potential to save lives,” Dr. Wong told this news organization. “We recognize that there are existing barriers to screening everyone who is eligible, but clinicians and patients both deserve to know that screening can detect lung cancer early, when treatment has the best chance of being beneficial.”

He added that the hope is that these recommendations will encourage clinicians to examine the barriers to effective lung cancer screening in their communities and to do what they can to improve implementation. “We also hope to encourage patients to have conversations with their clinicians about whether they are eligible for screening and to discuss smoking cessation treatments if they are still smoking,” Dr. Wong added.

In an accompanying editorial, Louise M. Henderson, PhD, M. Patricia Rivera, MD, FCCP, and Ethan Basch, MD, all from the University of North Carolina at Chapel Hill, address some of the current challenges in implementation.

They note that reimbursement for lung cancer screening by Medicare requires submission of data to a Centers for Medicare & Medicaid Services–approved registry, and this can present problems for facilities serving less affluent communities or that have limited resources.

Medicaid coverage is also uneven. As of September 2020, lung cancer screening was covered by 38 Medicaid programs, but not by 9. For three programs, data on coverage were not available.

“With the new recommendations lowering the screening-eligible age to 50 years, many eligible individuals who are uninsured or who are receiving Medicaid and living in states that do not cover screening will have financial barriers to undergo screening,” they write.

In addition, many individuals in at-risk populations lack adequate geographic access to comprehensive lung cancer screening programs.

Expanding eligibility criteria is important, the editorialists point out, but barriers to screening, which include lack of insurance coverage and limited physical access to high-quality screening programs, highlight the complex problems with implementation that need to be addressed.

“A concerted effort to increase the reach of lung cancer screening is needed,” they write. “The 2021 USPSTF recommendation statement represents a leap forward in evidence and offers promise to prevent more cancer deaths and address screening disparities. But the greatest work lies ahead to ensure this promise is actualized.”

Advocacy needed

When approached for comment, Jianjun Zhang, MD, PhD, from the department of thoracic/head and neck medical oncology, University of Texas MD Anderson Cancer Center, Houston, said he supports the new guidelines, and they will lower mortality. “The data are pretty strong overall,” he said in an interview.

Although the uptake of screening is currently very low, he pointed out that, even if uptake remains the same, more lives will be saved because eligibility has been expanded. “More people will be getting screened, so it’s a start,” he said.

Aside from factors such as insurance and access, another problem involves primary care. “Time is very limited in primary care,” he said. “You have about 15 minutes, and it can be really hard to fit everything into a visit. Screening may get left out or may only get a brief mention.”

Advocacy is needed, Dr. Zhang pointed out. “Breast cancer has strong voices and advocacy, and people are more aware of mammography,” he said. “The information is disseminated out into the community. We need the same for lung cancer.”

Dr. Zhang emphasized that, even with the expanded criteria, many individuals will still be missed. “There are other risk factors besides smoking,” he said. “About 10% of lung cancers occur in never-smokers.”

Other risk factors include a family history of lung cancer, exposure to certain materials and chemicals, working in the mining industry, and genetics.

“We will move on to more personalized screening at some point,” he said. “But right now, we can’t make it too complicated for patients and doctors. We need to concentrate on increasing screening rates within these current criteria.”

The updated guidelines have been given a B recommendation, meaning the USPSTF recommends that clinicians provide the service to eligible patients, there is at least fair evidence that this service improves important health outcomes, and benefits outweigh harms.

The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. The original article lists relevant financial relationships of task force members. Dr. Zhang has received grants from Johnson & Johnson and Merck, and adversary/consulting/honoraria fees from AstraZeneca, Bristol-Myers Squibb, GenePlus, Innovent, OrigMed, and Roche.

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

Officials have previously linked being overweight or obese to a greater risk for more severe COVID-19. A report today from the U.S. Centers for Disease Control and Prevention adds numbers and some nuance to the association.

