Focused ultrasound for ablation of the subthalamic nucleus in one hemisphere improved motor features in a selected group of patients with markedly asymmetric Parkinson’s disease, but was associated with a high rate of adverse events, including dyskinesias and other neurologic complications, in a new randomized, sham-controlled trial.

“Longer-term and larger trials are needed to determine the role of focused ultrasound subthalamotomy in the management of Parkinson’s disease and its effect as compared with other available treatments, including deep-brain stimulation,” the authors concluded.

The trial was published online Dec.24, 2020, in the New England Journal of Medicine.

An accompanying editorial concluded that the high rate of adverse events and the lack of ability to modulate treatment over time to treat prominent tremor “raise questions about the appropriate implementation of focused ultrasound–produced lesions for the treatment of Parkinson’s disease.”
 

A scalpel-free alternative to brain surgery

The study authors, led by Raul Martinez-Fernandez, MD, PhD, University Hospital HM Puerta del Sur, Mostoles, Spain, explained that, in severe cases of refractory motor manifestations such as tremor and motor complications, a neurosurgical approach using deep-brain stimulation of the subthalamic nucleus can be used. But to avoid craniotomy and electrode penetration, MRI-guided focused ultrasound for the ablation of deep-brain structures, including the subthalamic nucleus, is being investigated as a treatment for Parkinson’s disease.

Patients are potential candidates for ultrasound ablation if they have prominently asymmetric parkinsonism, if they are not considered to be clinically suitable candidates for surgery because of contraindications, or if they are reluctant to undergo a brain operation or to have an implanted device.

The current trial involved 40 patients with markedly asymmetric Parkinson’s disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery. They were randomly assigned in a 2:1 ratio to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure.

Results showed that the mean Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) motor score for the more affected side – which was the primary endpoint – decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points); and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points). The between-group difference was 8.1 points (P < .001).

The change from baseline in the MDS-UPDRS III score for the more affected side in patients who underwent active treatment varied, ranging from 5% to 95%; the changes were qualitatively more evident for reduction of tremor and rigidity than for bradykinesia.

Adverse events in the active-treatment group were the following:

• Dyskinesia in the off-medication state in six patients and in the on-medication state in six, which persisted in three and one, respectively, at 4 months.
• Weakness on the treated side in five patients, which persisted in two at 4 months.
• Speech disturbance in 15 patients, which persisted in 3 at 4 months.
• Facial weakness in three patients, which persisted in one at 4 months.
• in 13 patients, which persisted in two at 4 months.

In six patients in the active-treatment group, some of these deficits were present at 12 months.

The researchers noted that an approach that has been suggested to reduce the risk of dyskinesias has been to extend ablations dorsal to the subthalamic nucleus in order to interrupt the pallidothalamic-projecting neurons.

The study also showed a greater reduction in the use of dopaminergic medication in the active-treatment group versus the control group, but the researchers noted that the 95% confidence intervals for this and other secondary outcomes were not adjusted for multiple comparisons, so no definite conclusions can be drawn from these data.

They also pointed out that subthalamotomy was performed in one hemisphere, and the natural evolution of Parkinson’s disease eventually leads to motor impairment on both sides of the body in most patients.

“The likely need for an increase in the daily dose of levodopa equivalent to maintain function on the untreated side of the body could lead to the development of dyskinesias on the treated side. However, the few open-label studies of long-term (≥36 months) follow-up of radiofrequency subthalamotomy performed in one hemisphere do not provide support for this concern,” they said.
 

An important step, but improvements are needed

In an accompanying editorial, Joel S. Perlmutter, MD, and Mwiza Ushe, MD, Washington University, St. Louis, noted that surgical deep brain stimulation of the left and right subthalamic nuclei has shown a reduction in the severity of motor signs of 40%-60% and a reduction in medication use of up to 50%. But this technique involves a small craniotomy with implantation of stimulating electrodes, which has a 1%-5% risk of major adverse events such as hemorrhage, stroke, or infection.

Less severe complications include dystonia, dysarthria, gait impairment, dyskinesia, swallowing dysfunction, or change in verbal fluency; however, modification of the device programming may alleviate these effects. Nevertheless, some patients are wary of the implantation surgery and hardware and therefore decline to undergo deep-brain stimulation, the editorialists explained.

“The development of alternative procedures to deep-brain stimulation is important to the field of Parkinson’s disease treatment. The current trial begins the path to that goal, and improvements in targeting may improve the risk-benefit ratio and permit the use of lesions in both hemispheres, which would widen the population of eligible patients,” Dr. Perlmutter and Dr. Ushe wrote.

They pointed out that limiting the treatment to one side of the brain by ultrasound-produced lesioning constrains the application, since most patients with Parkinson’s disease have progression of symptoms on both sides of the body.

“The potential advantages and limitations of focused ultrasound–produced lesioning should be discussed with patients. We hope that improved technique will reduce the associated risks and increase the applicability of this provocative procedure,” the editorialists concluded.

This study was supported by Insightec, the Focused Ultrasound Foundation, Fundacion MAPFRE, Fundacion Hospitales de Madrid, and the University of Virginia Center of Excellence. Dr. Martinez-Fernandez reported receiving for consultancy fees for Insightec. Dr. Ushe reported non-financial support for Abbott outside the submitted work. Dr. Perlmutter disclosed no relevant financial relationships.

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

Focused ultrasound for ablation of the subthalamic nucleus in one hemisphere improved motor features in a selected group of patients with markedly asymmetric Parkinson’s disease, but was associated with a high rate of adverse events, including dyskinesias and other neurologic complications, in a new randomized, sham-controlled trial.

“Longer-term and larger trials are needed to determine the role of focused ultrasound subthalamotomy in the management of Parkinson’s disease and its effect as compared with other available treatments, including deep-brain stimulation,” the authors concluded.

The trial was published online Dec.24, 2020, in the New England Journal of Medicine.

An accompanying editorial concluded that the high rate of adverse events and the lack of ability to modulate treatment over time to treat prominent tremor “raise questions about the appropriate implementation of focused ultrasound–produced lesions for the treatment of Parkinson’s disease.”
 

