Breast Cancer

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Investigators presented results of the phase 3 IMpassion130 earlier this year demonstrating, for the first time, that a combination of an immune checkpoint inhibitor and a taxane provided significant clinical benefit to patients with advanced triple-negative breast cancer. However, the benefit was seen only in patients positive for programmed death-ligand 1 (PD-L1), the investigators reported at the annual congress of the European Society for Medical Oncology.

In the trial, 902 patients with untreated metastatic triple-negative breast cancer (mTNBC) were randomly assigned to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-paclitaxel. In an interim analysis, although there was no significant difference in median overall survival among all participants, atezolizumab was associated with a 38% improvement in median overall survival among patients with PD-L1–positive disease.

Additional analyses of the efficacy within immune biomarker subgroups in IMpassion130, including efficacy by BRCA status, will be presented at the upcoming 2018 San Antonio Breast Cancer Symposium, to be held Dec. 4-8 in San Antonio.

Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology, co-leader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center, will present the additional analyses on Wednesday, Dec. 5th at 9:30 a.m. CST.






 

Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.

In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.

“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.

Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.

The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.

The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.

The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.

Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.

One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.

Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.

“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”

The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”

However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.

“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.

The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.

SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
 

Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.

In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.

“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.

Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.

The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.

The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.

The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.

Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.

One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.

Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.

“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”

The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”

However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.

“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.

The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.

SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
 

Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.

In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.

“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.

Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.

The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.

The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.

The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.

Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.

One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.

Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.

“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”

The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”

However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.

“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.

The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.

SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
 

BOSTON – For women undergoing nipple-sparing mastectomy, advanced age and neoadjuvant chemotherapy are not associated with increased postoperative complications, results of recent studies suggest.

Andrew D. Bowser/MDedge News

The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.

“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.

The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.

“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.

Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.

The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.

Andrew D. Bowser/MDedge News

SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018

BOSTON – For women undergoing nipple-sparing mastectomy, advanced age and neoadjuvant chemotherapy are not associated with increased postoperative complications, results of recent studies suggest.

Andrew D. Bowser/MDedge News

The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.

“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.

The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.

“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.

Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.

The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.

Andrew D. Bowser/MDedge News

SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018

BOSTON – For women undergoing nipple-sparing mastectomy, advanced age and neoadjuvant chemotherapy are not associated with increased postoperative complications, results of recent studies suggest.

Andrew D. Bowser/MDedge News

The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.

“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.

The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.

“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.

Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.

The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.

Andrew D. Bowser/MDedge News

SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018

The Food and Drug Administration has approved a second biosimilar to pegfilgrastim (Neulasta) to decrease the chance of infection in patients with nonmyeloid cancer who are receiving myelosuppressive chemotherapy and are at risk of febrile neutropenia.

Approval of pegfilgrastim-cbqv, previously known as CHS-1701, was based on analyses establishing biosimilarity, including pharmacokinetic, pharmacodynamic, and immunogenicity studies. Clinical trial results were presented at the 2017 ASCO Annual Meeting.

The most common adverse reactions with pegfilgrastim-cbqv are bone pain and pain in extremities.

The FDA approved the first pegfilgrastim biosimilar, pegfilgrastim-jmdb (Fulphila) in June.

Pegfilgrastim-cbqv will be marketed as Udenyca by Coherus BioSciences.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” Barbara Finck, MD, chief medical officer of Coherus BioSciences, said in a press release.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

Coherus BioSciences plans to provide details about pricing and the launch of pegfilgrastim-cbqv during an earnings call on Nov. 8.

The Food and Drug Administration has approved a second biosimilar to pegfilgrastim (Neulasta) to decrease the chance of infection in patients with nonmyeloid cancer who are receiving myelosuppressive chemotherapy and are at risk of febrile neutropenia.

Approval of pegfilgrastim-cbqv, previously known as CHS-1701, was based on analyses establishing biosimilarity, including pharmacokinetic, pharmacodynamic, and immunogenicity studies. Clinical trial results were presented at the 2017 ASCO Annual Meeting.

The most common adverse reactions with pegfilgrastim-cbqv are bone pain and pain in extremities.

The FDA approved the first pegfilgrastim biosimilar, pegfilgrastim-jmdb (Fulphila) in June.

Pegfilgrastim-cbqv will be marketed as Udenyca by Coherus BioSciences.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” Barbara Finck, MD, chief medical officer of Coherus BioSciences, said in a press release.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

Coherus BioSciences plans to provide details about pricing and the launch of pegfilgrastim-cbqv during an earnings call on Nov. 8.

The Food and Drug Administration has approved a second biosimilar to pegfilgrastim (Neulasta) to decrease the chance of infection in patients with nonmyeloid cancer who are receiving myelosuppressive chemotherapy and are at risk of febrile neutropenia.

Approval of pegfilgrastim-cbqv, previously known as CHS-1701, was based on analyses establishing biosimilarity, including pharmacokinetic, pharmacodynamic, and immunogenicity studies. Clinical trial results were presented at the 2017 ASCO Annual Meeting.

The most common adverse reactions with pegfilgrastim-cbqv are bone pain and pain in extremities.

The FDA approved the first pegfilgrastim biosimilar, pegfilgrastim-jmdb (Fulphila) in June.

Pegfilgrastim-cbqv will be marketed as Udenyca by Coherus BioSciences.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” Barbara Finck, MD, chief medical officer of Coherus BioSciences, said in a press release.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

Coherus BioSciences plans to provide details about pricing and the launch of pegfilgrastim-cbqv during an earnings call on Nov. 8.

American Indian/Alaska Native (AI/AN) women face the same barriers as all low-income minority women face in accessing preventive care, but according to researchers from Rutgers University in New Jersey and University of Arizona, they also face “unique challenges and circumstances.” The researchers reviewed 18 studies to find out more about facilitators of, and barriers to, breast cancer screening.

Low-income women are more likely to be diagnosed at a later stage and to die of breast cancer, one study found. The factors are well known: cost, lack of a usual source of care, lack of insurance, distance from a facility, and lack of transportation.

However, the researchers of the meta-analysis say, “compounding these barriers,” AI/AN women expressed the belief that preventive care is not a priority, especially when it is their own preventive care. Moreover, some barriers that might be unique to the AI/AN women included concern with “manifest destiny”: the assumption that thinking or talking about breast cancer can cause it, for instance. One study examined “traditionality” and found women who could be seen as more traditional, defining themselves as living an “Indian way of life,” were less likely to be current with screening. Other women expressed mistrust in the technology of screening or spoke about perception of discrimination in the health care system.

Although this population has access to screening through IHS facilities, women who also have insurance (typically Medicaid) are more likely to get screened. Women in rural areas who lived near an IHS facility were more likely than were urban women to get mammograms. The researchers suggest this could be because rural women are more likely to be isolated from other mammogram facilities. Too, the IHS is “chronically underfunded,” the researchers note, likely a cause of the health disparities and limiting scope of services.