Data from nearly 150,000 U.S. adults hospitalized with COVID-19 nationwide indicate that risk for more severe disease outcomes increases along with body mass index (BMI). The risk of COVID-19–related hospitalization and death associated with obesity was particularly high among people younger than 65.

“As clinicians develop care plans for COVID-19 patients, they should consider the risk for severe outcomes in patients with higher BMIs, especially for those with severe obesity,” the researchers note. They add that their findings suggest “progressively intensive management of COVID-19 might be needed for patients with more severe obesity.”

People with COVID-19 close to the border between a healthy and overweight BMI – from 23.7 kg/m² to 25.9 kg/m² – had the lowest risks for adverse outcomes.

The study was published online today in Morbidity and Mortality Weekly Report.
 

Greater need for critical care

The risk of ICU admission was particularly associated with severe obesity. For example, those with a BMI in the 40-44.9 kg/m² category had a 6% increased risk, which jumped to 16% higher among those with a BMI of 45 or greater.

Compared to people with a healthy BMI, the need for invasive mechanical ventilation was 12% more likely among overweight adults with a BMI of 25-29.2. The risked jumped to 108% greater among the most obese people, those with a BMI of 45 or greater, lead CDC researcher Lyudmyla Kompaniyets, PhD, and colleagues reported.

Moreover, the risks for hospitalization and death increased in a dose-response relationship with obesity.

For example, risks of being hospitalized were 7% greater for adults with a BMI between 30 and 34.9 and climbed to 33% greater for those with a BMI of 45. Risks were calculated as adjusted relative risks compared with people with a healthy BMI between 18.5 and 24.9.

Interestingly, being underweight was associated with elevated risk for COVID-19 hospitalization as well. For example, people with a BMI of less than 18.5 had a 20% greater chance of admission vs. people in the healthy BMI range. Unknown underlying medical conditions or issues related to nutrition or immune function could be contributing factors, the researchers note.
 

Elevated risk of dying

The risk of death in adults with obesity ranged from 8% higher in the 30-34.9 range up to 61% greater for those with a BMI of 45.

Chronic inflammation or impaired lung function from excess weight are possible reasons that higher BMI imparts greater risk, the researchers note.

The CDC researchers evaluated 148,494 adults from 238 hospitals participating in PHD-SR database. Because the study was limited to people hospitalized with COVID-19, the findings may not apply to all adults with COVID-19.

Another potential limitation is that investigators were unable to calculate BMI for all patients in the database because about 28% of participating hospitals did not report height and weight.

The study authors had no relevant financial relationships to disclose. 

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

Officials have previously linked being overweight or obese to a greater risk for more severe COVID-19. A report today from the U.S. Centers for Disease Control and Prevention adds numbers and some nuance to the association.

Data from nearly 150,000 U.S. adults hospitalized with COVID-19 nationwide indicate that risk for more severe disease outcomes increases along with body mass index (BMI). The risk of COVID-19–related hospitalization and death associated with obesity was particularly high among people younger than 65.

“As clinicians develop care plans for COVID-19 patients, they should consider the risk for severe outcomes in patients with higher BMIs, especially for those with severe obesity,” the researchers note. They add that their findings suggest “progressively intensive management of COVID-19 might be needed for patients with more severe obesity.”

People with COVID-19 close to the border between a healthy and overweight BMI – from 23.7 kg/m² to 25.9 kg/m² – had the lowest risks for adverse outcomes.

The study was published online today in Morbidity and Mortality Weekly Report.
 

Greater need for critical care

The risk of ICU admission was particularly associated with severe obesity. For example, those with a BMI in the 40-44.9 kg/m² category had a 6% increased risk, which jumped to 16% higher among those with a BMI of 45 or greater.

Compared to people with a healthy BMI, the need for invasive mechanical ventilation was 12% more likely among overweight adults with a BMI of 25-29.2. The risked jumped to 108% greater among the most obese people, those with a BMI of 45 or greater, lead CDC researcher Lyudmyla Kompaniyets, PhD, and colleagues reported.