A scalpel-free alternative to brain surgery

The study authors, led by Raul Martinez-Fernandez, MD, PhD, University Hospital HM Puerta del Sur, Mostoles, Spain, explained that, in severe cases of refractory motor manifestations such as tremor and motor complications, a neurosurgical approach using deep-brain stimulation of the subthalamic nucleus can be used. But to avoid craniotomy and electrode penetration, MRI-guided focused ultrasound for the ablation of deep-brain structures, including the subthalamic nucleus, is being investigated as a treatment for Parkinson’s disease.

Patients are potential candidates for ultrasound ablation if they have prominently asymmetric parkinsonism, if they are not considered to be clinically suitable candidates for surgery because of contraindications, or if they are reluctant to undergo a brain operation or to have an implanted device.

The current trial involved 40 patients with markedly asymmetric Parkinson’s disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery. They were randomly assigned in a 2:1 ratio to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure.

Results showed that the mean Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) motor score for the more affected side – which was the primary endpoint – decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points); and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points). The between-group difference was 8.1 points (P < .001).

The change from baseline in the MDS-UPDRS III score for the more affected side in patients who underwent active treatment varied, ranging from 5% to 95%; the changes were qualitatively more evident for reduction of tremor and rigidity than for bradykinesia.

Adverse events in the active-treatment group were the following:

• Dyskinesia in the off-medication state in six patients and in the on-medication state in six, which persisted in three and one, respectively, at 4 months.
• Weakness on the treated side in five patients, which persisted in two at 4 months.
• Speech disturbance in 15 patients, which persisted in 3 at 4 months.
• Facial weakness in three patients, which persisted in one at 4 months.
• in 13 patients, which persisted in two at 4 months.

In six patients in the active-treatment group, some of these deficits were present at 12 months.

The researchers noted that an approach that has been suggested to reduce the risk of dyskinesias has been to extend ablations dorsal to the subthalamic nucleus in order to interrupt the pallidothalamic-projecting neurons.

The study also showed a greater reduction in the use of dopaminergic medication in the active-treatment group versus the control group, but the researchers noted that the 95% confidence intervals for this and other secondary outcomes were not adjusted for multiple comparisons, so no definite conclusions can be drawn from these data.

They also pointed out that subthalamotomy was performed in one hemisphere, and the natural evolution of Parkinson’s disease eventually leads to motor impairment on both sides of the body in most patients.

“The likely need for an increase in the daily dose of levodopa equivalent to maintain function on the untreated side of the body could lead to the development of dyskinesias on the treated side. However, the few open-label studies of long-term (≥36 months) follow-up of radiofrequency subthalamotomy performed in one hemisphere do not provide support for this concern,” they said.
 

An important step, but improvements are needed

In an accompanying editorial, Joel S. Perlmutter, MD, and Mwiza Ushe, MD, Washington University, St. Louis, noted that surgical deep brain stimulation of the left and right subthalamic nuclei has shown a reduction in the severity of motor signs of 40%-60% and a reduction in medication use of up to 50%. But this technique involves a small craniotomy with implantation of stimulating electrodes, which has a 1%-5% risk of major adverse events such as hemorrhage, stroke, or infection.

Less severe complications include dystonia, dysarthria, gait impairment, dyskinesia, swallowing dysfunction, or change in verbal fluency; however, modification of the device programming may alleviate these effects. Nevertheless, some patients are wary of the implantation surgery and hardware and therefore decline to undergo deep-brain stimulation, the editorialists explained.

“The development of alternative procedures to deep-brain stimulation is important to the field of Parkinson’s disease treatment. The current trial begins the path to that goal, and improvements in targeting may improve the risk-benefit ratio and permit the use of lesions in both hemispheres, which would widen the population of eligible patients,” Dr. Perlmutter and Dr. Ushe wrote.

They pointed out that limiting the treatment to one side of the brain by ultrasound-produced lesioning constrains the application, since most patients with Parkinson’s disease have progression of symptoms on both sides of the body.

“The potential advantages and limitations of focused ultrasound–produced lesioning should be discussed with patients. We hope that improved technique will reduce the associated risks and increase the applicability of this provocative procedure,” the editorialists concluded.

This study was supported by Insightec, the Focused Ultrasound Foundation, Fundacion MAPFRE, Fundacion Hospitales de Madrid, and the University of Virginia Center of Excellence. Dr. Martinez-Fernandez reported receiving for consultancy fees for Insightec. Dr. Ushe reported non-financial support for Abbott outside the submitted work. Dr. Perlmutter disclosed no relevant financial relationships.

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

Focused ultrasound for ablation of the subthalamic nucleus in one hemisphere improved motor features in a selected group of patients with markedly asymmetric Parkinson’s disease, but was associated with a high rate of adverse events, including dyskinesias and other neurologic complications, in a new randomized, sham-controlled trial.

“Longer-term and larger trials are needed to determine the role of focused ultrasound subthalamotomy in the management of Parkinson’s disease and its effect as compared with other available treatments, including deep-brain stimulation,” the authors concluded.

The trial was published online Dec.24, 2020, in the New England Journal of Medicine.

An accompanying editorial concluded that the high rate of adverse events and the lack of ability to modulate treatment over time to treat prominent tremor “raise questions about the appropriate implementation of focused ultrasound–produced lesions for the treatment of Parkinson’s disease.”
 

A scalpel-free alternative to brain surgery

The study authors, led by Raul Martinez-Fernandez, MD, PhD, University Hospital HM Puerta del Sur, Mostoles, Spain, explained that, in severe cases of refractory motor manifestations such as tremor and motor complications, a neurosurgical approach using deep-brain stimulation of the subthalamic nucleus can be used. But to avoid craniotomy and electrode penetration, MRI-guided focused ultrasound for the ablation of deep-brain structures, including the subthalamic nucleus, is being investigated as a treatment for Parkinson’s disease.

Patients are potential candidates for ultrasound ablation if they have prominently asymmetric parkinsonism, if they are not considered to be clinically suitable candidates for surgery because of contraindications, or if they are reluctant to undergo a brain operation or to have an implanted device.