Their review made clear that efforts to intervene with AI/AN women to increase breast cancer screening have been limited, the researchers say. The intervention studies they reviewed “were not successful in improving screening rates or adherence.” The qualitative studies, on the other hand, suggest that women may be more responsive to locally supportive, targeted, and culturally appropriate interventions that respect traditionality yet encourage trust in the medical system.

American Indian/Alaska Native (AI/AN) women face the same barriers as all low-income minority women face in accessing preventive care, but according to researchers from Rutgers University in New Jersey and University of Arizona, they also face “unique challenges and circumstances.” The researchers reviewed 18 studies to find out more about facilitators of, and barriers to, breast cancer screening.

Low-income women are more likely to be diagnosed at a later stage and to die of breast cancer, one study found. The factors are well known: cost, lack of a usual source of care, lack of insurance, distance from a facility, and lack of transportation.

However, the researchers of the meta-analysis say, “compounding these barriers,” AI/AN women expressed the belief that preventive care is not a priority, especially when it is their own preventive care. Moreover, some barriers that might be unique to the AI/AN women included concern with “manifest destiny”: the assumption that thinking or talking about breast cancer can cause it, for instance. One study examined “traditionality” and found women who could be seen as more traditional, defining themselves as living an “Indian way of life,” were less likely to be current with screening. Other women expressed mistrust in the technology of screening or spoke about perception of discrimination in the health care system.

Although this population has access to screening through IHS facilities, women who also have insurance (typically Medicaid) are more likely to get screened. Women in rural areas who lived near an IHS facility were more likely than were urban women to get mammograms. The researchers suggest this could be because rural women are more likely to be isolated from other mammogram facilities. Too, the IHS is “chronically underfunded,” the researchers note, likely a cause of the health disparities and limiting scope of services.

Their review made clear that efforts to intervene with AI/AN women to increase breast cancer screening have been limited, the researchers say. The intervention studies they reviewed “were not successful in improving screening rates or adherence.” The qualitative studies, on the other hand, suggest that women may be more responsive to locally supportive, targeted, and culturally appropriate interventions that respect traditionality yet encourage trust in the medical system.

American Indian/Alaska Native (AI/AN) women face the same barriers as all low-income minority women face in accessing preventive care, but according to researchers from Rutgers University in New Jersey and University of Arizona, they also face “unique challenges and circumstances.” The researchers reviewed 18 studies to find out more about facilitators of, and barriers to, breast cancer screening.

Low-income women are more likely to be diagnosed at a later stage and to die of breast cancer, one study found. The factors are well known: cost, lack of a usual source of care, lack of insurance, distance from a facility, and lack of transportation.

However, the researchers of the meta-analysis say, “compounding these barriers,” AI/AN women expressed the belief that preventive care is not a priority, especially when it is their own preventive care. Moreover, some barriers that might be unique to the AI/AN women included concern with “manifest destiny”: the assumption that thinking or talking about breast cancer can cause it, for instance. One study examined “traditionality” and found women who could be seen as more traditional, defining themselves as living an “Indian way of life,” were less likely to be current with screening. Other women expressed mistrust in the technology of screening or spoke about perception of discrimination in the health care system.

Although this population has access to screening through IHS facilities, women who also have insurance (typically Medicaid) are more likely to get screened. Women in rural areas who lived near an IHS facility were more likely than were urban women to get mammograms. The researchers suggest this could be because rural women are more likely to be isolated from other mammogram facilities. Too, the IHS is “chronically underfunded,” the researchers note, likely a cause of the health disparities and limiting scope of services.

Their review made clear that efforts to intervene with AI/AN women to increase breast cancer screening have been limited, the researchers say. The intervention studies they reviewed “were not successful in improving screening rates or adherence.” The qualitative studies, on the other hand, suggest that women may be more responsive to locally supportive, targeted, and culturally appropriate interventions that respect traditionality yet encourage trust in the medical system.

Moderate application of topical therapies directly prior to radiotherapy (RT) treatment sessions may be safe and might exhibit minimal effects on delivered treatment dose, investigators report.

The researchers found that although avoiding topical agents prior to radiation treatments was widespread, preclinical data indicate that there is no difference in the radiation dose on the skin with or without a 1- to 2-mm-thick layer of topical agent.

In an online survey, which queried 133 patients and 108 clinicians in relation to existing practices surrounding topical agent use, 83.4% of patients were informed to discontinue application of topical therapies directly before RT treatment sessions. In addition, 54.1% were told to clean and remove any enduring topical agents before treatment. Among clinicians, 91.4% reported to have received or given advice to stop application of topicals before obtaining RT treatment, Brian C. Baumann, MD, and his associates reported in JAMA Oncology.

However, in a preclinical study using a mouse- and tissue-equivalent phantom model to determine the dosimetric effects of concomitant topical agent use with daily RT treatments, Dr. Baumann, of Washington University in St. Louis, and his colleagues determined that when a topical agent was given prior to RT at a thickness below 2 mm, no changes were seen in radiation treatment dose, irrespective of depth, photon and electron energy level, or beam angle.

However, a proportionally thicker covering (3 mm or more) caused a bolus effect at the surface, which resulted in electron dose increases of 2%-5%, and photon increases of 15%-35%, when compared with controls.

Investigators measured radiation dose and photon beam intensity at various surface depths after applying two commonly used topical therapies, a healing ointment of 41% petrolatum or silver sulfadiazine cream 1%. The agents were administered using a thick (1-2 mm) application and proportionally thicker (3 mm or more) covering.

“Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence,” the investigators wrote. However, the findings do suggest that “applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided,” they said.

The authors reported that the study was funded by development funds from the University of Pennsylvania, Philadelphia. One of the coauthors, James M. Metz, MD, disclosed service on advisory boards for Ion Beam Applications and Varian Medical Systems for proton therapy; however, these roles were not relevant to this study.
 

SOURCE: Baumann BC et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4292.

Moderate application of topical therapies directly prior to radiotherapy (RT) treatment sessions may be safe and might exhibit minimal effects on delivered treatment dose, investigators report.

The researchers found that although avoiding topical agents prior to radiation treatments was widespread, preclinical data indicate that there is no difference in the radiation dose on the skin with or without a 1- to 2-mm-thick layer of topical agent.

In an online survey, which queried 133 patients and 108 clinicians in relation to existing practices surrounding topical agent use, 83.4% of patients were informed to discontinue application of topical therapies directly before RT treatment sessions. In addition, 54.1% were told to clean and remove any enduring topical agents before treatment. Among clinicians, 91.4% reported to have received or given advice to stop application of topicals before obtaining RT treatment, Brian C. Baumann, MD, and his associates reported in JAMA Oncology.

