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JCO Article Insights: Elderly Patients Receiving Chemotherapy for Early-Stage Breast Cancer

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In this JCO Article Insights episode, Davide Soldato summarizes two articles from the January 10th, 2023 Journal of Clinical Oncology issue: “Low-Intensity Chemotherapy for Early Breast Cancer in Older Women: Results From the Prospective Multicenter HOPE Trial” and “Inflammation and Clinical Decline After Adjuvant Chemotherapy: Results From the Hurria Older Patients Prospective Study .” Both articles report on clinical outcomes of elderly patients treated with chemotherapy for early-stage breast cancer.

TRANSCRIPT

Davide Soldato: Thank you for joining JCO Article Insights. I'm Davide Soldato. Today I will be providing summaries for two different articles focused on elderly patients treated for early-stage breast cancer. Both articles are reported from the Hurria Older Patients With Breast Cancer Study. This study is also known as the HOPE Study, and it was a multicenter, prospective, study of patients aged 65 years and older treated with current standard (Neo)adjuvant chemotherapy regimens for early-stage breast cancer. The study captured several detailed geriatric clinical and treatment data from 500 patients that were recruited between September 2011 and May 2017 in 16 sites across the United States.

The first article is titled ‘Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women’. In this article, Dr. Sedrak and colleagues used data from the HOPE Study to investigate the incidence of chemotherapy administration with low relative dose intensity, associated risk factors, and relationship with survival outcomes. Previous data already showed that the receipt of chemotherapy with a low relative dose intensity is associated with inferior survival outcomes, and the commonly used threshold to define a low relative dose intensity is 85%. And this same threshold was used inside of the study that I am reporting. Elderly patients that are treated with chemotherapy are at higher risk of receiving chemotherapy with low relative dose intensity because of toxicity. However, previous data on the topic was mainly retrospective in nature and reported heterogeneous rates of low relative dose intensity up to 75%. And also, little information was available on risk factors and on the impact on survival outcomes. So, considering the paucity and the quality of the previous data and the potential clinical implication for survival outcomes, results of the HOPE Study are extremely relevant to clinical practice as they provide novel insight on the topic from a prospective multicenter study.

In the analysis that was reported in the January issue of JCO, the authors excluded patients with HER-2 positive disease, those receiving nonstandard chemotherapy regimens, and those with upfront chemotherapy dose reduction. The final analytic cohort included 322 patients with a median age of 70 years, 44% with stage II, and 22% with stage III disease. Docetaxel and cyclophosphamide, and anthracycline-based chemotherapy, and this one, either alone or with subsequent paclitaxel, were the most commonly used chemotherapy regimens. Additionally, 85% of patients received a primary prophylaxis with G-CSF. Relative dose intensity was variable in the study. More than half of the patients received full course chemotherapy with 100% relative dose intensity. However, the incidence of low relative dose intensity in the HOPE study was still 21%, thus identifying a subset of patients who received chemotherapy with a suboptimal dose intensity. The rates of low relative dose intensity were higher for patients receiving either anthracycline-based chemotherapy and those with a planned treatment duration over 12 weeks.

The authors developed a multivariable logistic regression model with stepwise selection to identify risk factors associated with low relative dose intensity. The results of this analysis showed that an age higher than 76 years, administration of anthracycline and CMF-based regimens, and a physician-rated Karnofsky Performance Status under 90 were associated with higher risk of low relative dose intensity ranging from 3 to 5 times greater compared to reference categories. Then the authors realized another model where they used the previously mentioned three variables, but they also adjusted for relevant clinical characteristics, including age, stage, liver and renal function, and also previous cardiovascular disease. And in this model, the three variables that were observed previously— age, type of chemotherapy, and Karnofsky Performance Status—remained significantly associated with higher risk of receiving chemotherapy with a low relative dose intensity.

Finally, the Authors evaluated the association between a low relative dose intensity and survival outcomes, specifically breast cancer-specific mortality, non-breast cancer-specific mortality, and overall survival. Patients who received the chemotherapy with a low relative dose intensity had a significantly lower overall survival, and this association persisted even after excluding patients older than 76 years. A higher risk of both breast cancer and non-breast cancer mortality was observed in patients with low relative dose intensity chemotherapy. However, the number of cause-specific events was too low to obtain statistical significance for both these endpoints.

In conclusion, the study by Dr. Sedrak and colleagues provides several relevant information for clinical practice. First, the HOPE study demonstrates that the administration of chemotherapy to elderly patients while maintaining an appropriate relative dose intensity is feasible. However, 1 in 5 patients received chemotherapy with a low relative dose intensity. So the results of this study reinforced the need to identify upfront patients most likely to require dose reduction. And these patients should be proactively supported during the administration of chemotherapy to ensure that appropriate toxicity management can reduce the risk of low relative dose intensity.

