AVAHO

SINGAPORE – Can the prolonged use of skin-lightening products, such as hydroquinone, lead to skin cancer?

This question was posed by Ousmane Faye, MD, PhD, director general of Mali’s Bamako Dermatology Hospital, at the World Congress of Dermatology. 

Dr. Faye explored the issue during a hot topics session at the meeting, prefacing that it was an important question to ask because “in West Africa, skin bleaching is very common.”

“There are many local names” for skin bleaching, he said. “For example, in Senegal, it’s called xessal; in Mali and Ivory Coast, its name is caco; in South Africa, there are many names, like ukutsheyisa.”

Skin bleaching refers to the cosmetic misuse of topical agents to change one’s natural skin color. It’s a centuries-old practice that people, mainly women, adopt “to increase attractiveness and self-esteem,” explained Dr. Faye.

To demonstrate how pervasive skin bleaching is on the continent, he presented a slide that summarized figures from six studies spanning the past 2 decades. Prevalence ranged from 25% in Mali (based on a 1993 survey of 210 women) to a high of 79.25% in Benin (from a sample size of 511 women in 2019). In other studies of women in Burkina Faso and Togo, the figures were 44.3% and 58.9%, respectively. The most recently conducted study, which involved 2,689 Senegalese women and was published in 2022, found that nearly 6 in 10 (59.2%) respondents used skin-lightening products.

But skin bleaching isn’t just limited to Africa, said session moderator Omar Lupi, MD, PhD, associate professor of dermatology at the Federal University of the State of Rio de Janeiro, when approached for an independent comment. “It’s a traditional practice around the world. Maybe not in the developed countries, but it’s quite common in Africa, in South America, and in Asia.”

His sentiments are echoed in a meta-analysis that was published in the International Journal of Dermatology in 2019. The work examined 68 studies involving more than 67,000 people across Africa, Asia, Europe, the Middle East, and North America. It found that the pooled lifetime prevalence of skin bleaching was 27.7% (95% confidence interval, 19.6-37.5; P < .01).

“This is an important and interesting topic because our world is shrinking,” Dr. Lupi told this news organization. “Even in countries that don’t have bleaching as a common situation, we now have patients who are migrating from one part [of the world] to another, so bleaching is something that can knock on your door and you need to be prepared.”

Misuse leads to complications

The issue is pertinent to dermatologists because skin bleaching is associated with a wide range of complications. Take, for example, topical steroids, which are the most common products used for bleaching, said Dr. Faye in his talk. 

“Clobetasol can suppress the hypothalamic-pituitary-adrenal (HPA) function,” he said, referring to the body’s main stress response system. “It can also foster skin infection, including bacterial, fungal, viral, and parasitic infection.”

In addition, topical steroids that are misused as skin lighteners have been reported to cause stretch marks, skin atrophy, inflammatory acne, and even metabolic disorders such as diabetes and hypertension, said Dr. Faye.

To further his point, he cited a 2021 prospective case-control study conducted across five sub-Saharan countries, which found that the use of “voluntary cosmetic depigmentation” significantly increased a person’s risk for necrotizing fasciitis of the lower limbs (odds ratio, 2.29; 95% CI, 1.19-3.73; P = .0226).

Similarly, mercury, another substance found in products commonly used to bleach skin, has been associated with problems ranging from rashes to renal toxicity. And because it’s so incredibly harmful, mercury is also known to cause neurologic abnormalities. 

Apart from causing certain conditions, prolonged use of skin-lightening products can change the way existing diseases present themselves as well as their severity, added Dr. Faye. 
 

An increased risk

But what about skin bleaching’s link with cancer? “Skin cancer on Black skin is uncommon, yet it occurs in skin-bleaching women,” said Dr. Faye.

“Since 2000, we have had some cases of skin cancer associated with skin bleaching,” he continued, adding that squamous cell carcinoma (SCC) is the most frequent type of cancer observed. 

If you look at what’s been published on the topic so far, you’ll see that “all the cases of skin cancer are located over the neck or some exposed area when skin bleaching products are used for more than 10 years,” said Dr. Faye. “And most of the time, the age of the patient ranges from 30 to 60 years.”

The first known case in Africa was reported in a 58-year-old woman from Ghana, who had been using skin bleaching products for close to 30 years. The patient presented with tumors on her face, neck, and arms.

Dr. Faye then proceeded to share more than 10 such carcinoma cases. “These previous reports strongly suggest a relationship between skin bleaching and skin cancers,” said Dr. Faye.

Indeed, there have been reports and publications in the literature that support his observation, including one last year, which found that use of the tyrosinase inhibitor hydroquinone was associated with approximately a threefold increased risk for skin cancer.

For some, including Brazil’s Dr. Lupi, Dr. Faye’s talk was enlightening: “I didn’t know about this relationship [of bleaching] with skin cancer, it was something new for me.”

But the prevalence of SCC is very low, compared with that of skin bleaching, Dr. Faye acknowledged. Moreover, the cancer observed in the cases reported could have resulted from a number of reasons, including exposure to harmful ultraviolet rays from the sun and genetic predisposition in addition to the use of bleaching products such as hydroquinone. “Other causes of skin cancer are not excluded,” he said.

To further explore the link between skin bleaching and cancer, “we need case-control studies to provide more evidence,” he added. Until then, dermatologists “should keep on promoting messages” to prevent SCC from occurring. This includes encouraging the use of proper sun protection in addition to discouraging the practice of skin bleaching, which still persists despite more than 10 African nations banning the use of toxic skin-lightening products.

Dr. Faye and Dr. Lupi report no relevant financial relationships.

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

SINGAPORE – Can the prolonged use of skin-lightening products, such as hydroquinone, lead to skin cancer?

This question was posed by Ousmane Faye, MD, PhD, director general of Mali’s Bamako Dermatology Hospital, at the World Congress of Dermatology. 

Dr. Faye explored the issue during a hot topics session at the meeting, prefacing that it was an important question to ask because “in West Africa, skin bleaching is very common.”

“There are many local names” for skin bleaching, he said. “For example, in Senegal, it’s called xessal; in Mali and Ivory Coast, its name is caco; in South Africa, there are many names, like ukutsheyisa.”

Skin bleaching refers to the cosmetic misuse of topical agents to change one’s natural skin color. It’s a centuries-old practice that people, mainly women, adopt “to increase attractiveness and self-esteem,” explained Dr. Faye.

To demonstrate how pervasive skin bleaching is on the continent, he presented a slide that summarized figures from six studies spanning the past 2 decades. Prevalence ranged from 25% in Mali (based on a 1993 survey of 210 women) to a high of 79.25% in Benin (from a sample size of 511 women in 2019). In other studies of women in Burkina Faso and Togo, the figures were 44.3% and 58.9%, respectively. The most recently conducted study, which involved 2,689 Senegalese women and was published in 2022, found that nearly 6 in 10 (59.2%) respondents used skin-lightening products.

But skin bleaching isn’t just limited to Africa, said session moderator Omar Lupi, MD, PhD, associate professor of dermatology at the Federal University of the State of Rio de Janeiro, when approached for an independent comment. “It’s a traditional practice around the world. Maybe not in the developed countries, but it’s quite common in Africa, in South America, and in Asia.”

His sentiments are echoed in a meta-analysis that was published in the International Journal of Dermatology in 2019. The work examined 68 studies involving more than 67,000 people across Africa, Asia, Europe, the Middle East, and North America. It found that the pooled lifetime prevalence of skin bleaching was 27.7% (95% confidence interval, 19.6-37.5; P < .01).

“This is an important and interesting topic because our world is shrinking,” Dr. Lupi told this news organization. “Even in countries that don’t have bleaching as a common situation, we now have patients who are migrating from one part [of the world] to another, so bleaching is something that can knock on your door and you need to be prepared.”

Misuse leads to complications

The issue is pertinent to dermatologists because skin bleaching is associated with a wide range of complications. Take, for example, topical steroids, which are the most common products used for bleaching, said Dr. Faye in his talk. 