The current trial involved 40 patients with markedly asymmetric Parkinson’s disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery. They were randomly assigned in a 2:1 ratio to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure.

Results showed that the mean Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) motor score for the more affected side – which was the primary endpoint – decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points); and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points). The between-group difference was 8.1 points (P < .001).

The change from baseline in the MDS-UPDRS III score for the more affected side in patients who underwent active treatment varied, ranging from 5% to 95%; the changes were qualitatively more evident for reduction of tremor and rigidity than for bradykinesia.

Adverse events in the active-treatment group were the following:

• Dyskinesia in the off-medication state in six patients and in the on-medication state in six, which persisted in three and one, respectively, at 4 months.
• Weakness on the treated side in five patients, which persisted in two at 4 months.
• Speech disturbance in 15 patients, which persisted in 3 at 4 months.
• Facial weakness in three patients, which persisted in one at 4 months.
• in 13 patients, which persisted in two at 4 months.

In six patients in the active-treatment group, some of these deficits were present at 12 months.

The researchers noted that an approach that has been suggested to reduce the risk of dyskinesias has been to extend ablations dorsal to the subthalamic nucleus in order to interrupt the pallidothalamic-projecting neurons.

The study also showed a greater reduction in the use of dopaminergic medication in the active-treatment group versus the control group, but the researchers noted that the 95% confidence intervals for this and other secondary outcomes were not adjusted for multiple comparisons, so no definite conclusions can be drawn from these data.

They also pointed out that subthalamotomy was performed in one hemisphere, and the natural evolution of Parkinson’s disease eventually leads to motor impairment on both sides of the body in most patients.

“The likely need for an increase in the daily dose of levodopa equivalent to maintain function on the untreated side of the body could lead to the development of dyskinesias on the treated side. However, the few open-label studies of long-term (≥36 months) follow-up of radiofrequency subthalamotomy performed in one hemisphere do not provide support for this concern,” they said.
 

An important step, but improvements are needed

In an accompanying editorial, Joel S. Perlmutter, MD, and Mwiza Ushe, MD, Washington University, St. Louis, noted that surgical deep brain stimulation of the left and right subthalamic nuclei has shown a reduction in the severity of motor signs of 40%-60% and a reduction in medication use of up to 50%. But this technique involves a small craniotomy with implantation of stimulating electrodes, which has a 1%-5% risk of major adverse events such as hemorrhage, stroke, or infection.

Less severe complications include dystonia, dysarthria, gait impairment, dyskinesia, swallowing dysfunction, or change in verbal fluency; however, modification of the device programming may alleviate these effects. Nevertheless, some patients are wary of the implantation surgery and hardware and therefore decline to undergo deep-brain stimulation, the editorialists explained.

“The development of alternative procedures to deep-brain stimulation is important to the field of Parkinson’s disease treatment. The current trial begins the path to that goal, and improvements in targeting may improve the risk-benefit ratio and permit the use of lesions in both hemispheres, which would widen the population of eligible patients,” Dr. Perlmutter and Dr. Ushe wrote.

They pointed out that limiting the treatment to one side of the brain by ultrasound-produced lesioning constrains the application, since most patients with Parkinson’s disease have progression of symptoms on both sides of the body.

“The potential advantages and limitations of focused ultrasound–produced lesioning should be discussed with patients. We hope that improved technique will reduce the associated risks and increase the applicability of this provocative procedure,” the editorialists concluded.

This study was supported by Insightec, the Focused Ultrasound Foundation, Fundacion MAPFRE, Fundacion Hospitales de Madrid, and the University of Virginia Center of Excellence. Dr. Martinez-Fernandez reported receiving for consultancy fees for Insightec. Dr. Ushe reported non-financial support for Abbott outside the submitted work. Dr. Perlmutter disclosed no relevant financial relationships.

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

Breast cancer patients treated with curative intent do not often experience symptoms related to the cancer itself, and treatment toxicities may impact adherence and subsequently prognosis. Mittendorf et al reported on patient reported outcomes (PROs) from the phase 3 IMpassion031 trial which showed pCR improvement with atezolizumab/chemotherapy compared to placebo/chemotherapy for neoadjuvant early-stage TNBC. Health-related quality of life items and treatment-related symptoms worsened similarly in both arms during neoadjuvant therapy, and recovered/stabilized in the adjuvant setting. Further exploration of immunotherapy PROs is warranted, as clinical benefit is seen with these agents and they do not appear to negatively impact functioning and patient experience with treatment long-term. Side effect profiles of immunotherapy and standard chemotherapy are different, and design of immunotherapy-specific PROs are desired.

The PRIME 2 10 year results evaluating the role of whole breast irradiation in women ≥65 years with early-stage HR-positive breast cancer receiving hormonal therapy showed RT reduced risk of local recurrence from 9.8% to 0.9% at 10 years (p=0.0008). Patients with low ER tumors had higher 10 year local recurrence rate compared to high ER tumors (18.8% versus 9.2% (p0.007)). Rates of overall survival (80.4% in no RT group vs 81.0% in RT group) and metastasis free survival were similar. A shared decision making approach is key, carefully weighing benefits and risks, considering pathologic features, patient preferences and co-morbidities that may influence endocrine therapy adherence. The impact of molecular subtypes and genomic assays is also being explored to help assess radiation benefit and guide treatment recommendations.

Breast cancer in young women presents unique challenges considering the lifetime period during which diagnosis occurs. Previous studies have supported the safety of pregnancy after breast cancer and guidelines recommend oncofertility counseling in young patients. Blondeaux et al found that breast cancer patients had a 60% lower chance of pregnancy after treatment and were more likely to have complications including low birth weight, small for gestational age, preterm delivery and cesarean section. Although increased risk of congenital abnormalities did not appear to be statistically significant, the HR was 1.63. Importantly, pregnancy after breast cancer did not negatively impact maternal outcomes. This study further supports the safety of pregnancy after breast cancer, highlights the need for close monitoring of pregnancies in these women, and emphasizes the importance of fertility and family planning discussion, which is most optimally provided in a multidisciplinary fashion.