Second, in the study, the authors observed a significant association between a low relative dose intensity and the CARG and CARG-BC scores. These scores were previously validated to predict chemotherapy toxicity. The presence of this association is important because it suggests that these validated scores can be used routinely in clinical practice to identify patients that might benefit from a comprehensive geriatric assessment to optimize comorbidities treatments and assure optimal delivery of chemotherapy.

Finally, longer follow-up will provide the opportunity to establish if the higher mortality that was observed in the HOPE study in patients receiving chemotherapy with a low relative dose intensity is consequent to the low chemotherapy efficacy or to a clinical decline that might be consequent to chemotherapy itself.

I will now move to the second article titled ‘Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults With Breast Cancer’. This article was published by Dr. Ji and colleagues, and it describes a secondary analysis of the HOPE study. In this specific manuscript, the authors wanted to evaluate the potential predictive role of baseline inflammatory biomarkers on the risk of clinical decline after administration of chemotherapy. In the HOPE study, the authors collected information on frailty stages, pre and post-chemotherapy using the Deficit-Accumulation Index (DAI): this is a 50-item scale that evaluates deficits in physical activity of daily living, instrumental activities of daily living, psychosocial status, nutrition, frequency of falls, number of medications, comorbid conditions, social support, and laboratory values. The inflammatory biomarkers that were evaluated in the current study were CRP and IL-6, and their levels were determined on pre-chemotherapy blood specimens. Using the deficit accumulation index score, patients were categorized pre-chemotherapy as being robust, pre-frail, or frail; this is important because previous studies already demonstrated that there is a significant association between this categorization and morbidity and mortality outcomes in older adults.

The primary outcome of the study was a chemotherapy-induced clinical decline that was defined as a decline from a robust stage pre-chemotherapy to a pre-frail or frail status after chemotherapy. The overall analytic cohorts included 295 robust women. The median age was 69, 62% of patients had stage II or III disease, median number of comorbidities was 1.9, and mean BMI was 28.5. One in 4 older women included in the study experienced a chemotherapy-induced decline in frailty status, so this means that they transitioned from a robust status pre-chemotherapy to a pre-frail or frail status after chemotherapy. This decline in frailty status was more frequent among patients with a higher BMI, those with more comorbidities, and those with stage II and III disease.

Additionally, the patients who experienced chemotherapy-induced decline had higher baseline levels of both IL-6 and CRP. Univariate analysis also showed that patients with high IL-6 and CRP had a threefold higher risk of experiencing chemotherapy-induced decline in frailty stages. This association between higher inflammation and the decline in frailty status remained significant in a multivariable logistic regression analysis that was adjusted for relevant clinical and demographic characteristics, including age, stage, race, education, BMI, breast cancer surgery, anti-inflammatory medication, and number of comorbidities. Specifically, the results of these models showed that patients who had both high CRP and IL-6 at baseline had a threefold higher risk of experiencing a decline in frailty status.

So, in conclusion, this study shows a significant association between systemic inflammation and a decline in frailty status in elderly patients receiving chemotherapy for early-stage breast cancer. From a biological perspective, these higher levels of systemic inflammation might be a direct byproduct of a more advanced biological aging following the accumulation of senescent cells. There are several intriguing future perspectives that come from this study. First, if validated in additional cohorts, these findings might lead to higher treatment personalization thanks to the identification of patients at risk of clinical decline based on clinical characteristics but also on systemic inflammation. And these patients could be then proactively supported during chemotherapy to try and reduce the appearance of the clinical decline. Second, we know that inflammation is a potentially targetable pathway, and previous data obtained in breast cancer patients showed the potential of behavioral, exercise, and dietary interventions in modulating systemic inflammation. So, based on this new information, if validated in additional cohorts, future research should then evaluate if this interventions can be used to treat and eventually prevent the decline in frailty status in patients with high baseline systemic inflammation before receiving chemotherapy.

This is Davide Soldato in this episode of JCO Article Insights. We discussed two publications: ‘Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women: Results from the Prospective Multicenter HOPE Trial’, and the second one, ‘Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults with Breast cancer: Results from the Hurria Older Patients Prospective Study’.

Thank you for your attention, and stay tuned for the next episode.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Like, share and subscribe so you never miss an episode and leave a rating or review.