“Clobetasol can suppress the hypothalamic-pituitary-adrenal (HPA) function,” he said, referring to the body’s main stress response system. “It can also foster skin infection, including bacterial, fungal, viral, and parasitic infection.”

In addition, topical steroids that are misused as skin lighteners have been reported to cause stretch marks, skin atrophy, inflammatory acne, and even metabolic disorders such as diabetes and hypertension, said Dr. Faye.

To further his point, he cited a 2021 prospective case-control study conducted across five sub-Saharan countries, which found that the use of “voluntary cosmetic depigmentation” significantly increased a person’s risk for necrotizing fasciitis of the lower limbs (odds ratio, 2.29; 95% CI, 1.19-3.73; P = .0226).

Similarly, mercury, another substance found in products commonly used to bleach skin, has been associated with problems ranging from rashes to renal toxicity. And because it’s so incredibly harmful, mercury is also known to cause neurologic abnormalities. 

Apart from causing certain conditions, prolonged use of skin-lightening products can change the way existing diseases present themselves as well as their severity, added Dr. Faye. 
 

An increased risk

But what about skin bleaching’s link with cancer? “Skin cancer on Black skin is uncommon, yet it occurs in skin-bleaching women,” said Dr. Faye.

“Since 2000, we have had some cases of skin cancer associated with skin bleaching,” he continued, adding that squamous cell carcinoma (SCC) is the most frequent type of cancer observed. 

If you look at what’s been published on the topic so far, you’ll see that “all the cases of skin cancer are located over the neck or some exposed area when skin bleaching products are used for more than 10 years,” said Dr. Faye. “And most of the time, the age of the patient ranges from 30 to 60 years.”

The first known case in Africa was reported in a 58-year-old woman from Ghana, who had been using skin bleaching products for close to 30 years. The patient presented with tumors on her face, neck, and arms.

Dr. Faye then proceeded to share more than 10 such carcinoma cases. “These previous reports strongly suggest a relationship between skin bleaching and skin cancers,” said Dr. Faye.

Indeed, there have been reports and publications in the literature that support his observation, including one last year, which found that use of the tyrosinase inhibitor hydroquinone was associated with approximately a threefold increased risk for skin cancer.

For some, including Brazil’s Dr. Lupi, Dr. Faye’s talk was enlightening: “I didn’t know about this relationship [of bleaching] with skin cancer, it was something new for me.”

But the prevalence of SCC is very low, compared with that of skin bleaching, Dr. Faye acknowledged. Moreover, the cancer observed in the cases reported could have resulted from a number of reasons, including exposure to harmful ultraviolet rays from the sun and genetic predisposition in addition to the use of bleaching products such as hydroquinone. “Other causes of skin cancer are not excluded,” he said.

To further explore the link between skin bleaching and cancer, “we need case-control studies to provide more evidence,” he added. Until then, dermatologists “should keep on promoting messages” to prevent SCC from occurring. This includes encouraging the use of proper sun protection in addition to discouraging the practice of skin bleaching, which still persists despite more than 10 African nations banning the use of toxic skin-lightening products.

Dr. Faye and Dr. Lupi report no relevant financial relationships.

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

SINGAPORE – Can the prolonged use of skin-lightening products, such as hydroquinone, lead to skin cancer?

This question was posed by Ousmane Faye, MD, PhD, director general of Mali’s Bamako Dermatology Hospital, at the World Congress of Dermatology. 

Dr. Faye explored the issue during a hot topics session at the meeting, prefacing that it was an important question to ask because “in West Africa, skin bleaching is very common.”

“There are many local names” for skin bleaching, he said. “For example, in Senegal, it’s called xessal; in Mali and Ivory Coast, its name is caco; in South Africa, there are many names, like ukutsheyisa.”

Skin bleaching refers to the cosmetic misuse of topical agents to change one’s natural skin color. It’s a centuries-old practice that people, mainly women, adopt “to increase attractiveness and self-esteem,” explained Dr. Faye.

To demonstrate how pervasive skin bleaching is on the continent, he presented a slide that summarized figures from six studies spanning the past 2 decades. Prevalence ranged from 25% in Mali (based on a 1993 survey of 210 women) to a high of 79.25% in Benin (from a sample size of 511 women in 2019). In other studies of women in Burkina Faso and Togo, the figures were 44.3% and 58.9%, respectively. The most recently conducted study, which involved 2,689 Senegalese women and was published in 2022, found that nearly 6 in 10 (59.2%) respondents used skin-lightening products.

But skin bleaching isn’t just limited to Africa, said session moderator Omar Lupi, MD, PhD, associate professor of dermatology at the Federal University of the State of Rio de Janeiro, when approached for an independent comment. “It’s a traditional practice around the world. Maybe not in the developed countries, but it’s quite common in Africa, in South America, and in Asia.”

His sentiments are echoed in a meta-analysis that was published in the International Journal of Dermatology in 2019. The work examined 68 studies involving more than 67,000 people across Africa, Asia, Europe, the Middle East, and North America. It found that the pooled lifetime prevalence of skin bleaching was 27.7% (95% confidence interval, 19.6-37.5; P < .01).

“This is an important and interesting topic because our world is shrinking,” Dr. Lupi told this news organization. “Even in countries that don’t have bleaching as a common situation, we now have patients who are migrating from one part [of the world] to another, so bleaching is something that can knock on your door and you need to be prepared.”

Misuse leads to complications

The issue is pertinent to dermatologists because skin bleaching is associated with a wide range of complications. Take, for example, topical steroids, which are the most common products used for bleaching, said Dr. Faye in his talk. 

“Clobetasol can suppress the hypothalamic-pituitary-adrenal (HPA) function,” he said, referring to the body’s main stress response system. “It can also foster skin infection, including bacterial, fungal, viral, and parasitic infection.”

In addition, topical steroids that are misused as skin lighteners have been reported to cause stretch marks, skin atrophy, inflammatory acne, and even metabolic disorders such as diabetes and hypertension, said Dr. Faye.

To further his point, he cited a 2021 prospective case-control study conducted across five sub-Saharan countries, which found that the use of “voluntary cosmetic depigmentation” significantly increased a person’s risk for necrotizing fasciitis of the lower limbs (odds ratio, 2.29; 95% CI, 1.19-3.73; P = .0226).

Similarly, mercury, another substance found in products commonly used to bleach skin, has been associated with problems ranging from rashes to renal toxicity. And because it’s so incredibly harmful, mercury is also known to cause neurologic abnormalities. 

Apart from causing certain conditions, prolonged use of skin-lightening products can change the way existing diseases present themselves as well as their severity, added Dr. Faye. 
 

An increased risk

But what about skin bleaching’s link with cancer? “Skin cancer on Black skin is uncommon, yet it occurs in skin-bleaching women,” said Dr. Faye.

“Since 2000, we have had some cases of skin cancer associated with skin bleaching,” he continued, adding that squamous cell carcinoma (SCC) is the most frequent type of cancer observed. 

If you look at what’s been published on the topic so far, you’ll see that “all the cases of skin cancer are located over the neck or some exposed area when skin bleaching products are used for more than 10 years,” said Dr. Faye. “And most of the time, the age of the patient ranges from 30 to 60 years.”

The first known case in Africa was reported in a 58-year-old woman from Ghana, who had been using skin bleaching products for close to 30 years. The patient presented with tumors on her face, neck, and arms.

Dr. Faye then proceeded to share more than 10 such carcinoma cases. “These previous reports strongly suggest a relationship between skin bleaching and skin cancers,” said Dr. Faye.

Indeed, there have been reports and publications in the literature that support his observation, including one last year, which found that use of the tyrosinase inhibitor hydroquinone was associated with approximately a threefold increased risk for skin cancer.

For some, including Brazil’s Dr. Lupi, Dr. Faye’s talk was enlightening: “I didn’t know about this relationship [of bleaching] with skin cancer, it was something new for me.”

But the prevalence of SCC is very low, compared with that of skin bleaching, Dr. Faye acknowledged. Moreover, the cancer observed in the cases reported could have resulted from a number of reasons, including exposure to harmful ultraviolet rays from the sun and genetic predisposition in addition to the use of bleaching products such as hydroquinone. “Other causes of skin cancer are not excluded,” he said.