However, in a preclinical study using a mouse- and tissue-equivalent phantom model to determine the dosimetric effects of concomitant topical agent use with daily RT treatments, Dr. Baumann, of Washington University in St. Louis, and his colleagues determined that when a topical agent was given prior to RT at a thickness below 2 mm, no changes were seen in radiation treatment dose, irrespective of depth, photon and electron energy level, or beam angle.

However, a proportionally thicker covering (3 mm or more) caused a bolus effect at the surface, which resulted in electron dose increases of 2%-5%, and photon increases of 15%-35%, when compared with controls.

Investigators measured radiation dose and photon beam intensity at various surface depths after applying two commonly used topical therapies, a healing ointment of 41% petrolatum or silver sulfadiazine cream 1%. The agents were administered using a thick (1-2 mm) application and proportionally thicker (3 mm or more) covering.

“Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence,” the investigators wrote. However, the findings do suggest that “applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided,” they said.

The authors reported that the study was funded by development funds from the University of Pennsylvania, Philadelphia. One of the coauthors, James M. Metz, MD, disclosed service on advisory boards for Ion Beam Applications and Varian Medical Systems for proton therapy; however, these roles were not relevant to this study.
 

SOURCE: Baumann BC et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4292.

Moderate application of topical therapies directly prior to radiotherapy (RT) treatment sessions may be safe and might exhibit minimal effects on delivered treatment dose, investigators report.

The researchers found that although avoiding topical agents prior to radiation treatments was widespread, preclinical data indicate that there is no difference in the radiation dose on the skin with or without a 1- to 2-mm-thick layer of topical agent.

In an online survey, which queried 133 patients and 108 clinicians in relation to existing practices surrounding topical agent use, 83.4% of patients were informed to discontinue application of topical therapies directly before RT treatment sessions. In addition, 54.1% were told to clean and remove any enduring topical agents before treatment. Among clinicians, 91.4% reported to have received or given advice to stop application of topicals before obtaining RT treatment, Brian C. Baumann, MD, and his associates reported in JAMA Oncology.

However, in a preclinical study using a mouse- and tissue-equivalent phantom model to determine the dosimetric effects of concomitant topical agent use with daily RT treatments, Dr. Baumann, of Washington University in St. Louis, and his colleagues determined that when a topical agent was given prior to RT at a thickness below 2 mm, no changes were seen in radiation treatment dose, irrespective of depth, photon and electron energy level, or beam angle.

However, a proportionally thicker covering (3 mm or more) caused a bolus effect at the surface, which resulted in electron dose increases of 2%-5%, and photon increases of 15%-35%, when compared with controls.

Investigators measured radiation dose and photon beam intensity at various surface depths after applying two commonly used topical therapies, a healing ointment of 41% petrolatum or silver sulfadiazine cream 1%. The agents were administered using a thick (1-2 mm) application and proportionally thicker (3 mm or more) covering.

“Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence,” the investigators wrote. However, the findings do suggest that “applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided,” they said.

The authors reported that the study was funded by development funds from the University of Pennsylvania, Philadelphia. One of the coauthors, James M. Metz, MD, disclosed service on advisory boards for Ion Beam Applications and Varian Medical Systems for proton therapy; however, these roles were not relevant to this study.
 

SOURCE: Baumann BC et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4292.

Researchers from general obstetrics and gynecology (ob.gyn.) practices in New York and Connecticut have shown that a 4-week intervention may improve genetic screening and testing rates for hereditary breast and ovarian cancers (HBOC).

Genetic screening and testing can reduce the morbidity and mortality from breast, ovarian, and endometrial cancers through prevention and early detection. Mark S. DeFrancesco, MD, of Westwood Women’s Health, Waterbury, Conn., and his colleagues reported that, in spite of the American College of Obstetricians and Gynecologists’ recommendation for ob.gyns. to regularly screen, counsel, and refer accordingly for HBOC (Obstet Gynecol. 2015;125:153843), the “incorporation of hereditary cancer risk assessment and testing remains underutilized in the [ob.gyn.] setting.” The authors have addressed this issue in their own practice with promising results and important caveats (Obstet Gynecol 2018;132:1121-9).

The intervention included a process evaluation, improvements to patient work flow, and training of providers by genetic counselors and engineering personnel from the testing laboratory (Myriad Genetics), which provided support for the study. Patients in the study completed a family history questionnaire and, those meeting National Comprehensive Cancer Center Network criteria for genetic testing, were given pretest counseling and offered testing on the same day or referral for testing within 2 weeks.

Of the 3,811 women who completed the questionnaire, 24% (906) met NCCN criteria, 90% of whom were offered testing. However, only 52% (165) of patients who agreed to testing underwent genetic evaluation. This included 70% of patients who were offered same-day testing and 35% of patients who were offered a referral appointment for testing.

Conversations about HBOC and genetic testing can be complicated and may not be a patient’s initial priority. The authors should be commended for identifying the vast majority of high-risk patients. However, only half of patients meeting criteria completed testing and 10% who should have been offered testing were not – numbers still well below target.

Incorporation of family history questionnaires should become commonplace in the generalist’s office and optimizing EHRs may be an opportunity for rapid risk interpretation. As the success of same-day genetic testing was striking, opportunities for partnerships with insurance companies and private laboratories are likely needed to make this a more feasible option. Lastly, assessing women’s knowledge and attitudes around genetic testing could help to more specifically address barriers to testing in future interventions.

Improving genetic screening and testing completion rates requires a coordinated effort. Using tools and applications to optimize convenience (same-day testing, telemedicine) and simplification (electronic screening platforms), we can strive to appropriately detect all women at high risk for hereditary breast and ovarian cancers.

Michelle Lightfoot is a gynecologic oncology fellow at the Ohio State University in Columbus. She has no relevant financial disclosures. Email her at [email protected].

Researchers from general obstetrics and gynecology (ob.gyn.) practices in New York and Connecticut have shown that a 4-week intervention may improve genetic screening and testing rates for hereditary breast and ovarian cancers (HBOC).

Genetic screening and testing can reduce the morbidity and mortality from breast, ovarian, and endometrial cancers through prevention and early detection. Mark S. DeFrancesco, MD, of Westwood Women’s Health, Waterbury, Conn., and his colleagues reported that, in spite of the American College of Obstetricians and Gynecologists’ recommendation for ob.gyns. to regularly screen, counsel, and refer accordingly for HBOC (Obstet Gynecol. 2015;125:153843), the “incorporation of hereditary cancer risk assessment and testing remains underutilized in the [ob.gyn.] setting.” The authors have addressed this issue in their own practice with promising results and important caveats (Obstet Gynecol 2018;132:1121-9).