Articles

Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women

Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults With Breast Cancer

Find more articles from the January 10 issue.

  continue reading

398 afleveringen

Artwork
iconDelen
 
Manage episode 353913908 series 2932803
Inhoud geleverd door Journals Online Team and American Society of Clinical Oncology (ASCO). Alle podcastinhoud, inclusief afleveringen, afbeeldingen en podcastbeschrijvingen, wordt rechtstreeks geüpload en geleverd door Journals Online Team and American Society of Clinical Oncology (ASCO) of hun podcastplatformpartner. Als u denkt dat iemand uw auteursrechtelijk beschermde werk zonder uw toestemming gebruikt, kunt u het hier beschreven proces https://nl.player.fm/legal volgen.

In this JCO Article Insights episode, Davide Soldato summarizes two articles from the January 10th, 2023 Journal of Clinical Oncology issue: “Low-Intensity Chemotherapy for Early Breast Cancer in Older Women: Results From the Prospective Multicenter HOPE Trial” and “Inflammation and Clinical Decline After Adjuvant Chemotherapy: Results From the Hurria Older Patients Prospective Study .” Both articles report on clinical outcomes of elderly patients treated with chemotherapy for early-stage breast cancer.

TRANSCRIPT

Davide Soldato: Thank you for joining JCO Article Insights. I'm Davide Soldato. Today I will be providing summaries for two different articles focused on elderly patients treated for early-stage breast cancer. Both articles are reported from the Hurria Older Patients With Breast Cancer Study. This study is also known as the HOPE Study, and it was a multicenter, prospective, study of patients aged 65 years and older treated with current standard (Neo)adjuvant chemotherapy regimens for early-stage breast cancer. The study captured several detailed geriatric clinical and treatment data from 500 patients that were recruited between September 2011 and May 2017 in 16 sites across the United States.

The first article is titled ‘Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women’. In this article, Dr. Sedrak and colleagues used data from the HOPE Study to investigate the incidence of chemotherapy administration with low relative dose intensity, associated risk factors, and relationship with survival outcomes. Previous data already showed that the receipt of chemotherapy with a low relative dose intensity is associated with inferior survival outcomes, and the commonly used threshold to define a low relative dose intensity is 85%. And this same threshold was used inside of the study that I am reporting. Elderly patients that are treated with chemotherapy are at higher risk of receiving chemotherapy with low relative dose intensity because of toxicity. However, previous data on the topic was mainly retrospective in nature and reported heterogeneous rates of low relative dose intensity up to 75%. And also, little information was available on risk factors and on the impact on survival outcomes. So, considering the paucity and the quality of the previous data and the potential clinical implication for survival outcomes, results of the HOPE Study are extremely relevant to clinical practice as they provide novel insight on the topic from a prospective multicenter study.

In the analysis that was reported in the January issue of JCO, the authors excluded patients with HER-2 positive disease, those receiving nonstandard chemotherapy regimens, and those with upfront chemotherapy dose reduction. The final analytic cohort included 322 patients with a median age of 70 years, 44% with stage II, and 22% with stage III disease. Docetaxel and cyclophosphamide, and anthracycline-based chemotherapy, and this one, either alone or with subsequent paclitaxel, were the most commonly used chemotherapy regimens. Additionally, 85% of patients received a primary prophylaxis with G-CSF. Relative dose intensity was variable in the study. More than half of the patients received full course chemotherapy with 100% relative dose intensity. However, the incidence of low relative dose intensity in the HOPE study was still 21%, thus identifying a subset of patients who received chemotherapy with a suboptimal dose intensity. The rates of low relative dose intensity were higher for patients receiving either anthracycline-based chemotherapy and those with a planned treatment duration over 12 weeks.

The authors developed a multivariable logistic regression model with stepwise selection to identify risk factors associated with low relative dose intensity. The results of this analysis showed that an age higher than 76 years, administration of anthracycline and CMF-based regimens, and a physician-rated Karnofsky Performance Status under 90 were associated with higher risk of low relative dose intensity ranging from 3 to 5 times greater compared to reference categories. Then the authors realized another model where they used the previously mentioned three variables, but they also adjusted for relevant clinical characteristics, including age, stage, liver and renal function, and also previous cardiovascular disease. And in this model, the three variables that were observed previously— age, type of chemotherapy, and Karnofsky Performance Status—remained significantly associated with higher risk of receiving chemotherapy with a low relative dose intensity.

Finally, the Authors evaluated the association between a low relative dose intensity and survival outcomes, specifically breast cancer-specific mortality, non-breast cancer-specific mortality, and overall survival. Patients who received the chemotherapy with a low relative dose intensity had a significantly lower overall survival, and this association persisted even after excluding patients older than 76 years. A higher risk of both breast cancer and non-breast cancer mortality was observed in patients with low relative dose intensity chemotherapy. However, the number of cause-specific events was too low to obtain statistical significance for both these endpoints.