To further explore the link between skin bleaching and cancer, “we need case-control studies to provide more evidence,” he added. Until then, dermatologists “should keep on promoting messages” to prevent SCC from occurring. This includes encouraging the use of proper sun protection in addition to discouraging the practice of skin bleaching, which still persists despite more than 10 African nations banning the use of toxic skin-lightening products.

Dr. Faye and Dr. Lupi report no relevant financial relationships.

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

Pleural mesothelioma is generally treated by extended pleurectomy decortication, and there has been little improvement in systemic treatment of early-stage, resectable mesothelioma, which has led to the recommendations of maximum cytoreduction. U.S. and European guidelines, as well as an international consensus statement, support this approach, but it has never been tested in a randomized, controlled trial.

Now it has, and the result is surprising: Surgery led to reduced survival and more serious adverse events, compared with chemotherapy alone. The conclusion was uncomfortable for Eric Lim, MD, who presented the results of the MARS2 trial at the annual World Conference on Lung Cancer. “Ladies and gentlemen, as a surgeon standing here, you have no idea how much it pains me to conclude that extended pleurectomy decortication, an operation that we have been offering for over 70 years, has been associated with a higher risk of death, more serious complications, poorer quality of life, and higher costs, compared to mesothelioma patients who were randomized to chemotherapy alone,” said Dr. Lim of the Royal Brompton Hospital, London, during his presentation.

Although the line drew laughter and applause from the audience, Paula Ugalde Figueroa, MD, who served as a discussant, raised some concerns about the study. Disease presence in one hemithorax was assessed only by chest CT scan, which is notorious for underestimating the volume of disease during surgery. There was also no information on pleural effusion or how many patients received it prior to intervention. Existing guidelines suggest staging of mesothelioma should also use PET scans, and invasive mediastinal staging should be assessed with endobronchial ultrasound. “None of these were performed during the trial,” said Dr. Figueroa, who is an associate thoracic surgeon at Brigham and Women’s Hospital, Boston. “At this point, my question is, are the arms of this study well balanced in regard to tumor volume? We don’t know,” she added.

Dr. Figueroa noted that the 90-day mortality seemed higher than that seen in other studies. “So, does the surgeon’s experience and center volume affect the outcome of this study?” she asked. Dr. Figueroa personally made phone calls to the participating centers and found that 45% of the patients in the trial were treated at low-volume centers, defined by her as two to three patients per year. “Should we assume that their surgical outcomes are similar between those centers? In this trial, with approximately half of patients from low-volume centers, extended pleurectomy decortication for mesothelioma had no significant difference when compared to those patients that underwent chemotherapy alone. Would the outcome be different in exclusively high-volume centers?” she concluded.

The study randomized 335 patients to receive surgery and chemotherapy, or chemotherapy alone. They received two cycles of platinum-based chemotherapy and pemetrexed prior to surgery and up to four cycles after surgery. The average age was 69 years; 86.9% were male, and 85.7% of tumors were epithelioid only. Among those in the surgery group, 88.5% underwent extended pleurectomy/decortication, 8.3% underwent pleurectomy decortication, 1.9% underwent partial pleurectomy, 0.6% exploration with no pleurodesis, and 0.6% were classified as “other” surgery. Completeness of resection was R0 in 3.2% of surgeries, R1 in 80.9%, and R2 in 15.9%. In-hospital mortality occurred in 3.8% of patients, and postsurgical 90-day mortality was 8.9%.

Over the first 42 months of follow-up, the hazard ratio for overall survival was 1.28 in the no-surgery group (P = .03). “The survival was so good in this early-stage cohort that we had to extend the trial by 6 months to get the prerequisite number of deaths, underscoring the phenomenal importance of having a randomized comparative cohort for all future studies on surgery for mesothelioma,” said Dr. Lim.

After 42 months, there was no survival difference between the two groups (hazard ratio, 0.48; P = .15). Dr. Lim attributed the change at 42 months to the fact that only 15 patients remained in each arm at that stage. There was no significant difference between the two groups with respect to progression-free survival.

The survival benefit of the no-surgery group was sustained after additional analyses, including adjustment of the number of first-line chemotherapy cycles and immunotherapy received after completion of the trial protocol.

Adverse events were more common in the surgery group (incidence rate ratio, 3.6; P < .001), including any cardiac disorder (IRR, 2.73; 95% confidence interval, 1.11-6.67); any infection or infestation (IRR, 1.99; 95% CI, 1.33-2.99); any respiratory, thoracic, or mediastinal disorder (IRR, 2.40; 95% CI, 1.52-3.80); and any surgical or medical procedure (IRR, 2.23; 95% CI, 1.04-4.78). The EORTC quality of life score favored the nonsurgery group at 6 weeks, but there was no significant difference at other time points.

Dr. Lim and Dr. Figueroa have no relevant financial disclosures.

Pleural mesothelioma is generally treated by extended pleurectomy decortication, and there has been little improvement in systemic treatment of early-stage, resectable mesothelioma, which has led to the recommendations of maximum cytoreduction. U.S. and European guidelines, as well as an international consensus statement, support this approach, but it has never been tested in a randomized, controlled trial.

Now it has, and the result is surprising: Surgery led to reduced survival and more serious adverse events, compared with chemotherapy alone. The conclusion was uncomfortable for Eric Lim, MD, who presented the results of the MARS2 trial at the annual World Conference on Lung Cancer. “Ladies and gentlemen, as a surgeon standing here, you have no idea how much it pains me to conclude that extended pleurectomy decortication, an operation that we have been offering for over 70 years, has been associated with a higher risk of death, more serious complications, poorer quality of life, and higher costs, compared to mesothelioma patients who were randomized to chemotherapy alone,” said Dr. Lim of the Royal Brompton Hospital, London, during his presentation.

Although the line drew laughter and applause from the audience, Paula Ugalde Figueroa, MD, who served as a discussant, raised some concerns about the study. Disease presence in one hemithorax was assessed only by chest CT scan, which is notorious for underestimating the volume of disease during surgery. There was also no information on pleural effusion or how many patients received it prior to intervention. Existing guidelines suggest staging of mesothelioma should also use PET scans, and invasive mediastinal staging should be assessed with endobronchial ultrasound. “None of these were performed during the trial,” said Dr. Figueroa, who is an associate thoracic surgeon at Brigham and Women’s Hospital, Boston. “At this point, my question is, are the arms of this study well balanced in regard to tumor volume? We don’t know,” she added.

Dr. Figueroa noted that the 90-day mortality seemed higher than that seen in other studies. “So, does the surgeon’s experience and center volume affect the outcome of this study?” she asked. Dr. Figueroa personally made phone calls to the participating centers and found that 45% of the patients in the trial were treated at low-volume centers, defined by her as two to three patients per year. “Should we assume that their surgical outcomes are similar between those centers? In this trial, with approximately half of patients from low-volume centers, extended pleurectomy decortication for mesothelioma had no significant difference when compared to those patients that underwent chemotherapy alone. Would the outcome be different in exclusively high-volume centers?” she concluded.

The study randomized 335 patients to receive surgery and chemotherapy, or chemotherapy alone. They received two cycles of platinum-based chemotherapy and pemetrexed prior to surgery and up to four cycles after surgery. The average age was 69 years; 86.9% were male, and 85.7% of tumors were epithelioid only. Among those in the surgery group, 88.5% underwent extended pleurectomy/decortication, 8.3% underwent pleurectomy decortication, 1.9% underwent partial pleurectomy, 0.6% exploration with no pleurodesis, and 0.6% were classified as “other” surgery. Completeness of resection was R0 in 3.2% of surgeries, R1 in 80.9%, and R2 in 15.9%. In-hospital mortality occurred in 3.8% of patients, and postsurgical 90-day mortality was 8.9%.