References:

Dent R, Oliveira AM, Isakoff SJ, Im SA, Espié M, Blau S, Saura C, Wongchenko MJ, Xu N, Bradley D, Reilly SJ, Mani A, Kim SB. Final results of the double-blind placebo (PBO)-controlled randomised phase II LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for inoperable locally advanced/metastatic triple-negative breast cancer (mTNBC). Presented during 2020 ESMO breast cancer virtual meeting; May 23-24, 2020. Abstract 139O.

Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020;38:423-433.

Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396:1090-1100.

King-Kallimanis BL, Howie LJ, Roydhouse JK, Singh H, Theoret MR, Blumenthal GM, Kluetz PG. Patient reported outcomes in anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data submitted and future directions. Clin Trials. 2019;16:322-326.

Fodor A, Brombin C, Mangili P, Borroni F, Pasetti M, Tummineri R, Zerbetto F, Longobardi B, Perna L, Dell'Oca I, Deantoni CL, Deli AM, Chiara A, Broggi S, Castriconi R, Esposito PG, Slim N, Passoni P, Baroni S, Villa SL, Rancoita PMV, Fiorino C, Del Vecchio A, Bianchini G, Gentilini OD, Di Serio MS, Di Muzio NG. Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized? Breast. 2020;55:45-54.

Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, Peccatori FA. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47:74-83.

Breast cancer patients treated with curative intent do not often experience symptoms related to the cancer itself, and treatment toxicities may impact adherence and subsequently prognosis. Mittendorf et al reported on patient reported outcomes (PROs) from the phase 3 IMpassion031 trial which showed pCR improvement with atezolizumab/chemotherapy compared to placebo/chemotherapy for neoadjuvant early-stage TNBC. Health-related quality of life items and treatment-related symptoms worsened similarly in both arms during neoadjuvant therapy, and recovered/stabilized in the adjuvant setting. Further exploration of immunotherapy PROs is warranted, as clinical benefit is seen with these agents and they do not appear to negatively impact functioning and patient experience with treatment long-term. Side effect profiles of immunotherapy and standard chemotherapy are different, and design of immunotherapy-specific PROs are desired.

The PRIME 2 10 year results evaluating the role of whole breast irradiation in women ≥65 years with early-stage HR-positive breast cancer receiving hormonal therapy showed RT reduced risk of local recurrence from 9.8% to 0.9% at 10 years (p=0.0008). Patients with low ER tumors had higher 10 year local recurrence rate compared to high ER tumors (18.8% versus 9.2% (p0.007)). Rates of overall survival (80.4% in no RT group vs 81.0% in RT group) and metastasis free survival were similar. A shared decision making approach is key, carefully weighing benefits and risks, considering pathologic features, patient preferences and co-morbidities that may influence endocrine therapy adherence. The impact of molecular subtypes and genomic assays is also being explored to help assess radiation benefit and guide treatment recommendations.

Breast cancer in young women presents unique challenges considering the lifetime period during which diagnosis occurs. Previous studies have supported the safety of pregnancy after breast cancer and guidelines recommend oncofertility counseling in young patients. Blondeaux et al found that breast cancer patients had a 60% lower chance of pregnancy after treatment and were more likely to have complications including low birth weight, small for gestational age, preterm delivery and cesarean section. Although increased risk of congenital abnormalities did not appear to be statistically significant, the HR was 1.63. Importantly, pregnancy after breast cancer did not negatively impact maternal outcomes. This study further supports the safety of pregnancy after breast cancer, highlights the need for close monitoring of pregnancies in these women, and emphasizes the importance of fertility and family planning discussion, which is most optimally provided in a multidisciplinary fashion.

References:

Dent R, Oliveira AM, Isakoff SJ, Im SA, Espié M, Blau S, Saura C, Wongchenko MJ, Xu N, Bradley D, Reilly SJ, Mani A, Kim SB. Final results of the double-blind placebo (PBO)-controlled randomised phase II LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for inoperable locally advanced/metastatic triple-negative breast cancer (mTNBC). Presented during 2020 ESMO breast cancer virtual meeting; May 23-24, 2020. Abstract 139O.

Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020;38:423-433.

Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396:1090-1100.

King-Kallimanis BL, Howie LJ, Roydhouse JK, Singh H, Theoret MR, Blumenthal GM, Kluetz PG. Patient reported outcomes in anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data submitted and future directions. Clin Trials. 2019;16:322-326.

Fodor A, Brombin C, Mangili P, Borroni F, Pasetti M, Tummineri R, Zerbetto F, Longobardi B, Perna L, Dell'Oca I, Deantoni CL, Deli AM, Chiara A, Broggi S, Castriconi R, Esposito PG, Slim N, Passoni P, Baroni S, Villa SL, Rancoita PMV, Fiorino C, Del Vecchio A, Bianchini G, Gentilini OD, Di Serio MS, Di Muzio NG. Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized? Breast. 2020;55:45-54.

Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, Peccatori FA. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47:74-83.

Breast cancer patients treated with curative intent do not often experience symptoms related to the cancer itself, and treatment toxicities may impact adherence and subsequently prognosis. Mittendorf et al reported on patient reported outcomes (PROs) from the phase 3 IMpassion031 trial which showed pCR improvement with atezolizumab/chemotherapy compared to placebo/chemotherapy for neoadjuvant early-stage TNBC. Health-related quality of life items and treatment-related symptoms worsened similarly in both arms during neoadjuvant therapy, and recovered/stabilized in the adjuvant setting. Further exploration of immunotherapy PROs is warranted, as clinical benefit is seen with these agents and they do not appear to negatively impact functioning and patient experience with treatment long-term. Side effect profiles of immunotherapy and standard chemotherapy are different, and design of immunotherapy-specific PROs are desired.