In conclusion, the study by Dr. Sedrak and colleagues provides several relevant information for clinical practice. First, the HOPE study demonstrates that the administration of chemotherapy to elderly patients while maintaining an appropriate relative dose intensity is feasible. However, 1 in 5 patients received chemotherapy with a low relative dose intensity. So the results of this study reinforced the need to identify upfront patients most likely to require dose reduction. And these patients should be proactively supported during the administration of chemotherapy to ensure that appropriate toxicity management can reduce the risk of low relative dose intensity.

Second, in the study, the authors observed a significant association between a low relative dose intensity and the CARG and CARG-BC scores. These scores were previously validated to predict chemotherapy toxicity. The presence of this association is important because it suggests that these validated scores can be used routinely in clinical practice to identify patients that might benefit from a comprehensive geriatric assessment to optimize comorbidities treatments and assure optimal delivery of chemotherapy.

Finally, longer follow-up will provide the opportunity to establish if the higher mortality that was observed in the HOPE study in patients receiving chemotherapy with a low relative dose intensity is consequent to the low chemotherapy efficacy or to a clinical decline that might be consequent to chemotherapy itself.

I will now move to the second article titled ‘Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults With Breast Cancer’. This article was published by Dr. Ji and colleagues, and it describes a secondary analysis of the HOPE study. In this specific manuscript, the authors wanted to evaluate the potential predictive role of baseline inflammatory biomarkers on the risk of clinical decline after administration of chemotherapy. In the HOPE study, the authors collected information on frailty stages, pre and post-chemotherapy using the Deficit-Accumulation Index (DAI): this is a 50-item scale that evaluates deficits in physical activity of daily living, instrumental activities of daily living, psychosocial status, nutrition, frequency of falls, number of medications, comorbid conditions, social support, and laboratory values. The inflammatory biomarkers that were evaluated in the current study were CRP and IL-6, and their levels were determined on pre-chemotherapy blood specimens. Using the deficit accumulation index score, patients were categorized pre-chemotherapy as being robust, pre-frail, or frail; this is important because previous studies already demonstrated that there is a significant association between this categorization and morbidity and mortality outcomes in older adults.

The primary outcome of the study was a chemotherapy-induced clinical decline that was defined as a decline from a robust stage pre-chemotherapy to a pre-frail or frail status after chemotherapy. The overall analytic cohorts included 295 robust women. The median age was 69, 62% of patients had stage II or III disease, median number of comorbidities was 1.9, and mean BMI was 28.5. One in 4 older women included in the study experienced a chemotherapy-induced decline in frailty status, so this means that they transitioned from a robust status pre-chemotherapy to a pre-frail or frail status after chemotherapy. This decline in frailty status was more frequent among patients with a higher BMI, those with more comorbidities, and those with stage II and III disease.

Additionally, the patients who experienced chemotherapy-induced decline had higher baseline levels of both IL-6 and CRP. Univariate analysis also showed that patients with high IL-6 and CRP had a threefold higher risk of experiencing chemotherapy-induced decline in frailty stages. This association between higher inflammation and the decline in frailty status remained significant in a multivariable logistic regression analysis that was adjusted for relevant clinical and demographic characteristics, including age, stage, race, education, BMI, breast cancer surgery, anti-inflammatory medication, and number of comorbidities. Specifically, the results of these models showed that patients who had both high CRP and IL-6 at baseline had a threefold higher risk of experiencing a decline in frailty status.

So, in conclusion, this study shows a significant association between systemic inflammation and a decline in frailty status in elderly patients receiving chemotherapy for early-stage breast cancer. From a biological perspective, these higher levels of systemic inflammation might be a direct byproduct of a more advanced biological aging following the accumulation of senescent cells. There are several intriguing future perspectives that come from this study. First, if validated in additional cohorts, these findings might lead to higher treatment personalization thanks to the identification of patients at risk of clinical decline based on clinical characteristics but also on systemic inflammation. And these patients could be then proactively supported during chemotherapy to try and reduce the appearance of the clinical decline. Second, we know that inflammation is a potentially targetable pathway, and previous data obtained in breast cancer patients showed the potential of behavioral, exercise, and dietary interventions in modulating systemic inflammation. So, based on this new information, if validated in additional cohorts, future research should then evaluate if this interventions can be used to treat and eventually prevent the decline in frailty status in patients with high baseline systemic inflammation before receiving chemotherapy.

This is Davide Soldato in this episode of JCO Article Insights. We discussed two publications: ‘Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women: Results from the Prospective Multicenter HOPE Trial’, and the second one, ‘Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults with Breast cancer: Results from the Hurria Older Patients Prospective Study’.

Thank you for your attention, and stay tuned for the next episode.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Like, share and subscribe so you never miss an episode and leave a rating or review.

Articles

Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women

Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults With Breast Cancer

Find more articles from the January 10 issue.

  continue reading

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