Moreover, the risks for hospitalization and death increased in a dose-response relationship with obesity.

For example, risks of being hospitalized were 7% greater for adults with a BMI between 30 and 34.9 and climbed to 33% greater for those with a BMI of 45. Risks were calculated as adjusted relative risks compared with people with a healthy BMI between 18.5 and 24.9.

Interestingly, being underweight was associated with elevated risk for COVID-19 hospitalization as well. For example, people with a BMI of less than 18.5 had a 20% greater chance of admission vs. people in the healthy BMI range. Unknown underlying medical conditions or issues related to nutrition or immune function could be contributing factors, the researchers note.
 

Elevated risk of dying

The risk of death in adults with obesity ranged from 8% higher in the 30-34.9 range up to 61% greater for those with a BMI of 45.

Chronic inflammation or impaired lung function from excess weight are possible reasons that higher BMI imparts greater risk, the researchers note.

The CDC researchers evaluated 148,494 adults from 238 hospitals participating in PHD-SR database. Because the study was limited to people hospitalized with COVID-19, the findings may not apply to all adults with COVID-19.

Another potential limitation is that investigators were unable to calculate BMI for all patients in the database because about 28% of participating hospitals did not report height and weight.

The study authors had no relevant financial relationships to disclose. 

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

Officials have previously linked being overweight or obese to a greater risk for more severe COVID-19. A report today from the U.S. Centers for Disease Control and Prevention adds numbers and some nuance to the association.

Data from nearly 150,000 U.S. adults hospitalized with COVID-19 nationwide indicate that risk for more severe disease outcomes increases along with body mass index (BMI). The risk of COVID-19–related hospitalization and death associated with obesity was particularly high among people younger than 65.

“As clinicians develop care plans for COVID-19 patients, they should consider the risk for severe outcomes in patients with higher BMIs, especially for those with severe obesity,” the researchers note. They add that their findings suggest “progressively intensive management of COVID-19 might be needed for patients with more severe obesity.”

People with COVID-19 close to the border between a healthy and overweight BMI – from 23.7 kg/m² to 25.9 kg/m² – had the lowest risks for adverse outcomes.

The study was published online today in Morbidity and Mortality Weekly Report.
 

Greater need for critical care

The risk of ICU admission was particularly associated with severe obesity. For example, those with a BMI in the 40-44.9 kg/m² category had a 6% increased risk, which jumped to 16% higher among those with a BMI of 45 or greater.

Compared to people with a healthy BMI, the need for invasive mechanical ventilation was 12% more likely among overweight adults with a BMI of 25-29.2. The risked jumped to 108% greater among the most obese people, those with a BMI of 45 or greater, lead CDC researcher Lyudmyla Kompaniyets, PhD, and colleagues reported.

Moreover, the risks for hospitalization and death increased in a dose-response relationship with obesity.

For example, risks of being hospitalized were 7% greater for adults with a BMI between 30 and 34.9 and climbed to 33% greater for those with a BMI of 45. Risks were calculated as adjusted relative risks compared with people with a healthy BMI between 18.5 and 24.9.

Interestingly, being underweight was associated with elevated risk for COVID-19 hospitalization as well. For example, people with a BMI of less than 18.5 had a 20% greater chance of admission vs. people in the healthy BMI range. Unknown underlying medical conditions or issues related to nutrition or immune function could be contributing factors, the researchers note.
 

Elevated risk of dying

The risk of death in adults with obesity ranged from 8% higher in the 30-34.9 range up to 61% greater for those with a BMI of 45.

Chronic inflammation or impaired lung function from excess weight are possible reasons that higher BMI imparts greater risk, the researchers note.

The CDC researchers evaluated 148,494 adults from 238 hospitals participating in PHD-SR database. Because the study was limited to people hospitalized with COVID-19, the findings may not apply to all adults with COVID-19.

Another potential limitation is that investigators were unable to calculate BMI for all patients in the database because about 28% of participating hospitals did not report height and weight.

The study authors had no relevant financial relationships to disclose. 

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