The PRIME 2 10 year results evaluating the role of whole breast irradiation in women ≥65 years with early-stage HR-positive breast cancer receiving hormonal therapy showed RT reduced risk of local recurrence from 9.8% to 0.9% at 10 years (p=0.0008). Patients with low ER tumors had higher 10 year local recurrence rate compared to high ER tumors (18.8% versus 9.2% (p0.007)). Rates of overall survival (80.4% in no RT group vs 81.0% in RT group) and metastasis free survival were similar. A shared decision making approach is key, carefully weighing benefits and risks, considering pathologic features, patient preferences and co-morbidities that may influence endocrine therapy adherence. The impact of molecular subtypes and genomic assays is also being explored to help assess radiation benefit and guide treatment recommendations.

Breast cancer in young women presents unique challenges considering the lifetime period during which diagnosis occurs. Previous studies have supported the safety of pregnancy after breast cancer and guidelines recommend oncofertility counseling in young patients. Blondeaux et al found that breast cancer patients had a 60% lower chance of pregnancy after treatment and were more likely to have complications including low birth weight, small for gestational age, preterm delivery and cesarean section. Although increased risk of congenital abnormalities did not appear to be statistically significant, the HR was 1.63. Importantly, pregnancy after breast cancer did not negatively impact maternal outcomes. This study further supports the safety of pregnancy after breast cancer, highlights the need for close monitoring of pregnancies in these women, and emphasizes the importance of fertility and family planning discussion, which is most optimally provided in a multidisciplinary fashion.

References:

Dent R, Oliveira AM, Isakoff SJ, Im SA, Espié M, Blau S, Saura C, Wongchenko MJ, Xu N, Bradley D, Reilly SJ, Mani A, Kim SB. Final results of the double-blind placebo (PBO)-controlled randomised phase II LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for inoperable locally advanced/metastatic triple-negative breast cancer (mTNBC). Presented during 2020 ESMO breast cancer virtual meeting; May 23-24, 2020. Abstract 139O.

Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020;38:423-433.

Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396:1090-1100.

King-Kallimanis BL, Howie LJ, Roydhouse JK, Singh H, Theoret MR, Blumenthal GM, Kluetz PG. Patient reported outcomes in anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data submitted and future directions. Clin Trials. 2019;16:322-326.

Fodor A, Brombin C, Mangili P, Borroni F, Pasetti M, Tummineri R, Zerbetto F, Longobardi B, Perna L, Dell'Oca I, Deantoni CL, Deli AM, Chiara A, Broggi S, Castriconi R, Esposito PG, Slim N, Passoni P, Baroni S, Villa SL, Rancoita PMV, Fiorino C, Del Vecchio A, Bianchini G, Gentilini OD, Di Serio MS, Di Muzio NG. Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized? Breast. 2020;55:45-54.

Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, Peccatori FA. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47:74-83.

Key clinical point: Omitting adjuvant radiotherapy may be an option for some older women with low-risk, hormone receptor-positive breast cancer who are receiving appropriate endocrine treatment.

Major finding: The 10-year rate of ipsilateral recurrence was lower with radiotherapy than without (0.9% vs. 9.8%, P = .00008), but there was no significant between-arm difference in 10-year overall survival (81.0% and 80.4%, respectively; P = .68).

Study details: A phase 3, randomized trial of 1,326 women age 65 and older with hormone receptor–positive, low-risk early breast cancer undergoing breast-conserving surgery and receiving adjuvant endocrine therapy with or without whole breast irradiation (40-50 Gy in 15-25 fractions).

Disclosures: The study was funded by the Chief Scientist Office (Scottish Government) and the Breast Cancer Institute at the Western General Hospital in Edinburgh, Scotland. Dr. Kunkler did not have any disclosures.

Source: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.

Key clinical point: Omitting adjuvant radiotherapy may be an option for some older women with low-risk, hormone receptor-positive breast cancer who are receiving appropriate endocrine treatment.

Major finding: The 10-year rate of ipsilateral recurrence was lower with radiotherapy than without (0.9% vs. 9.8%, P = .00008), but there was no significant between-arm difference in 10-year overall survival (81.0% and 80.4%, respectively; P = .68).

Study details: A phase 3, randomized trial of 1,326 women age 65 and older with hormone receptor–positive, low-risk early breast cancer undergoing breast-conserving surgery and receiving adjuvant endocrine therapy with or without whole breast irradiation (40-50 Gy in 15-25 fractions).

Disclosures: The study was funded by the Chief Scientist Office (Scottish Government) and the Breast Cancer Institute at the Western General Hospital in Edinburgh, Scotland. Dr. Kunkler did not have any disclosures.

Source: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.

Key clinical point: Omitting adjuvant radiotherapy may be an option for some older women with low-risk, hormone receptor-positive breast cancer who are receiving appropriate endocrine treatment.

Major finding: The 10-year rate of ipsilateral recurrence was lower with radiotherapy than without (0.9% vs. 9.8%, P = .00008), but there was no significant between-arm difference in 10-year overall survival (81.0% and 80.4%, respectively; P = .68).

Study details: A phase 3, randomized trial of 1,326 women age 65 and older with hormone receptor–positive, low-risk early breast cancer undergoing breast-conserving surgery and receiving adjuvant endocrine therapy with or without whole breast irradiation (40-50 Gy in 15-25 fractions).

Disclosures: The study was funded by the Chief Scientist Office (Scottish Government) and the Breast Cancer Institute at the Western General Hospital in Edinburgh, Scotland. Dr. Kunkler did not have any disclosures.

Source: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.

Key clinical point: One year of palbociclib added to endocrine therapy after neoadjuvant chemotherapy did not improve invasive disease-free survival when compared with placebo plus endocrine therapy in women with hormone receptor–positive, HER2-negative primary breast cancer.

Major finding: The 4-year invasive disease-free survival rate was 73.0% for palbociclib and 72.4% for placebo (hazard ratio, 0.93; P = .525).

Study details: A phase 3 trial of 1,250 women with hormone receptor–positive, HER2-negative primary breast cancer who were at high risk of relapse after neoadjuvant chemotherapy.

Disclosures: The trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study, relationships with other companies outside the submitted work, a pending patent for a method to predict response to anti-HER2–containing therapy and/or chemotherapy, and a relationship with Medscape, which is owned by the same company as MDedge.

Source: Loibl S et al. SABCS 2020, Abstract GS1-02.