The intervention included a process evaluation, improvements to patient work flow, and training of providers by genetic counselors and engineering personnel from the testing laboratory (Myriad Genetics), which provided support for the study. Patients in the study completed a family history questionnaire and, those meeting National Comprehensive Cancer Center Network criteria for genetic testing, were given pretest counseling and offered testing on the same day or referral for testing within 2 weeks.

Of the 3,811 women who completed the questionnaire, 24% (906) met NCCN criteria, 90% of whom were offered testing. However, only 52% (165) of patients who agreed to testing underwent genetic evaluation. This included 70% of patients who were offered same-day testing and 35% of patients who were offered a referral appointment for testing.

Conversations about HBOC and genetic testing can be complicated and may not be a patient’s initial priority. The authors should be commended for identifying the vast majority of high-risk patients. However, only half of patients meeting criteria completed testing and 10% who should have been offered testing were not – numbers still well below target.

Incorporation of family history questionnaires should become commonplace in the generalist’s office and optimizing EHRs may be an opportunity for rapid risk interpretation. As the success of same-day genetic testing was striking, opportunities for partnerships with insurance companies and private laboratories are likely needed to make this a more feasible option. Lastly, assessing women’s knowledge and attitudes around genetic testing could help to more specifically address barriers to testing in future interventions.

Improving genetic screening and testing completion rates requires a coordinated effort. Using tools and applications to optimize convenience (same-day testing, telemedicine) and simplification (electronic screening platforms), we can strive to appropriately detect all women at high risk for hereditary breast and ovarian cancers.

Michelle Lightfoot is a gynecologic oncology fellow at the Ohio State University in Columbus. She has no relevant financial disclosures. Email her at [email protected].

Researchers from general obstetrics and gynecology (ob.gyn.) practices in New York and Connecticut have shown that a 4-week intervention may improve genetic screening and testing rates for hereditary breast and ovarian cancers (HBOC).

Genetic screening and testing can reduce the morbidity and mortality from breast, ovarian, and endometrial cancers through prevention and early detection. Mark S. DeFrancesco, MD, of Westwood Women’s Health, Waterbury, Conn., and his colleagues reported that, in spite of the American College of Obstetricians and Gynecologists’ recommendation for ob.gyns. to regularly screen, counsel, and refer accordingly for HBOC (Obstet Gynecol. 2015;125:153843), the “incorporation of hereditary cancer risk assessment and testing remains underutilized in the [ob.gyn.] setting.” The authors have addressed this issue in their own practice with promising results and important caveats (Obstet Gynecol 2018;132:1121-9).

The intervention included a process evaluation, improvements to patient work flow, and training of providers by genetic counselors and engineering personnel from the testing laboratory (Myriad Genetics), which provided support for the study. Patients in the study completed a family history questionnaire and, those meeting National Comprehensive Cancer Center Network criteria for genetic testing, were given pretest counseling and offered testing on the same day or referral for testing within 2 weeks.

Of the 3,811 women who completed the questionnaire, 24% (906) met NCCN criteria, 90% of whom were offered testing. However, only 52% (165) of patients who agreed to testing underwent genetic evaluation. This included 70% of patients who were offered same-day testing and 35% of patients who were offered a referral appointment for testing.

Conversations about HBOC and genetic testing can be complicated and may not be a patient’s initial priority. The authors should be commended for identifying the vast majority of high-risk patients. However, only half of patients meeting criteria completed testing and 10% who should have been offered testing were not – numbers still well below target.

Incorporation of family history questionnaires should become commonplace in the generalist’s office and optimizing EHRs may be an opportunity for rapid risk interpretation. As the success of same-day genetic testing was striking, opportunities for partnerships with insurance companies and private laboratories are likely needed to make this a more feasible option. Lastly, assessing women’s knowledge and attitudes around genetic testing could help to more specifically address barriers to testing in future interventions.

Improving genetic screening and testing completion rates requires a coordinated effort. Using tools and applications to optimize convenience (same-day testing, telemedicine) and simplification (electronic screening platforms), we can strive to appropriately detect all women at high risk for hereditary breast and ovarian cancers.

Michelle Lightfoot is a gynecologic oncology fellow at the Ohio State University in Columbus. She has no relevant financial disclosures. Email her at [email protected].

MUNICH – Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate, according to recent trials and conference proceedings.

Male breast cancer is a rare, little-studied disease that was highlighted at the annual meeting of the European Society for Medical Oncology.

“This is a truly magnificent effort made by these authors,” said invited discussant Carolien Schroeder, MD, PhD, of the University Medical Center Groningen in the Netherlands, noting the challenges inherent to studies of niche cancer populations.

Previous studies have shown that men with MBC are usually hormone receptor positive (HR+) and older than women with MBC. Male patients also tend to present with more severe disease.

“[Male breast cancer patients] usually present with higher stages of disease; larger tumors, more nodal involvement, and more metastatic disease,” Dr. Schroeder said. “And 4%-16% may have genetic predisposition, usually due to a BRCA2 mutation.”

One retrospective study used data from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform to further knowledge of male patient characteristics, treatment types, and disease outcomes. ESME is a national database that stores patient information from 18 cancer centers in France.

“We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment,” said principal investigator Jean-Sébastien Frénel, MD, of the Institut de Cancérologie de l’Ouest in Nantes, France, in an interview.

The ESME study evaluated 16,701 patients with MBC: 16,552 women (99.11%) and 149 men (0.89%). Patients received at least one treatment between January 2008 and December 2014.

On average, male patients were older than females (mean: 68.1 years vs. 60.6 years), which lines up with existing data; in contrast, 78.4% of men were HR+, which is slightly lower than the widely described figure of 90%. Almost half of the HR+/human epidermal growth factor 2– (HER2–) male patients were given a frontline hormonal therapy (43%); of those, 44% received tamoxifen, 40% received an aromatase inhibitor (with or without a gonadotropin-releasing hormone analog [GnRH]), and 16% received other therapies. Outcomes were relatively similar between men and women: median progression-free survival (PFS) was 9.8 months for men, compared with 13.0 months for women. About one-quarter of HR+/HER2– men (27.6%) received frontline chemotherapy, resulting in a PFS of 6.9 months compared with 6.3 months for matched women. Overall survival was also slightly longer for men than matched women (41.8 months vs 34.9 months). In general, these statistics show that men and women received similar treatments and had similar outcomes.

“Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors,” Dr. Frénel said. “But few patients received aromatase inhibitors plus [GnRH] analogs despite some guidelines recommending that they should be given in combination.”

GnRH for men remains a topic of debate. Although aromatase inhibitors should be given with GnRH to avoid a negative feedback loop, gonadal suppression causes erectile dysfunction, thereby decreasing well-being. This dilemma is made worse by a lack of data on hormonal therapy for men with breast cancer.