Over the first 42 months of follow-up, the hazard ratio for overall survival was 1.28 in the no-surgery group (P = .03). “The survival was so good in this early-stage cohort that we had to extend the trial by 6 months to get the prerequisite number of deaths, underscoring the phenomenal importance of having a randomized comparative cohort for all future studies on surgery for mesothelioma,” said Dr. Lim.

After 42 months, there was no survival difference between the two groups (hazard ratio, 0.48; P = .15). Dr. Lim attributed the change at 42 months to the fact that only 15 patients remained in each arm at that stage. There was no significant difference between the two groups with respect to progression-free survival.

The survival benefit of the no-surgery group was sustained after additional analyses, including adjustment of the number of first-line chemotherapy cycles and immunotherapy received after completion of the trial protocol.

Adverse events were more common in the surgery group (incidence rate ratio, 3.6; P < .001), including any cardiac disorder (IRR, 2.73; 95% confidence interval, 1.11-6.67); any infection or infestation (IRR, 1.99; 95% CI, 1.33-2.99); any respiratory, thoracic, or mediastinal disorder (IRR, 2.40; 95% CI, 1.52-3.80); and any surgical or medical procedure (IRR, 2.23; 95% CI, 1.04-4.78). The EORTC quality of life score favored the nonsurgery group at 6 weeks, but there was no significant difference at other time points.

Dr. Lim and Dr. Figueroa have no relevant financial disclosures.

Pleural mesothelioma is generally treated by extended pleurectomy decortication, and there has been little improvement in systemic treatment of early-stage, resectable mesothelioma, which has led to the recommendations of maximum cytoreduction. U.S. and European guidelines, as well as an international consensus statement, support this approach, but it has never been tested in a randomized, controlled trial.

Now it has, and the result is surprising: Surgery led to reduced survival and more serious adverse events, compared with chemotherapy alone. The conclusion was uncomfortable for Eric Lim, MD, who presented the results of the MARS2 trial at the annual World Conference on Lung Cancer. “Ladies and gentlemen, as a surgeon standing here, you have no idea how much it pains me to conclude that extended pleurectomy decortication, an operation that we have been offering for over 70 years, has been associated with a higher risk of death, more serious complications, poorer quality of life, and higher costs, compared to mesothelioma patients who were randomized to chemotherapy alone,” said Dr. Lim of the Royal Brompton Hospital, London, during his presentation.

Although the line drew laughter and applause from the audience, Paula Ugalde Figueroa, MD, who served as a discussant, raised some concerns about the study. Disease presence in one hemithorax was assessed only by chest CT scan, which is notorious for underestimating the volume of disease during surgery. There was also no information on pleural effusion or how many patients received it prior to intervention. Existing guidelines suggest staging of mesothelioma should also use PET scans, and invasive mediastinal staging should be assessed with endobronchial ultrasound. “None of these were performed during the trial,” said Dr. Figueroa, who is an associate thoracic surgeon at Brigham and Women’s Hospital, Boston. “At this point, my question is, are the arms of this study well balanced in regard to tumor volume? We don’t know,” she added.

Dr. Figueroa noted that the 90-day mortality seemed higher than that seen in other studies. “So, does the surgeon’s experience and center volume affect the outcome of this study?” she asked. Dr. Figueroa personally made phone calls to the participating centers and found that 45% of the patients in the trial were treated at low-volume centers, defined by her as two to three patients per year. “Should we assume that their surgical outcomes are similar between those centers? In this trial, with approximately half of patients from low-volume centers, extended pleurectomy decortication for mesothelioma had no significant difference when compared to those patients that underwent chemotherapy alone. Would the outcome be different in exclusively high-volume centers?” she concluded.

The study randomized 335 patients to receive surgery and chemotherapy, or chemotherapy alone. They received two cycles of platinum-based chemotherapy and pemetrexed prior to surgery and up to four cycles after surgery. The average age was 69 years; 86.9% were male, and 85.7% of tumors were epithelioid only. Among those in the surgery group, 88.5% underwent extended pleurectomy/decortication, 8.3% underwent pleurectomy decortication, 1.9% underwent partial pleurectomy, 0.6% exploration with no pleurodesis, and 0.6% were classified as “other” surgery. Completeness of resection was R0 in 3.2% of surgeries, R1 in 80.9%, and R2 in 15.9%. In-hospital mortality occurred in 3.8% of patients, and postsurgical 90-day mortality was 8.9%.

Over the first 42 months of follow-up, the hazard ratio for overall survival was 1.28 in the no-surgery group (P = .03). “The survival was so good in this early-stage cohort that we had to extend the trial by 6 months to get the prerequisite number of deaths, underscoring the phenomenal importance of having a randomized comparative cohort for all future studies on surgery for mesothelioma,” said Dr. Lim.

After 42 months, there was no survival difference between the two groups (hazard ratio, 0.48; P = .15). Dr. Lim attributed the change at 42 months to the fact that only 15 patients remained in each arm at that stage. There was no significant difference between the two groups with respect to progression-free survival.

The survival benefit of the no-surgery group was sustained after additional analyses, including adjustment of the number of first-line chemotherapy cycles and immunotherapy received after completion of the trial protocol.

Adverse events were more common in the surgery group (incidence rate ratio, 3.6; P < .001), including any cardiac disorder (IRR, 2.73; 95% confidence interval, 1.11-6.67); any infection or infestation (IRR, 1.99; 95% CI, 1.33-2.99); any respiratory, thoracic, or mediastinal disorder (IRR, 2.40; 95% CI, 1.52-3.80); and any surgical or medical procedure (IRR, 2.23; 95% CI, 1.04-4.78). The EORTC quality of life score favored the nonsurgery group at 6 weeks, but there was no significant difference at other time points.

Dr. Lim and Dr. Figueroa have no relevant financial disclosures.

What happens to grief when those around you don’t understand it? Where does it go? How do you process it?

Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.

Here, we reflect as physicians on our own experiences and memories of this phenomenon.
 

Suzanne Cole, MD: ‘I didn’t feel the right to grieve’

During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.

Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.

But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.

To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
 

Don S. Dizon, MD: Working through tragedy

As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.

But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.

Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.

By the time help arrived, the patient was blue.

He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.

As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
 

A space for grieving: The Schwartz Center Rounds

Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.

Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.

More and more, though, we are being given opportunities to reflect on these sad moments.

The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.

During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.

As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.

Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.

Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.

As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.

We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.

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

What happens to grief when those around you don’t understand it? Where does it go? How do you process it?

Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.

Here, we reflect as physicians on our own experiences and memories of this phenomenon.
 

Suzanne Cole, MD: ‘I didn’t feel the right to grieve’

During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.

Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.

But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.

To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
 

Don S. Dizon, MD: Working through tragedy

As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.

But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.

Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.

By the time help arrived, the patient was blue.

He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.

As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
 

A space for grieving: The Schwartz Center Rounds

Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.

Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.

More and more, though, we are being given opportunities to reflect on these sad moments.

The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.

During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.

As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.

Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.

Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.

As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.

We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.

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

What happens to grief when those around you don’t understand it? Where does it go? How do you process it?

Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.

Here, we reflect as physicians on our own experiences and memories of this phenomenon.
 

Suzanne Cole, MD: ‘I didn’t feel the right to grieve’

During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.

Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.

But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.

To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
 

Don S. Dizon, MD: Working through tragedy

As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.

But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.

Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.

By the time help arrived, the patient was blue.

He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.

As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
 

A space for grieving: The Schwartz Center Rounds

Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.

Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.

More and more, though, we are being given opportunities to reflect on these sad moments.

The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.

During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.

As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.

Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.

Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.

As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.

We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.

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

Antibody-drug conjugates (ADC) link a tumor-targeted antibody to a cytotoxic drug through a chemical linker and hold the promise of high potency. This has led to a burgeoning interest in solid tumors, with over 100 clinical trials in progress. Non–small cell lung cancer (NSCLC) is no exception. In 2022, the Food and Drug Administration approved trastuzumab DXd for pretreated NSCLC patients with HER2-mutant tumors. Two others have lung cancer breakthrough therapy designations from the FDA, including patritumab deruxtecan (HER3-DXd) for EGFR-mutant NSCLC and telisotuzumab vedotin for NSCLC that overexpresses c-Met.