Key clinical point: One year of palbociclib added to endocrine therapy after neoadjuvant chemotherapy did not improve invasive disease-free survival when compared with placebo plus endocrine therapy in women with hormone receptor–positive, HER2-negative primary breast cancer.

Major finding: The 4-year invasive disease-free survival rate was 73.0% for palbociclib and 72.4% for placebo (hazard ratio, 0.93; P = .525).

Study details: A phase 3 trial of 1,250 women with hormone receptor–positive, HER2-negative primary breast cancer who were at high risk of relapse after neoadjuvant chemotherapy.

Disclosures: The trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study, relationships with other companies outside the submitted work, a pending patent for a method to predict response to anti-HER2–containing therapy and/or chemotherapy, and a relationship with Medscape, which is owned by the same company as MDedge.

Source: Loibl S et al. SABCS 2020, Abstract GS1-02.

Key clinical point: One year of palbociclib added to endocrine therapy after neoadjuvant chemotherapy did not improve invasive disease-free survival when compared with placebo plus endocrine therapy in women with hormone receptor–positive, HER2-negative primary breast cancer.

Major finding: The 4-year invasive disease-free survival rate was 73.0% for palbociclib and 72.4% for placebo (hazard ratio, 0.93; P = .525).

Study details: A phase 3 trial of 1,250 women with hormone receptor–positive, HER2-negative primary breast cancer who were at high risk of relapse after neoadjuvant chemotherapy.

Disclosures: The trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study, relationships with other companies outside the submitted work, a pending patent for a method to predict response to anti-HER2–containing therapy and/or chemotherapy, and a relationship with Medscape, which is owned by the same company as MDedge.

Source: Loibl S et al. SABCS 2020, Abstract GS1-02.

Key clinical point: Diet may influence breast cancer outcomes.

Major finding: Women who adhered to the healthiest diet had a 31% lower risk for all-cause mortality versus women in the lowest tier for dietary health.

Study details: A retrospective study of 8,320 women with breast cancer in the first and second Nurses’ Health Studies.

Disclosures: This research was supported, in part, by grants from the National Cancer Institute, Breast Cancer Research Foundations, and Susan G. Komen Breast Cancer Foundations. Dr. Wang reported no relevant conflicts of interest.

Source: Wang T et al. SABCS 2020, Abstract GS2-09.

Key clinical point: Diet may influence breast cancer outcomes.

Major finding: Women who adhered to the healthiest diet had a 31% lower risk for all-cause mortality versus women in the lowest tier for dietary health.

Study details: A retrospective study of 8,320 women with breast cancer in the first and second Nurses’ Health Studies.

Disclosures: This research was supported, in part, by grants from the National Cancer Institute, Breast Cancer Research Foundations, and Susan G. Komen Breast Cancer Foundations. Dr. Wang reported no relevant conflicts of interest.

Source: Wang T et al. SABCS 2020, Abstract GS2-09.

Key clinical point: Diet may influence breast cancer outcomes.

Major finding: Women who adhered to the healthiest diet had a 31% lower risk for all-cause mortality versus women in the lowest tier for dietary health.

Study details: A retrospective study of 8,320 women with breast cancer in the first and second Nurses’ Health Studies.

Disclosures: This research was supported, in part, by grants from the National Cancer Institute, Breast Cancer Research Foundations, and Susan G. Komen Breast Cancer Foundations. Dr. Wang reported no relevant conflicts of interest.

Source: Wang T et al. SABCS 2020, Abstract GS2-09.

Key clinical point: Breast cancer survivors are less likely to conceive and have more complications when they do, but pregnancy does not increase the risk of cancer recurrence, a review suggests.

Major finding: Relative to the general population, breast cancer survivors were 60% less likely to become pregnant, and they had higher odds of complications such as preterm birth (45% higher) and low birth weight (50% higher), but their risk of cancer recurrence was not increased.

Study details: A systematic review and meta-analysis using data from 39 studies that included a total of 114,573 breast cancer patients and 8,093,401 women from the general population.

Disclosures: The study was funded by the Italian Ministry of Health and the Italian Association for Cancer Research. Dr. Blondeaux disclosed no conflicts of interest.

Source: Blondeaux et al. SABCS 2020, Abstract GS3-09.

Key clinical point: Breast cancer survivors are less likely to conceive and have more complications when they do, but pregnancy does not increase the risk of cancer recurrence, a review suggests.

Major finding: Relative to the general population, breast cancer survivors were 60% less likely to become pregnant, and they had higher odds of complications such as preterm birth (45% higher) and low birth weight (50% higher), but their risk of cancer recurrence was not increased.

Study details: A systematic review and meta-analysis using data from 39 studies that included a total of 114,573 breast cancer patients and 8,093,401 women from the general population.

Disclosures: The study was funded by the Italian Ministry of Health and the Italian Association for Cancer Research. Dr. Blondeaux disclosed no conflicts of interest.

Source: Blondeaux et al. SABCS 2020, Abstract GS3-09.

Key clinical point: Breast cancer survivors are less likely to conceive and have more complications when they do, but pregnancy does not increase the risk of cancer recurrence, a review suggests.

Major finding: Relative to the general population, breast cancer survivors were 60% less likely to become pregnant, and they had higher odds of complications such as preterm birth (45% higher) and low birth weight (50% higher), but their risk of cancer recurrence was not increased.

Study details: A systematic review and meta-analysis using data from 39 studies that included a total of 114,573 breast cancer patients and 8,093,401 women from the general population.

Disclosures: The study was funded by the Italian Ministry of Health and the Italian Association for Cancer Research. Dr. Blondeaux disclosed no conflicts of interest.

Source: Blondeaux et al. SABCS 2020, Abstract GS3-09.

Key clinical point: Adding immunotherapy to chemotherapy for early triple-negative breast cancer did not increase symptom burden.

Major finding: Health-related quality-of-life measures were similar whether patients received chemotherapy with atezolizumab or with placebo. For example, mean physical function scores were about 90% in both treatment arms at baseline, dropped to about 65% in each arm by cycle 5, and rebounded to about 80% by cycle 7.