To address this shortcoming, a prospective, randomized trial compared three different hormonal regimens for men. Male-GBG54 involved 55 men with breast cancer. For 6 months, patients received 1 of 3 treatment regimens: tamoxifen (20 mg/day), tamoxifen + GnRH (subcutaneous every 3 months), or exemestane (25 mg daily) + GnRH. Median estradiol levels were measured at 3 months and 6 months, and wellbeing was measured using questionnaires.

As expected, the results showed increased estradiol levels in the tamoxifen group and decreased levels in the GnRH group. Men were generally dissatisfied with GnRH therapy because of the erectile dysfunction it caused.

“Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients’ well-being and erectile function profoundly,” lead author Mattea Reinisch, MD, of Klinikum Essen-Mitte (Germany), said in an interview.

Dr. Schroeder agreed that tamoxifen should remain the standard treatment but suggested that the benefits of gonadal suppression may outweigh the downsides. “We need efficacy data for gonadal suppression,” she said. “After all, we are advising our premenopausal breast cancer patients to undergo the gonadal suppression therapy on a daily basis because of the oncological superiority, despite the toxicity they are also experiencing.”

Dr. Schroeder again called for efficacy data and described shortcomings of Male-GBG54: “[Dr. Reinisch and her colleagues] have chosen a biological surrogate endpoint, but what we’d really like, of course, [are] the efficacy data. The quality of life data are not breast-cancer specific, and these are only data for 6 months, whereas, particularly in the metastatic setting, the compliance issue after 6 months is also relevant.”

Reflecting on the data from ESME and Male-GBG54, Dr. Schroeder said, “I think this field is maturing, and intervention trials have proven themselves to be possible in this niche population.”

Looking to the future, Dr. Schroeder suggested that male breast cancer can be studied either in separate trials from women (focusing on sex-specific targets), or in shared studies, as many disease characteristics are the same regardless of sex. She also said that worse disease in men is likely due to delayed presentation rather than biological differences between men and women.

“This leaves room for improvement,” Dr. Schroeder said. “We still need to work on the awareness of this disease.”

Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
 

SOURCES: Sirieix J et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.

MUNICH – Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate, according to recent trials and conference proceedings.

Male breast cancer is a rare, little-studied disease that was highlighted at the annual meeting of the European Society for Medical Oncology.

“This is a truly magnificent effort made by these authors,” said invited discussant Carolien Schroeder, MD, PhD, of the University Medical Center Groningen in the Netherlands, noting the challenges inherent to studies of niche cancer populations.

Previous studies have shown that men with MBC are usually hormone receptor positive (HR+) and older than women with MBC. Male patients also tend to present with more severe disease.

“[Male breast cancer patients] usually present with higher stages of disease; larger tumors, more nodal involvement, and more metastatic disease,” Dr. Schroeder said. “And 4%-16% may have genetic predisposition, usually due to a BRCA2 mutation.”

One retrospective study used data from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform to further knowledge of male patient characteristics, treatment types, and disease outcomes. ESME is a national database that stores patient information from 18 cancer centers in France.

“We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment,” said principal investigator Jean-Sébastien Frénel, MD, of the Institut de Cancérologie de l’Ouest in Nantes, France, in an interview.

The ESME study evaluated 16,701 patients with MBC: 16,552 women (99.11%) and 149 men (0.89%). Patients received at least one treatment between January 2008 and December 2014.

On average, male patients were older than females (mean: 68.1 years vs. 60.6 years), which lines up with existing data; in contrast, 78.4% of men were HR+, which is slightly lower than the widely described figure of 90%. Almost half of the HR+/human epidermal growth factor 2– (HER2–) male patients were given a frontline hormonal therapy (43%); of those, 44% received tamoxifen, 40% received an aromatase inhibitor (with or without a gonadotropin-releasing hormone analog [GnRH]), and 16% received other therapies. Outcomes were relatively similar between men and women: median progression-free survival (PFS) was 9.8 months for men, compared with 13.0 months for women. About one-quarter of HR+/HER2– men (27.6%) received frontline chemotherapy, resulting in a PFS of 6.9 months compared with 6.3 months for matched women. Overall survival was also slightly longer for men than matched women (41.8 months vs 34.9 months). In general, these statistics show that men and women received similar treatments and had similar outcomes.

“Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors,” Dr. Frénel said. “But few patients received aromatase inhibitors plus [GnRH] analogs despite some guidelines recommending that they should be given in combination.”

GnRH for men remains a topic of debate. Although aromatase inhibitors should be given with GnRH to avoid a negative feedback loop, gonadal suppression causes erectile dysfunction, thereby decreasing well-being. This dilemma is made worse by a lack of data on hormonal therapy for men with breast cancer.

To address this shortcoming, a prospective, randomized trial compared three different hormonal regimens for men. Male-GBG54 involved 55 men with breast cancer. For 6 months, patients received 1 of 3 treatment regimens: tamoxifen (20 mg/day), tamoxifen + GnRH (subcutaneous every 3 months), or exemestane (25 mg daily) + GnRH. Median estradiol levels were measured at 3 months and 6 months, and wellbeing was measured using questionnaires.

As expected, the results showed increased estradiol levels in the tamoxifen group and decreased levels in the GnRH group. Men were generally dissatisfied with GnRH therapy because of the erectile dysfunction it caused.

“Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients’ well-being and erectile function profoundly,” lead author Mattea Reinisch, MD, of Klinikum Essen-Mitte (Germany), said in an interview.

Dr. Schroeder agreed that tamoxifen should remain the standard treatment but suggested that the benefits of gonadal suppression may outweigh the downsides. “We need efficacy data for gonadal suppression,” she said. “After all, we are advising our premenopausal breast cancer patients to undergo the gonadal suppression therapy on a daily basis because of the oncological superiority, despite the toxicity they are also experiencing.”

Dr. Schroeder again called for efficacy data and described shortcomings of Male-GBG54: “[Dr. Reinisch and her colleagues] have chosen a biological surrogate endpoint, but what we’d really like, of course, [are] the efficacy data. The quality of life data are not breast-cancer specific, and these are only data for 6 months, whereas, particularly in the metastatic setting, the compliance issue after 6 months is also relevant.”

Reflecting on the data from ESME and Male-GBG54, Dr. Schroeder said, “I think this field is maturing, and intervention trials have proven themselves to be possible in this niche population.”

Looking to the future, Dr. Schroeder suggested that male breast cancer can be studied either in separate trials from women (focusing on sex-specific targets), or in shared studies, as many disease characteristics are the same regardless of sex. She also said that worse disease in men is likely due to delayed presentation rather than biological differences between men and women.

“This leaves room for improvement,” Dr. Schroeder said. “We still need to work on the awareness of this disease.”

Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
 

SOURCES: Sirieix J et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.

MUNICH – Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate, according to recent trials and conference proceedings.

Male breast cancer is a rare, little-studied disease that was highlighted at the annual meeting of the European Society for Medical Oncology.

“This is a truly magnificent effort made by these authors,” said invited discussant Carolien Schroeder, MD, PhD, of the University Medical Center Groningen in the Netherlands, noting the challenges inherent to studies of niche cancer populations.

Previous studies have shown that men with MBC are usually hormone receptor positive (HR+) and older than women with MBC. Male patients also tend to present with more severe disease.

“[Male breast cancer patients] usually present with higher stages of disease; larger tumors, more nodal involvement, and more metastatic disease,” Dr. Schroeder said. “And 4%-16% may have genetic predisposition, usually due to a BRCA2 mutation.”

One retrospective study used data from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform to further knowledge of male patient characteristics, treatment types, and disease outcomes. ESME is a national database that stores patient information from 18 cancer centers in France.

“We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment,” said principal investigator Jean-Sébastien Frénel, MD, of the Institut de Cancérologie de l’Ouest in Nantes, France, in an interview.

The ESME study evaluated 16,701 patients with MBC: 16,552 women (99.11%) and 149 men (0.89%). Patients received at least one treatment between January 2008 and December 2014.

On average, male patients were older than females (mean: 68.1 years vs. 60.6 years), which lines up with existing data; in contrast, 78.4% of men were HR+, which is slightly lower than the widely described figure of 90%. Almost half of the HR+/human epidermal growth factor 2– (HER2–) male patients were given a frontline hormonal therapy (43%); of those, 44% received tamoxifen, 40% received an aromatase inhibitor (with or without a gonadotropin-releasing hormone analog [GnRH]), and 16% received other therapies. Outcomes were relatively similar between men and women: median progression-free survival (PFS) was 9.8 months for men, compared with 13.0 months for women. About one-quarter of HR+/HER2– men (27.6%) received frontline chemotherapy, resulting in a PFS of 6.9 months compared with 6.3 months for matched women. Overall survival was also slightly longer for men than matched women (41.8 months vs 34.9 months). In general, these statistics show that men and women received similar treatments and had similar outcomes.

“Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors,” Dr. Frénel said. “But few patients received aromatase inhibitors plus [GnRH] analogs despite some guidelines recommending that they should be given in combination.”

GnRH for men remains a topic of debate. Although aromatase inhibitors should be given with GnRH to avoid a negative feedback loop, gonadal suppression causes erectile dysfunction, thereby decreasing well-being. This dilemma is made worse by a lack of data on hormonal therapy for men with breast cancer.

To address this shortcoming, a prospective, randomized trial compared three different hormonal regimens for men. Male-GBG54 involved 55 men with breast cancer. For 6 months, patients received 1 of 3 treatment regimens: tamoxifen (20 mg/day), tamoxifen + GnRH (subcutaneous every 3 months), or exemestane (25 mg daily) + GnRH. Median estradiol levels were measured at 3 months and 6 months, and wellbeing was measured using questionnaires.

As expected, the results showed increased estradiol levels in the tamoxifen group and decreased levels in the GnRH group. Men were generally dissatisfied with GnRH therapy because of the erectile dysfunction it caused.

“Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients’ well-being and erectile function profoundly,” lead author Mattea Reinisch, MD, of Klinikum Essen-Mitte (Germany), said in an interview.

Dr. Schroeder agreed that tamoxifen should remain the standard treatment but suggested that the benefits of gonadal suppression may outweigh the downsides. “We need efficacy data for gonadal suppression,” she said. “After all, we are advising our premenopausal breast cancer patients to undergo the gonadal suppression therapy on a daily basis because of the oncological superiority, despite the toxicity they are also experiencing.”

Dr. Schroeder again called for efficacy data and described shortcomings of Male-GBG54: “[Dr. Reinisch and her colleagues] have chosen a biological surrogate endpoint, but what we’d really like, of course, [are] the efficacy data. The quality of life data are not breast-cancer specific, and these are only data for 6 months, whereas, particularly in the metastatic setting, the compliance issue after 6 months is also relevant.”

Reflecting on the data from ESME and Male-GBG54, Dr. Schroeder said, “I think this field is maturing, and intervention trials have proven themselves to be possible in this niche population.”

Looking to the future, Dr. Schroeder suggested that male breast cancer can be studied either in separate trials from women (focusing on sex-specific targets), or in shared studies, as many disease characteristics are the same regardless of sex. She also said that worse disease in men is likely due to delayed presentation rather than biological differences between men and women.

“This leaves room for improvement,” Dr. Schroeder said. “We still need to work on the awareness of this disease.”

Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
 

SOURCES: Sirieix J et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.

MUNICH – A combination of the selective phosphoinositide 3-kinase inhibitor alpelisib and fulvestrant (Faslodex) was associated with significantly better progression-free survival than placebo plus fulvestrant in patients with hormone receptor–positive, HER2-negative breast cancer with PIK3CA mutations, investigators in the SOLAR-1 trial reported.

Neil Osterweil/MDedge News

The addition of alpelisib, an inhibitor of the alpha isoform of the phosphoinositide 3-kinase (PI3K), to fulvestrant, a selective estrogen receptor modifier, was associated with a 35% improvement in progression-free survival (PFS), reported Fabrice André, MD, of Institut Gustave Roussy, Villejuif, France.

“Alpelisib plus fulvestrant is a potential new treatment option for patients with PIK3CA-mutant, hormone receptor–positive, HER2-negative advanced breast cancer who have progressed on prior endocrine therapy, with or without a CDK 4/6 [cyclin-dependent kinases 4/6] inhibitor,” he said in a podium presentation at the European Society for Medical Oncology Congress.

Unlike other PI3K inhibitors which have activity spanning the alpha, beta, gamma, and delta isoforms of PI3K, alpelisib is specific for only the alpha isoform, giving it a safety profile that compares favorably with other agents in its class, Dr. André said.

Results of other studies combining PI3K inhibition with endocrine therapy have not borne especially sweet fruit. For example, the SANDPIPER trial, a study of the combination of fulvestrant and the PI3K inhibitor idelalisib (Zydelig) presented at the 2018 annual meeting of the American Society of Clinical Oncology, showed a benefit of 2 months more PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half of all patients treated with the combination.

In the SOLAR-1 trial, investigators randomized 572 postmenopausal women, or men (sex of patients not shown), with hormone receptor–positive, HER2-negative advanced breast cancer. Of the 572 patients, 341 were determined to have PIK3CA mutations.

To be eligible for the study, patients had to have good Eastern Cooperative Oncology Group performance status (1 or less) and have received one or more prior lines of endocrine therapy but no chemotherapy for advanced breast cancer.