At the annual World Conference on Lung Cancer, researchers outlined some of the latest developments in ADCs targeting the antigens HER3, trophoblast cell-surface antigen 2 (TROP-2), and the B7-H3 immunoregulatory protein, as single agents or in combination with immunotherapy. Following the presentations, discussant Helena Linardou, MD, PhD, emphasized the need for pharmacogenomics to predict toxicity and studies to understand resistance mechanisms. “ADCs are a new, rapidly evolving class of therapeutics, and I think that we will all have to be prepared for the future that is coming,” said Dr. Linardou, who is director of the 4th oncology department and the Comprehensive Clinical Trials Center at Metropolitan Hospital in Athens.

Researchers presented four ADC clinical trial updates.
 

Patritumab deruxtecan

Patritumab deruxtecan (Daiichi Sankyo) links a HER3 antibody to the topoisomerase I inhibitor deruxtecan (HER3-DXd). In the open-label, phase 2 HERTHENA-Lung01 trial, it was tested in patients with NSCLC EGFR-activation mutations, which occurs in 14%-38% of NSCLC cases. There are few options for these patients following failure of EGFR tyrosine kinase inhibitor therapy.

The study included 225 patients previously treated with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy who received 5.6 mg/kg of HER3-DXd every 3 weeks. Over a median follow-up of 13.1 months and a median treatment duration of 5.5 months), 29.8% had a confirmed overall response (95% confidence interval, 23.9%-36.2%) with a median duration of 6.4 months (95% CI, 4.9-7.8). The median progression-free survival was 5.5 months (95% CI, 5.1-5.9), and the median OS was 11.9 months (95% CI, 11.2-13.1). The researchers noted similar outcomes among patients with different mechanisms of EGFR TKI resistance. The frequency of adverse events was similar to previous studies, with drug-related adverse events linked to treatment discontinuation of 7.1% interstitial lung disease in 5.3%. Among 30 patients with brain metastases, the confirmed intracranial response rate was 33.3% (95% CI, 17.3%-52.8%).

The study was published simultaneously online in the Journal of Clinical Oncology. (Abstract)
 

Datopotamab deruxtecan

PD-1/PD-L1 inhibitors are the first-line therapy for metastatic NSCLC, but there are efforts to improve outcomes through combination therapy. Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo, AstraZeneca) is an ADC targeting TROP2, and it has been shown in preclinical studies to enhance tumor responses to PD-1/PD-L1 inhibitors. The ADC improved progression-free survival (PFS), compared with docetaxel, in previously treated advanced or metastatic NSCLC.

In an interim analysis of the phase 1b TROPION-Lung04 study, researchers reported results from the combination of Dato-DXd with durvalumab with or without carboplatin. The study included 38 patients, some of whom had previously undergone treatment with immune checkpoint inhibitors. Nineteen patients received the doublet, and 14 received the carboplatin triplet. Grade 3 or higher treatment-emergent adverse events occurred in 42.1% of the doublet group and 71.4% of the triplet group. Interstitial lung disease occurred in 15.8% and 7.1% of the two groups, respectively. The objective response rate was 50.0% in the doublet group and 76.9% in the triplet group. The disease control rate was 92.9% and 92.3%, respectively. Durable responses occurred in both the first-line setting and the overall population. (Abstract)
 

Sacituzumab govitecan

Another ADC being tested with PD-1/PD-L1 inhibitors is sacituzumab govitecan (Trodelvy, Gilead), which has already received FDA approval for metastatic triple-negative breast cancer, pretreated HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer. Like datopotamab, sacituzumab targets TROP-2. Researchers reported preliminary results from the phase 2 EVOKE-02 study, in which the ADC was combined with pembrolizumab for the first-line treatment of metastatic NSCLC. The overall response rate was 56% (95% CI, 42%-69%). Among patients with PD-L1 tumor proportion score (TPS) ≥ 50%, the ORR was 69% (95% CI, 49%-85%) and 44% (95% CI, 26%-62%) among those with TPS < 50%. The disease control rate was 86% (95% CI, 68%-96%) and 78% (95% CI, 60%-91%), respectively. The most frequent treatment-emergent adverse events (TEAEs) were diarrhea, anemia, and asthenia, and 18% of patients discontinued the study drug because of TEAEs. (Abstract)

Ifinatamab deruxtecan

Ifinatamab deruxtecan (Daiichi Sankyo) targets the B7-H3 antigen, which is an immunoregulatory protein that is overexpressed in many tumors. In the DS7300-A-J101 study, it was tested in patients with advanced or metastatic solid tumors, without selection for B7-H3 expression. A subgroup analysis of 22 patients with small cell lung cancer (SCLC) showed an ORR of 52.4 (95% CI, 29.8-74.3), a complete response of 4.8%, and a partial response in 47.6%. The median PFS was 5.6 months (95% CI, 3.9-8.1) and median OS was 12.2 months (95% CI, 6.4-not applicable). The most common treatment-emergent adverse events were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%), and decreased appetite (22.7%). (Abstract)

Antibody-drug conjugates (ADC) link a tumor-targeted antibody to a cytotoxic drug through a chemical linker and hold the promise of high potency. This has led to a burgeoning interest in solid tumors, with over 100 clinical trials in progress. Non–small cell lung cancer (NSCLC) is no exception. In 2022, the Food and Drug Administration approved trastuzumab DXd for pretreated NSCLC patients with HER2-mutant tumors. Two others have lung cancer breakthrough therapy designations from the FDA, including patritumab deruxtecan (HER3-DXd) for EGFR-mutant NSCLC and telisotuzumab vedotin for NSCLC that overexpresses c-Met.

At the annual World Conference on Lung Cancer, researchers outlined some of the latest developments in ADCs targeting the antigens HER3, trophoblast cell-surface antigen 2 (TROP-2), and the B7-H3 immunoregulatory protein, as single agents or in combination with immunotherapy. Following the presentations, discussant Helena Linardou, MD, PhD, emphasized the need for pharmacogenomics to predict toxicity and studies to understand resistance mechanisms. “ADCs are a new, rapidly evolving class of therapeutics, and I think that we will all have to be prepared for the future that is coming,” said Dr. Linardou, who is director of the 4th oncology department and the Comprehensive Clinical Trials Center at Metropolitan Hospital in Athens.

Researchers presented four ADC clinical trial updates.
 

Patritumab deruxtecan

Patritumab deruxtecan (Daiichi Sankyo) links a HER3 antibody to the topoisomerase I inhibitor deruxtecan (HER3-DXd). In the open-label, phase 2 HERTHENA-Lung01 trial, it was tested in patients with NSCLC EGFR-activation mutations, which occurs in 14%-38% of NSCLC cases. There are few options for these patients following failure of EGFR tyrosine kinase inhibitor therapy.

The study included 225 patients previously treated with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy who received 5.6 mg/kg of HER3-DXd every 3 weeks. Over a median follow-up of 13.1 months and a median treatment duration of 5.5 months), 29.8% had a confirmed overall response (95% confidence interval, 23.9%-36.2%) with a median duration of 6.4 months (95% CI, 4.9-7.8). The median progression-free survival was 5.5 months (95% CI, 5.1-5.9), and the median OS was 11.9 months (95% CI, 11.2-13.1). The researchers noted similar outcomes among patients with different mechanisms of EGFR TKI resistance. The frequency of adverse events was similar to previous studies, with drug-related adverse events linked to treatment discontinuation of 7.1% interstitial lung disease in 5.3%. Among 30 patients with brain metastases, the confirmed intracranial response rate was 33.3% (95% CI, 17.3%-52.8%).

The study was published simultaneously online in the Journal of Clinical Oncology. (Abstract)
 

Datopotamab deruxtecan

PD-1/PD-L1 inhibitors are the first-line therapy for metastatic NSCLC, but there are efforts to improve outcomes through combination therapy. Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo, AstraZeneca) is an ADC targeting TROP2, and it has been shown in preclinical studies to enhance tumor responses to PD-1/PD-L1 inhibitors. The ADC improved progression-free survival (PFS), compared with docetaxel, in previously treated advanced or metastatic NSCLC.