Study details: Exploratory patient-reported outcomes from 328 patients in the phase 3 IMpassion031 trial.

Disclosures: IMpassion031 is sponsored by F. Hoffman-LaRoche. Dr. Mittendorf disclosed relationships with Roche/Genentech, GlaxoSmithKline, Physicians’ Education Resource, AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, TapImmune, EMD Serono, Galena Biopharma, Bristol Myers Squibb, and Lilly.

Source: Mittendorf E at al. SABCS 2020, Abstract GS3-02.

Key clinical point: Adding immunotherapy to chemotherapy for early triple-negative breast cancer did not increase symptom burden.

Major finding: Health-related quality-of-life measures were similar whether patients received chemotherapy with atezolizumab or with placebo. For example, mean physical function scores were about 90% in both treatment arms at baseline, dropped to about 65% in each arm by cycle 5, and rebounded to about 80% by cycle 7.

Study details: Exploratory patient-reported outcomes from 328 patients in the phase 3 IMpassion031 trial.

Disclosures: IMpassion031 is sponsored by F. Hoffman-LaRoche. Dr. Mittendorf disclosed relationships with Roche/Genentech, GlaxoSmithKline, Physicians’ Education Resource, AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, TapImmune, EMD Serono, Galena Biopharma, Bristol Myers Squibb, and Lilly.

Source: Mittendorf E at al. SABCS 2020, Abstract GS3-02.

Key clinical point: Adding immunotherapy to chemotherapy for early triple-negative breast cancer did not increase symptom burden.

Major finding: Health-related quality-of-life measures were similar whether patients received chemotherapy with atezolizumab or with placebo. For example, mean physical function scores were about 90% in both treatment arms at baseline, dropped to about 65% in each arm by cycle 5, and rebounded to about 80% by cycle 7.

Study details: Exploratory patient-reported outcomes from 328 patients in the phase 3 IMpassion031 trial.

Disclosures: IMpassion031 is sponsored by F. Hoffman-LaRoche. Dr. Mittendorf disclosed relationships with Roche/Genentech, GlaxoSmithKline, Physicians’ Education Resource, AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, TapImmune, EMD Serono, Galena Biopharma, Bristol Myers Squibb, and Lilly.

Source: Mittendorf E at al. SABCS 2020, Abstract GS3-02.

Key clinical point: Comorbid depression, sleep disorders, or their combination is associated with early mortality in women with breast cancer.

Major finding: Depression (adjusted hazard ratio [aHR], 1.44; 95% confidence interval [CI], 1.17-1.78) and sleep disorders (aHR, 1.37; 95% CI, 1.02-1.84) were significantly associated with an increase in 5-year mortality. For the combination of depression and sleep disorders, aHR was 1.75 (95% CI: 1.17-2.60).

Study details: The data come from a retrospective cohort study of women diagnosed with breast cancer (2008-2012) in 1 of 200 general practices in the UK (n = 6,656; age, 18-80 years).

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Bach L et al. J Psychiatr Res. 2020 Nov 23. doi: 10.1016/j.jpsychires.2020.11.036.

Key clinical point: Comorbid depression, sleep disorders, or their combination is associated with early mortality in women with breast cancer.

Major finding: Depression (adjusted hazard ratio [aHR], 1.44; 95% confidence interval [CI], 1.17-1.78) and sleep disorders (aHR, 1.37; 95% CI, 1.02-1.84) were significantly associated with an increase in 5-year mortality. For the combination of depression and sleep disorders, aHR was 1.75 (95% CI: 1.17-2.60).

Study details: The data come from a retrospective cohort study of women diagnosed with breast cancer (2008-2012) in 1 of 200 general practices in the UK (n = 6,656; age, 18-80 years).

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Bach L et al. J Psychiatr Res. 2020 Nov 23. doi: 10.1016/j.jpsychires.2020.11.036.

Key clinical point: Comorbid depression, sleep disorders, or their combination is associated with early mortality in women with breast cancer.

Major finding: Depression (adjusted hazard ratio [aHR], 1.44; 95% confidence interval [CI], 1.17-1.78) and sleep disorders (aHR, 1.37; 95% CI, 1.02-1.84) were significantly associated with an increase in 5-year mortality. For the combination of depression and sleep disorders, aHR was 1.75 (95% CI: 1.17-2.60).

Study details: The data come from a retrospective cohort study of women diagnosed with breast cancer (2008-2012) in 1 of 200 general practices in the UK (n = 6,656; age, 18-80 years).

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Bach L et al. J Psychiatr Res. 2020 Nov 23. doi: 10.1016/j.jpsychires.2020.11.036.

Key clinical point: Underweight appears as an independent negative prognostic factor for both overall survival (OS) and first-line progression-free survival (PFS) in women with metastatic breast cancer (MBC). In contrast, overweight and obesity are not associated with poorer outcomes.

Major finding: The median OS was 47.4 months (median follow-up, 48.6 months). Underweight (body mass index [BMI], less than 18.5 kg/m²) showed an independent association with worse OS (median OS, 33 months; hazard ratio [HR ], 1.14; 95% confidence interval [CI], 1.02-1.28) and first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight (BMI, 25.0-29.9 kg/m²) or obesity (BMI, 30.0 kg/m² or higher) had no impact on OS.

Study details: This study evaluated the impact of BMI on survival outcomes among patients with metastatic breast cancer (n = 12,999) in the ESME-MBC cohort (median BMI, 24.9 kg/m²; 20% of women were obese and 5% underweight).

Disclosures: The ESME MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai, and Daiichi Sankyo). Dr. K Saleh had no disclosures. Some of his coinvestigators reported ties with pharmaceutical companies.

Source: Saleh K et al. Breast. 2020 Dec 1. doi: 10.1016/j.breast.2020.11.014.

Key clinical point: Underweight appears as an independent negative prognostic factor for both overall survival (OS) and first-line progression-free survival (PFS) in women with metastatic breast cancer (MBC). In contrast, overweight and obesity are not associated with poorer outcomes.