Patients who had previously received fulvestrant, any PI3K inhibitor, Akt inhibitor, or mammalian target of rapamycin inhibitor were excluded.

The patients were randomly assigned to receive intramuscular fulvestrant 500 mg on days 1 and 15 of treatment cycle 1 and then every 28 days, plus either oral alpelisib (300 mg daily) or placebo.

Locally assessed PFS in patients with PIK3CA mutations, the primary endpoint, favored alpelisib. At a median follow-up of 20 months, the median PFS with alpelisib was 11 months, versus 5.7 months for placebo. The hazard ratio for progression with alpelisib was 0.65 (P = .00065).

A blinded independent review committee assessment of 50% of patients in the PIK3CA-mutant cohort supported the investigator-assessed findings, with a median PFS of 11.1 months with alpelisib, versus 3.7 months with placebo.

In contrast, a proof-of-concept analysis of the 231 patients without PIK3CA mutations could not show a benefit for alpelisib over placebo.

In the PIK3CA-mutant cohort, the overall response rates among patients with measurable disease were 35.7% with alpelisib versus 16.2% with placebo (P = .0002). Respective response rates among all patients were 26.6% and 12.8% (P = .0006).

Adverse events in the entire trial population included hyperglycemia leading to discontinuation of alpelisib in 6.3% of patients and rash leading to discontinuation of the drug in 3.2% of patients. There were no discontinuations for either hyperglycemia or rash in the placebo arm.

The hyperglycemia can be managed with metformin, Dr. André said.

At a briefing prior to presentation of the SOLAR-1 data in a symposium, briefing discussant Nadia Harbeck, MD, of the University of Munich Medical Center said that the trial represents a significant advance.

“We have numerous talks, also phase 3 trials, with PI3-kinase inhibitors where we saw marginal benefit, and the drugs weren’t usable in clinical practice because the tolerability was so bad. So this is now the first phase 3 data proving that if you have a targeted drug and the tumor has the target, you can actually almost double progression-free survival, and I think this will change the way we practice,” she said.

Neil Osterweil/MDedge News

Rebecca Dent, MD, a senior consultant at the National Cancer Centre Singapore, the invited discussant at the symposium, complimented the SOLAR-1 investigators for conducting a “clinically homogeneous, biomarker-driven clinical trial reflecting new pathways to registration.”

She suggested that the significant clinical toxicities seen with PI3K inhibitors might be ameliorated with different dosing schedules, pharmacodynamic endpoints such as hyperglycemia, or potential prophylaxis.

The trial demonstrated a clinically meaningful absolute PFS benefit, the best in class, but updated data, including overall survival data, are still needed, Dr. Dent said. “We also need to see the quality-of-life data; this is what’s important for our patients. Is this improving progression-free survival, is it improving quality of life, and is it improving overall survival? Only the future will tell.”

SOLAR-1 was sponsored by Novartis. Dr. André disclosed research grants from Novartis and others. Dr. Dent disclosed advisory board, honoraria, or travel support from Novartis and others. Dr. Harbeck disclosed honoraria for consulting and lecturing for Pfizer and others.

SOURCE: Andre F et al. ESMO 2018, Abstract LBA3_PR.

MUNICH – A combination of the selective phosphoinositide 3-kinase inhibitor alpelisib and fulvestrant (Faslodex) was associated with significantly better progression-free survival than placebo plus fulvestrant in patients with hormone receptor–positive, HER2-negative breast cancer with PIK3CA mutations, investigators in the SOLAR-1 trial reported.

Neil Osterweil/MDedge News

The addition of alpelisib, an inhibitor of the alpha isoform of the phosphoinositide 3-kinase (PI3K), to fulvestrant, a selective estrogen receptor modifier, was associated with a 35% improvement in progression-free survival (PFS), reported Fabrice André, MD, of Institut Gustave Roussy, Villejuif, France.

“Alpelisib plus fulvestrant is a potential new treatment option for patients with PIK3CA-mutant, hormone receptor–positive, HER2-negative advanced breast cancer who have progressed on prior endocrine therapy, with or without a CDK 4/6 [cyclin-dependent kinases 4/6] inhibitor,” he said in a podium presentation at the European Society for Medical Oncology Congress.

Unlike other PI3K inhibitors which have activity spanning the alpha, beta, gamma, and delta isoforms of PI3K, alpelisib is specific for only the alpha isoform, giving it a safety profile that compares favorably with other agents in its class, Dr. André said.

Results of other studies combining PI3K inhibition with endocrine therapy have not borne especially sweet fruit. For example, the SANDPIPER trial, a study of the combination of fulvestrant and the PI3K inhibitor idelalisib (Zydelig) presented at the 2018 annual meeting of the American Society of Clinical Oncology, showed a benefit of 2 months more PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half of all patients treated with the combination.

In the SOLAR-1 trial, investigators randomized 572 postmenopausal women, or men (sex of patients not shown), with hormone receptor–positive, HER2-negative advanced breast cancer. Of the 572 patients, 341 were determined to have PIK3CA mutations.

To be eligible for the study, patients had to have good Eastern Cooperative Oncology Group performance status (1 or less) and have received one or more prior lines of endocrine therapy but no chemotherapy for advanced breast cancer.

Patients who had previously received fulvestrant, any PI3K inhibitor, Akt inhibitor, or mammalian target of rapamycin inhibitor were excluded.

The patients were randomly assigned to receive intramuscular fulvestrant 500 mg on days 1 and 15 of treatment cycle 1 and then every 28 days, plus either oral alpelisib (300 mg daily) or placebo.

Locally assessed PFS in patients with PIK3CA mutations, the primary endpoint, favored alpelisib. At a median follow-up of 20 months, the median PFS with alpelisib was 11 months, versus 5.7 months for placebo. The hazard ratio for progression with alpelisib was 0.65 (P = .00065).

A blinded independent review committee assessment of 50% of patients in the PIK3CA-mutant cohort supported the investigator-assessed findings, with a median PFS of 11.1 months with alpelisib, versus 3.7 months with placebo.

In contrast, a proof-of-concept analysis of the 231 patients without PIK3CA mutations could not show a benefit for alpelisib over placebo.

In the PIK3CA-mutant cohort, the overall response rates among patients with measurable disease were 35.7% with alpelisib versus 16.2% with placebo (P = .0002). Respective response rates among all patients were 26.6% and 12.8% (P = .0006).

Adverse events in the entire trial population included hyperglycemia leading to discontinuation of alpelisib in 6.3% of patients and rash leading to discontinuation of the drug in 3.2% of patients. There were no discontinuations for either hyperglycemia or rash in the placebo arm.

The hyperglycemia can be managed with metformin, Dr. André said.