In an interim analysis of the phase 1b TROPION-Lung04 study, researchers reported results from the combination of Dato-DXd with durvalumab with or without carboplatin. The study included 38 patients, some of whom had previously undergone treatment with immune checkpoint inhibitors. Nineteen patients received the doublet, and 14 received the carboplatin triplet. Grade 3 or higher treatment-emergent adverse events occurred in 42.1% of the doublet group and 71.4% of the triplet group. Interstitial lung disease occurred in 15.8% and 7.1% of the two groups, respectively. The objective response rate was 50.0% in the doublet group and 76.9% in the triplet group. The disease control rate was 92.9% and 92.3%, respectively. Durable responses occurred in both the first-line setting and the overall population. (Abstract)
 

Sacituzumab govitecan

Another ADC being tested with PD-1/PD-L1 inhibitors is sacituzumab govitecan (Trodelvy, Gilead), which has already received FDA approval for metastatic triple-negative breast cancer, pretreated HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer. Like datopotamab, sacituzumab targets TROP-2. Researchers reported preliminary results from the phase 2 EVOKE-02 study, in which the ADC was combined with pembrolizumab for the first-line treatment of metastatic NSCLC. The overall response rate was 56% (95% CI, 42%-69%). Among patients with PD-L1 tumor proportion score (TPS) ≥ 50%, the ORR was 69% (95% CI, 49%-85%) and 44% (95% CI, 26%-62%) among those with TPS < 50%. The disease control rate was 86% (95% CI, 68%-96%) and 78% (95% CI, 60%-91%), respectively. The most frequent treatment-emergent adverse events (TEAEs) were diarrhea, anemia, and asthenia, and 18% of patients discontinued the study drug because of TEAEs. (Abstract)

Ifinatamab deruxtecan

Ifinatamab deruxtecan (Daiichi Sankyo) targets the B7-H3 antigen, which is an immunoregulatory protein that is overexpressed in many tumors. In the DS7300-A-J101 study, it was tested in patients with advanced or metastatic solid tumors, without selection for B7-H3 expression. A subgroup analysis of 22 patients with small cell lung cancer (SCLC) showed an ORR of 52.4 (95% CI, 29.8-74.3), a complete response of 4.8%, and a partial response in 47.6%. The median PFS was 5.6 months (95% CI, 3.9-8.1) and median OS was 12.2 months (95% CI, 6.4-not applicable). The most common treatment-emergent adverse events were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%), and decreased appetite (22.7%). (Abstract)

Antibody-drug conjugates (ADC) link a tumor-targeted antibody to a cytotoxic drug through a chemical linker and hold the promise of high potency. This has led to a burgeoning interest in solid tumors, with over 100 clinical trials in progress. Non–small cell lung cancer (NSCLC) is no exception. In 2022, the Food and Drug Administration approved trastuzumab DXd for pretreated NSCLC patients with HER2-mutant tumors. Two others have lung cancer breakthrough therapy designations from the FDA, including patritumab deruxtecan (HER3-DXd) for EGFR-mutant NSCLC and telisotuzumab vedotin for NSCLC that overexpresses c-Met.

At the annual World Conference on Lung Cancer, researchers outlined some of the latest developments in ADCs targeting the antigens HER3, trophoblast cell-surface antigen 2 (TROP-2), and the B7-H3 immunoregulatory protein, as single agents or in combination with immunotherapy. Following the presentations, discussant Helena Linardou, MD, PhD, emphasized the need for pharmacogenomics to predict toxicity and studies to understand resistance mechanisms. “ADCs are a new, rapidly evolving class of therapeutics, and I think that we will all have to be prepared for the future that is coming,” said Dr. Linardou, who is director of the 4th oncology department and the Comprehensive Clinical Trials Center at Metropolitan Hospital in Athens.

Researchers presented four ADC clinical trial updates.
 

Patritumab deruxtecan

Patritumab deruxtecan (Daiichi Sankyo) links a HER3 antibody to the topoisomerase I inhibitor deruxtecan (HER3-DXd). In the open-label, phase 2 HERTHENA-Lung01 trial, it was tested in patients with NSCLC EGFR-activation mutations, which occurs in 14%-38% of NSCLC cases. There are few options for these patients following failure of EGFR tyrosine kinase inhibitor therapy.

The study included 225 patients previously treated with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy who received 5.6 mg/kg of HER3-DXd every 3 weeks. Over a median follow-up of 13.1 months and a median treatment duration of 5.5 months), 29.8% had a confirmed overall response (95% confidence interval, 23.9%-36.2%) with a median duration of 6.4 months (95% CI, 4.9-7.8). The median progression-free survival was 5.5 months (95% CI, 5.1-5.9), and the median OS was 11.9 months (95% CI, 11.2-13.1). The researchers noted similar outcomes among patients with different mechanisms of EGFR TKI resistance. The frequency of adverse events was similar to previous studies, with drug-related adverse events linked to treatment discontinuation of 7.1% interstitial lung disease in 5.3%. Among 30 patients with brain metastases, the confirmed intracranial response rate was 33.3% (95% CI, 17.3%-52.8%).

The study was published simultaneously online in the Journal of Clinical Oncology. (Abstract)
 

Datopotamab deruxtecan

PD-1/PD-L1 inhibitors are the first-line therapy for metastatic NSCLC, but there are efforts to improve outcomes through combination therapy. Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo, AstraZeneca) is an ADC targeting TROP2, and it has been shown in preclinical studies to enhance tumor responses to PD-1/PD-L1 inhibitors. The ADC improved progression-free survival (PFS), compared with docetaxel, in previously treated advanced or metastatic NSCLC.

In an interim analysis of the phase 1b TROPION-Lung04 study, researchers reported results from the combination of Dato-DXd with durvalumab with or without carboplatin. The study included 38 patients, some of whom had previously undergone treatment with immune checkpoint inhibitors. Nineteen patients received the doublet, and 14 received the carboplatin triplet. Grade 3 or higher treatment-emergent adverse events occurred in 42.1% of the doublet group and 71.4% of the triplet group. Interstitial lung disease occurred in 15.8% and 7.1% of the two groups, respectively. The objective response rate was 50.0% in the doublet group and 76.9% in the triplet group. The disease control rate was 92.9% and 92.3%, respectively. Durable responses occurred in both the first-line setting and the overall population. (Abstract)
 

Sacituzumab govitecan

Another ADC being tested with PD-1/PD-L1 inhibitors is sacituzumab govitecan (Trodelvy, Gilead), which has already received FDA approval for metastatic triple-negative breast cancer, pretreated HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer. Like datopotamab, sacituzumab targets TROP-2. Researchers reported preliminary results from the phase 2 EVOKE-02 study, in which the ADC was combined with pembrolizumab for the first-line treatment of metastatic NSCLC. The overall response rate was 56% (95% CI, 42%-69%). Among patients with PD-L1 tumor proportion score (TPS) ≥ 50%, the ORR was 69% (95% CI, 49%-85%) and 44% (95% CI, 26%-62%) among those with TPS < 50%. The disease control rate was 86% (95% CI, 68%-96%) and 78% (95% CI, 60%-91%), respectively. The most frequent treatment-emergent adverse events (TEAEs) were diarrhea, anemia, and asthenia, and 18% of patients discontinued the study drug because of TEAEs. (Abstract)

Ifinatamab deruxtecan

Ifinatamab deruxtecan (Daiichi Sankyo) targets the B7-H3 antigen, which is an immunoregulatory protein that is overexpressed in many tumors. In the DS7300-A-J101 study, it was tested in patients with advanced or metastatic solid tumors, without selection for B7-H3 expression. A subgroup analysis of 22 patients with small cell lung cancer (SCLC) showed an ORR of 52.4 (95% CI, 29.8-74.3), a complete response of 4.8%, and a partial response in 47.6%. The median PFS was 5.6 months (95% CI, 3.9-8.1) and median OS was 12.2 months (95% CI, 6.4-not applicable). The most common treatment-emergent adverse events were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%), and decreased appetite (22.7%). (Abstract)

TOPLINE:

Implementing a post-surgery protocol that has undergone incremental changes over time significantly reduced inpatient and discharge opioid volumes while maintaining pain control after pancreatic cancer surgery.
 