Major finding: The median OS was 47.4 months (median follow-up, 48.6 months). Underweight (body mass index [BMI], less than 18.5 kg/m²) showed an independent association with worse OS (median OS, 33 months; hazard ratio [HR ], 1.14; 95% confidence interval [CI], 1.02-1.28) and first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight (BMI, 25.0-29.9 kg/m²) or obesity (BMI, 30.0 kg/m² or higher) had no impact on OS.

Study details: This study evaluated the impact of BMI on survival outcomes among patients with metastatic breast cancer (n = 12,999) in the ESME-MBC cohort (median BMI, 24.9 kg/m²; 20% of women were obese and 5% underweight).

Disclosures: The ESME MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai, and Daiichi Sankyo). Dr. K Saleh had no disclosures. Some of his coinvestigators reported ties with pharmaceutical companies.

Source: Saleh K et al. Breast. 2020 Dec 1. doi: 10.1016/j.breast.2020.11.014.

Key clinical point: Underweight appears as an independent negative prognostic factor for both overall survival (OS) and first-line progression-free survival (PFS) in women with metastatic breast cancer (MBC). In contrast, overweight and obesity are not associated with poorer outcomes.

Major finding: The median OS was 47.4 months (median follow-up, 48.6 months). Underweight (body mass index [BMI], less than 18.5 kg/m²) showed an independent association with worse OS (median OS, 33 months; hazard ratio [HR ], 1.14; 95% confidence interval [CI], 1.02-1.28) and first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight (BMI, 25.0-29.9 kg/m²) or obesity (BMI, 30.0 kg/m² or higher) had no impact on OS.

Study details: This study evaluated the impact of BMI on survival outcomes among patients with metastatic breast cancer (n = 12,999) in the ESME-MBC cohort (median BMI, 24.9 kg/m²; 20% of women were obese and 5% underweight).

Disclosures: The ESME MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai, and Daiichi Sankyo). Dr. K Saleh had no disclosures. Some of his coinvestigators reported ties with pharmaceutical companies.

Source: Saleh K et al. Breast. 2020 Dec 1. doi: 10.1016/j.breast.2020.11.014.

Key clinical point: Circulating tumor cell (CTC) count-driven first-line therapy (chemotherapy or endocrine therapy) is noninferior to clinician choice-driven first-line therapy for progression-free survival (PFS) in hormone receptor (HR)-positive/HER2-negative metastatic breast cancer.

Major finding: The median PFS was 15.5 (95% confidence interval [CI], 12.7-17.3) months in the CTC-guided group and 13.9 (95% CI, 12.2-16.3) months in the clinician-driven choice group. The primary end point (PFS in the per-protocol population with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio [HR]) was met with an HR of 0.94 (90% CI, 0.81-1.09). Overall survival was also noninferior with CTC guidance (HR, 0.91; 95% CI, 0.71-1.16).

Study details: In this phase 3 STIC CTC trial, 755 women with HR-positive/HER2-negative metastatic breast cancer were randomly assigned (1:1) to receive a CTC-driven first-line therapy (chemotherapy if 5 CTCs or more/7.5 mL; endocrine therapy if less than 5 CTCs/7.5 mL) or clinician choice-driven first-line therapy (chemotherapy or endocrine therapy) at 17 French centers.

Disclosures: The study was funded by Institut Curie, the French National Cancer Institute as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011, and Menarini Silicon Biosystems. The lead author reported receiving grants and nonfinancial support from Menarini Silicon Biosystems during the conduct of the study.

Source: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.

Key clinical point: Circulating tumor cell (CTC) count-driven first-line therapy (chemotherapy or endocrine therapy) is noninferior to clinician choice-driven first-line therapy for progression-free survival (PFS) in hormone receptor (HR)-positive/HER2-negative metastatic breast cancer.

Major finding: The median PFS was 15.5 (95% confidence interval [CI], 12.7-17.3) months in the CTC-guided group and 13.9 (95% CI, 12.2-16.3) months in the clinician-driven choice group. The primary end point (PFS in the per-protocol population with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio [HR]) was met with an HR of 0.94 (90% CI, 0.81-1.09). Overall survival was also noninferior with CTC guidance (HR, 0.91; 95% CI, 0.71-1.16).

Study details: In this phase 3 STIC CTC trial, 755 women with HR-positive/HER2-negative metastatic breast cancer were randomly assigned (1:1) to receive a CTC-driven first-line therapy (chemotherapy if 5 CTCs or more/7.5 mL; endocrine therapy if less than 5 CTCs/7.5 mL) or clinician choice-driven first-line therapy (chemotherapy or endocrine therapy) at 17 French centers.

Disclosures: The study was funded by Institut Curie, the French National Cancer Institute as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011, and Menarini Silicon Biosystems. The lead author reported receiving grants and nonfinancial support from Menarini Silicon Biosystems during the conduct of the study.

Source: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.

Key clinical point: Circulating tumor cell (CTC) count-driven first-line therapy (chemotherapy or endocrine therapy) is noninferior to clinician choice-driven first-line therapy for progression-free survival (PFS) in hormone receptor (HR)-positive/HER2-negative metastatic breast cancer.

Major finding: The median PFS was 15.5 (95% confidence interval [CI], 12.7-17.3) months in the CTC-guided group and 13.9 (95% CI, 12.2-16.3) months in the clinician-driven choice group. The primary end point (PFS in the per-protocol population with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio [HR]) was met with an HR of 0.94 (90% CI, 0.81-1.09). Overall survival was also noninferior with CTC guidance (HR, 0.91; 95% CI, 0.71-1.16).

Study details: In this phase 3 STIC CTC trial, 755 women with HR-positive/HER2-negative metastatic breast cancer were randomly assigned (1:1) to receive a CTC-driven first-line therapy (chemotherapy if 5 CTCs or more/7.5 mL; endocrine therapy if less than 5 CTCs/7.5 mL) or clinician choice-driven first-line therapy (chemotherapy or endocrine therapy) at 17 French centers.

Disclosures: The study was funded by Institut Curie, the French National Cancer Institute as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011, and Menarini Silicon Biosystems. The lead author reported receiving grants and nonfinancial support from Menarini Silicon Biosystems during the conduct of the study.

Source: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.