At a briefing prior to presentation of the SOLAR-1 data in a symposium, briefing discussant Nadia Harbeck, MD, of the University of Munich Medical Center said that the trial represents a significant advance.

“We have numerous talks, also phase 3 trials, with PI3-kinase inhibitors where we saw marginal benefit, and the drugs weren’t usable in clinical practice because the tolerability was so bad. So this is now the first phase 3 data proving that if you have a targeted drug and the tumor has the target, you can actually almost double progression-free survival, and I think this will change the way we practice,” she said.

Neil Osterweil/MDedge News

Rebecca Dent, MD, a senior consultant at the National Cancer Centre Singapore, the invited discussant at the symposium, complimented the SOLAR-1 investigators for conducting a “clinically homogeneous, biomarker-driven clinical trial reflecting new pathways to registration.”

She suggested that the significant clinical toxicities seen with PI3K inhibitors might be ameliorated with different dosing schedules, pharmacodynamic endpoints such as hyperglycemia, or potential prophylaxis.

The trial demonstrated a clinically meaningful absolute PFS benefit, the best in class, but updated data, including overall survival data, are still needed, Dr. Dent said. “We also need to see the quality-of-life data; this is what’s important for our patients. Is this improving progression-free survival, is it improving quality of life, and is it improving overall survival? Only the future will tell.”

SOLAR-1 was sponsored by Novartis. Dr. André disclosed research grants from Novartis and others. Dr. Dent disclosed advisory board, honoraria, or travel support from Novartis and others. Dr. Harbeck disclosed honoraria for consulting and lecturing for Pfizer and others.

SOURCE: Andre F et al. ESMO 2018, Abstract LBA3_PR.

MUNICH – A combination of the selective phosphoinositide 3-kinase inhibitor alpelisib and fulvestrant (Faslodex) was associated with significantly better progression-free survival than placebo plus fulvestrant in patients with hormone receptor–positive, HER2-negative breast cancer with PIK3CA mutations, investigators in the SOLAR-1 trial reported.

Neil Osterweil/MDedge News

The addition of alpelisib, an inhibitor of the alpha isoform of the phosphoinositide 3-kinase (PI3K), to fulvestrant, a selective estrogen receptor modifier, was associated with a 35% improvement in progression-free survival (PFS), reported Fabrice André, MD, of Institut Gustave Roussy, Villejuif, France.

“Alpelisib plus fulvestrant is a potential new treatment option for patients with PIK3CA-mutant, hormone receptor–positive, HER2-negative advanced breast cancer who have progressed on prior endocrine therapy, with or without a CDK 4/6 [cyclin-dependent kinases 4/6] inhibitor,” he said in a podium presentation at the European Society for Medical Oncology Congress.

Unlike other PI3K inhibitors which have activity spanning the alpha, beta, gamma, and delta isoforms of PI3K, alpelisib is specific for only the alpha isoform, giving it a safety profile that compares favorably with other agents in its class, Dr. André said.

Results of other studies combining PI3K inhibition with endocrine therapy have not borne especially sweet fruit. For example, the SANDPIPER trial, a study of the combination of fulvestrant and the PI3K inhibitor idelalisib (Zydelig) presented at the 2018 annual meeting of the American Society of Clinical Oncology, showed a benefit of 2 months more PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half of all patients treated with the combination.

In the SOLAR-1 trial, investigators randomized 572 postmenopausal women, or men (sex of patients not shown), with hormone receptor–positive, HER2-negative advanced breast cancer. Of the 572 patients, 341 were determined to have PIK3CA mutations.

To be eligible for the study, patients had to have good Eastern Cooperative Oncology Group performance status (1 or less) and have received one or more prior lines of endocrine therapy but no chemotherapy for advanced breast cancer.

Patients who had previously received fulvestrant, any PI3K inhibitor, Akt inhibitor, or mammalian target of rapamycin inhibitor were excluded.

The patients were randomly assigned to receive intramuscular fulvestrant 500 mg on days 1 and 15 of treatment cycle 1 and then every 28 days, plus either oral alpelisib (300 mg daily) or placebo.

Locally assessed PFS in patients with PIK3CA mutations, the primary endpoint, favored alpelisib. At a median follow-up of 20 months, the median PFS with alpelisib was 11 months, versus 5.7 months for placebo. The hazard ratio for progression with alpelisib was 0.65 (P = .00065).

A blinded independent review committee assessment of 50% of patients in the PIK3CA-mutant cohort supported the investigator-assessed findings, with a median PFS of 11.1 months with alpelisib, versus 3.7 months with placebo.

In contrast, a proof-of-concept analysis of the 231 patients without PIK3CA mutations could not show a benefit for alpelisib over placebo.

In the PIK3CA-mutant cohort, the overall response rates among patients with measurable disease were 35.7% with alpelisib versus 16.2% with placebo (P = .0002). Respective response rates among all patients were 26.6% and 12.8% (P = .0006).

Adverse events in the entire trial population included hyperglycemia leading to discontinuation of alpelisib in 6.3% of patients and rash leading to discontinuation of the drug in 3.2% of patients. There were no discontinuations for either hyperglycemia or rash in the placebo arm.

The hyperglycemia can be managed with metformin, Dr. André said.

At a briefing prior to presentation of the SOLAR-1 data in a symposium, briefing discussant Nadia Harbeck, MD, of the University of Munich Medical Center said that the trial represents a significant advance.

“We have numerous talks, also phase 3 trials, with PI3-kinase inhibitors where we saw marginal benefit, and the drugs weren’t usable in clinical practice because the tolerability was so bad. So this is now the first phase 3 data proving that if you have a targeted drug and the tumor has the target, you can actually almost double progression-free survival, and I think this will change the way we practice,” she said.

Neil Osterweil/MDedge News

Rebecca Dent, MD, a senior consultant at the National Cancer Centre Singapore, the invited discussant at the symposium, complimented the SOLAR-1 investigators for conducting a “clinically homogeneous, biomarker-driven clinical trial reflecting new pathways to registration.”

She suggested that the significant clinical toxicities seen with PI3K inhibitors might be ameliorated with different dosing schedules, pharmacodynamic endpoints such as hyperglycemia, or potential prophylaxis.

The trial demonstrated a clinically meaningful absolute PFS benefit, the best in class, but updated data, including overall survival data, are still needed, Dr. Dent said. “We also need to see the quality-of-life data; this is what’s important for our patients. Is this improving progression-free survival, is it improving quality of life, and is it improving overall survival? Only the future will tell.”

SOLAR-1 was sponsored by Novartis. Dr. André disclosed research grants from Novartis and others. Dr. Dent disclosed advisory board, honoraria, or travel support from Novartis and others. Dr. Harbeck disclosed honoraria for consulting and lecturing for Pfizer and others.

SOURCE: Andre F et al. ESMO 2018, Abstract LBA3_PR.