METHODOLOGY:

• To reduce opioid dependence, misuse, and diversion, Centers for Disease Control and Prevention guidelines emphasize strategies to minimize opioid prescribing for managing pain. Still, opioid prescribing following surgery remains common practice.
• In the current study, a team of researchers implemented a recovery care pathway to reduce opioid use among 832 patients undergoing pancreatic resection at a comprehensive cancer center.
• The study evaluated three sequential protocols implemented over a period of about 6 years, from 2016 to 2022.
• In the final version, a standardized three-drug nonopioid bundle (acetaminophen, celecoxib, and methocarbamol) was initiated intravenously in the recovery room, after which the patient was given oral agents on postoperative day 1.
• The primary outcome measure was inpatient and discharge opioid volume in oral morphine equivalents (OMEs) across the three pathways.

TAKEAWAY:

• Opioid use significantly decreased with each sequential pathway refinement.
• For inpatients, total OME decreased by more than 55% across the pathways from a median of 290 mg to 184 mg and finally to 129 mg (P < .001).
• Median discharge OME dropped from 150 mg to 25 mg and then to 0 mg across the pathways (P < .001).
• With the final version of the pathway, more than half of patients (52.5%) had opioid-free discharges, compared with only 7.2% in the first pathway. Pain scores remained stable at 3 or less; the number of postdischarge refill requests was unchanged.

IN PRACTICE:

“Our findings suggest that reduction of postoperative opioid dissemination through opioid-free discharge after pancreatectomy and other major cancer operations may be realistic and feasible by following this no-cost blueprint,” the authors concluded. In an accompanying editorial, Melissa Hogg, MD, from NorthShore University Health System in Evanston, Ill., said the “study inspired me to update our institution’s [early recovery after surgery] protocol to reduce and eliminate opioid prescriptions.”
 

SOURCE:

The study was led by Ching-Wei D. Tzeng, MD, of the University of Texas MD Anderson Cancer Center, Houston. It was published online in JAMA Surgery.
 

LIMITATIONS:

The study evaluated the opioid protocol at a single center, which may limit the generalizability of the findings. The researchers did not receive patient feedback on pain control expectations or postoperative quality of life.
 

DISCLOSURES:

Dr. Tzeng reported receiving consultant fees and a sponsored research agreement from PanTher outside the submitted work. Dr. Hogg reported receiving training and travel funds from Intuitive Money. No other disclosures or outside funding were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Implementing a post-surgery protocol that has undergone incremental changes over time significantly reduced inpatient and discharge opioid volumes while maintaining pain control after pancreatic cancer surgery.
 

METHODOLOGY:

• To reduce opioid dependence, misuse, and diversion, Centers for Disease Control and Prevention guidelines emphasize strategies to minimize opioid prescribing for managing pain. Still, opioid prescribing following surgery remains common practice.
• In the current study, a team of researchers implemented a recovery care pathway to reduce opioid use among 832 patients undergoing pancreatic resection at a comprehensive cancer center.
• The study evaluated three sequential protocols implemented over a period of about 6 years, from 2016 to 2022.
• In the final version, a standardized three-drug nonopioid bundle (acetaminophen, celecoxib, and methocarbamol) was initiated intravenously in the recovery room, after which the patient was given oral agents on postoperative day 1.
• The primary outcome measure was inpatient and discharge opioid volume in oral morphine equivalents (OMEs) across the three pathways.

TAKEAWAY:

• Opioid use significantly decreased with each sequential pathway refinement.
• For inpatients, total OME decreased by more than 55% across the pathways from a median of 290 mg to 184 mg and finally to 129 mg (P < .001).
• Median discharge OME dropped from 150 mg to 25 mg and then to 0 mg across the pathways (P < .001).
• With the final version of the pathway, more than half of patients (52.5%) had opioid-free discharges, compared with only 7.2% in the first pathway. Pain scores remained stable at 3 or less; the number of postdischarge refill requests was unchanged.

IN PRACTICE:

“Our findings suggest that reduction of postoperative opioid dissemination through opioid-free discharge after pancreatectomy and other major cancer operations may be realistic and feasible by following this no-cost blueprint,” the authors concluded. In an accompanying editorial, Melissa Hogg, MD, from NorthShore University Health System in Evanston, Ill., said the “study inspired me to update our institution’s [early recovery after surgery] protocol to reduce and eliminate opioid prescriptions.”
 

SOURCE:

The study was led by Ching-Wei D. Tzeng, MD, of the University of Texas MD Anderson Cancer Center, Houston. It was published online in JAMA Surgery.
 

LIMITATIONS:

The study evaluated the opioid protocol at a single center, which may limit the generalizability of the findings. The researchers did not receive patient feedback on pain control expectations or postoperative quality of life.
 

DISCLOSURES:

Dr. Tzeng reported receiving consultant fees and a sponsored research agreement from PanTher outside the submitted work. Dr. Hogg reported receiving training and travel funds from Intuitive Money. No other disclosures or outside funding were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Implementing a post-surgery protocol that has undergone incremental changes over time significantly reduced inpatient and discharge opioid volumes while maintaining pain control after pancreatic cancer surgery.
 

METHODOLOGY:

• To reduce opioid dependence, misuse, and diversion, Centers for Disease Control and Prevention guidelines emphasize strategies to minimize opioid prescribing for managing pain. Still, opioid prescribing following surgery remains common practice.
• In the current study, a team of researchers implemented a recovery care pathway to reduce opioid use among 832 patients undergoing pancreatic resection at a comprehensive cancer center.
• The study evaluated three sequential protocols implemented over a period of about 6 years, from 2016 to 2022.
• In the final version, a standardized three-drug nonopioid bundle (acetaminophen, celecoxib, and methocarbamol) was initiated intravenously in the recovery room, after which the patient was given oral agents on postoperative day 1.
• The primary outcome measure was inpatient and discharge opioid volume in oral morphine equivalents (OMEs) across the three pathways.

TAKEAWAY:

• Opioid use significantly decreased with each sequential pathway refinement.
• For inpatients, total OME decreased by more than 55% across the pathways from a median of 290 mg to 184 mg and finally to 129 mg (P < .001).
• Median discharge OME dropped from 150 mg to 25 mg and then to 0 mg across the pathways (P < .001).
• With the final version of the pathway, more than half of patients (52.5%) had opioid-free discharges, compared with only 7.2% in the first pathway. Pain scores remained stable at 3 or less; the number of postdischarge refill requests was unchanged.

IN PRACTICE:

“Our findings suggest that reduction of postoperative opioid dissemination through opioid-free discharge after pancreatectomy and other major cancer operations may be realistic and feasible by following this no-cost blueprint,” the authors concluded. In an accompanying editorial, Melissa Hogg, MD, from NorthShore University Health System in Evanston, Ill., said the “study inspired me to update our institution’s [early recovery after surgery] protocol to reduce and eliminate opioid prescriptions.”
 

SOURCE:

The study was led by Ching-Wei D. Tzeng, MD, of the University of Texas MD Anderson Cancer Center, Houston. It was published online in JAMA Surgery.
 

LIMITATIONS:

The study evaluated the opioid protocol at a single center, which may limit the generalizability of the findings. The researchers did not receive patient feedback on pain control expectations or postoperative quality of life.
 

DISCLOSURES:

Dr. Tzeng reported receiving consultant fees and a sponsored research agreement from PanTher outside the submitted work. Dr. Hogg reported receiving training and travel funds from Intuitive Money. No other disclosures or outside funding were reported.

A version of this article appeared on Medscape.com.

SINGAPORE – Heavily pretreated patients with EGFR-mutated non–small cell lung cancer (NSCLC) may experience a clinically meaningful benefit with the antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd), new phase 2 trial results suggest.

In the trial, almost 30% of patients receiving HER3-DXd achieved an objective response, and patients’ median overall survival approached 1 year.

HER3-DXd has “emerged as a promising therapy” in this patient population, “for whom available treatment options provide only limited efficacy,” concluded lead study author Helena A. Yu, MD, from Memorial Sloan Kettering Cancer Center, New York City, who presented findings from the HERTHENA-Lung01 trial at the 2023 World Conference on Lung Cancer.

The results were simultaneously published in the Journal of Clinical Oncology.

Acquired resistance to therapy among heavily pretreated patients with EGFR-mutated NSCLC is “universal,” Dr. Yu explained. The mechanisms of resistance to first-line osimertinib are also “diverse” and hard to identify. Salvage therapies after failed EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy offer “only a limited and transient and clinical benefit,” she said.

And with limited treatment options available to patients resistant to TKIs, there is a “high unmet medical need” for new therapies, said Helena Linardou, MD, PhD, who was not involved in the study.

HER3-DXd consists of a fully human anti-HER3 immunoglobulin G1 monoclonal antibody (patritumab) attached to a topoisomerase I inhibitor payload (DXd) via a tetrapeptide-based cleavable linker.

HER3, Dr. Linardou explained, is a “biologically and clinically important target” in NSCLC. It is highly expressed in NSCLC, upregulated in TKI-resistant EGFR-mutated NSCLC, and is associated with a poor prognosis.

After promising phase 1 data, Dr. Yu and colleagues conducted a phase 2 trial in patients with advanced EGFR-mutated NSCLC who had progressed on systematic therapy and had received EGFR TKI and platinum-based chemotherapy. Patients could have active or previously treated asymptomatic brain metastases.

Patients were initially randomized either to a fixed-dose arm of HER3-DXd 5.6 mg/kg once every 3 weeks or an uptitration arm with doses escalating from 3.2 mg/kg to 4.8 mg/kg to 6.4 mg/kg over three cycles. However, Dr. Yu noted, enrollment in the uptitration arm closed early based on a “benefit-risk assessment.”

The current findings focus on the 225 patients in the fixed-dose arm.

About half of patients had a history of central nervous system metastasis, and patients had a median of three prior lines of systemic therapy. Most patients (92.9%) had previously received a third-generation EGFR TKI, about 40% had received immunotherapy, and all had received platinum-based chemotherapy.

After a median follow-up of 18.9 months, the confirmed objective response rate with HER3-DXd across the whole patient population was 29.8%. The median duration of response was 6.4 months, median progression-free survival was 5.5 months, and median overall survival was 11.9 months.

The results were virtually identical when looking only at patients who had received a third-generation EGFR TKI versus any EGFR TKI. Response rates were also similar regardless of the driver of EGFR TKI resistance.

Among the 30 patients with measurable brain metastases at baseline, 33.3% had a confirmed objective response to therapy. In this group, the disease control rate was 76.7% and the intracranial duration of response was 8.4 months.

To identify biomarkers of response to HER3-DXd, the team stratified the patients by baseline tumor HER3 membrane H-scores. Dr. Yu and colleagues found no differences in the likelihood of having a complete or partial response, stable disease, or progressive disease based on HER3 expression at study entry.

Looking at the safety of the ADC, only 7.1% of patients experienced a treatment-emergent adverse event associated with treatment discontinuation, but close to half of patients (45.3%) experienced a grade 3 or higher treatment-emergent adverse event. Interstitial lung disease, for instance, occurred in 5.3% of patients, including one patient who died.

The safety profile of HER3-DXd in this population appeared to be consistent with previous reports, Dr. Yu noted.

Overall, the findings suggest that “HER3-DXd provided clinically meaningful and durable efficacy” in patients with advanced EGFR-mutant NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy, Dr. Yu said.

“Efficacy was observed across diverse mechanisms of resistance and across a broad range of pretreatment tumor HER3 expression” and the ADC demonstrated “clinically meaningful intracranial antitumor activity,” she added.

Dr. Linardou agreed that the current results suggest that HER3-DXd was associated with a “meaningful and durable efficacy,” including in patients with intracranial metastases, and she pointed to its “easy dosing schedule” and activity across patient subgroups.

However, she noted that, despite the researchers’ best efforts with the data available, “we don’t have a biomarker of activity,” which is a “general issue with ADCs.”

Still, Dr. Linardou said, “HER3 is now a clinically actionable therapeutic target, and this is a great bonus.”

The study was sponsored by Daiichi Sankyo. Dr. Yu declared relationships with AstraZeneca, Daiichi Sankyo, Blueprint Medicines, Janssen, C4 Therapeutics, Cullinan Oncology, Black Diamond Therapeutics, Taiho Oncology, and others. Other authors declare numerous relationships.

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

SINGAPORE – Heavily pretreated patients with EGFR-mutated non–small cell lung cancer (NSCLC) may experience a clinically meaningful benefit with the antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd), new phase 2 trial results suggest.

In the trial, almost 30% of patients receiving HER3-DXd achieved an objective response, and patients’ median overall survival approached 1 year.

HER3-DXd has “emerged as a promising therapy” in this patient population, “for whom available treatment options provide only limited efficacy,” concluded lead study author Helena A. Yu, MD, from Memorial Sloan Kettering Cancer Center, New York City, who presented findings from the HERTHENA-Lung01 trial at the 2023 World Conference on Lung Cancer.

The results were simultaneously published in the Journal of Clinical Oncology.

Acquired resistance to therapy among heavily pretreated patients with EGFR-mutated NSCLC is “universal,” Dr. Yu explained. The mechanisms of resistance to first-line osimertinib are also “diverse” and hard to identify. Salvage therapies after failed EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy offer “only a limited and transient and clinical benefit,” she said.

And with limited treatment options available to patients resistant to TKIs, there is a “high unmet medical need” for new therapies, said Helena Linardou, MD, PhD, who was not involved in the study.

HER3-DXd consists of a fully human anti-HER3 immunoglobulin G1 monoclonal antibody (patritumab) attached to a topoisomerase I inhibitor payload (DXd) via a tetrapeptide-based cleavable linker.

HER3, Dr. Linardou explained, is a “biologically and clinically important target” in NSCLC. It is highly expressed in NSCLC, upregulated in TKI-resistant EGFR-mutated NSCLC, and is associated with a poor prognosis.

After promising phase 1 data, Dr. Yu and colleagues conducted a phase 2 trial in patients with advanced EGFR-mutated NSCLC who had progressed on systematic therapy and had received EGFR TKI and platinum-based chemotherapy. Patients could have active or previously treated asymptomatic brain metastases.

Patients were initially randomized either to a fixed-dose arm of HER3-DXd 5.6 mg/kg once every 3 weeks or an uptitration arm with doses escalating from 3.2 mg/kg to 4.8 mg/kg to 6.4 mg/kg over three cycles. However, Dr. Yu noted, enrollment in the uptitration arm closed early based on a “benefit-risk assessment.”

The current findings focus on the 225 patients in the fixed-dose arm.

About half of patients had a history of central nervous system metastasis, and patients had a median of three prior lines of systemic therapy. Most patients (92.9%) had previously received a third-generation EGFR TKI, about 40% had received immunotherapy, and all had received platinum-based chemotherapy.

After a median follow-up of 18.9 months, the confirmed objective response rate with HER3-DXd across the whole patient population was 29.8%. The median duration of response was 6.4 months, median progression-free survival was 5.5 months, and median overall survival was 11.9 months.

The results were virtually identical when looking only at patients who had received a third-generation EGFR TKI versus any EGFR TKI. Response rates were also similar regardless of the driver of EGFR TKI resistance.

Among the 30 patients with measurable brain metastases at baseline, 33.3% had a confirmed objective response to therapy. In this group, the disease control rate was 76.7% and the intracranial duration of response was 8.4 months.

To identify biomarkers of response to HER3-DXd, the team stratified the patients by baseline tumor HER3 membrane H-scores. Dr. Yu and colleagues found no differences in the likelihood of having a complete or partial response, stable disease, or progressive disease based on HER3 expression at study entry.

Looking at the safety of the ADC, only 7.1% of patients experienced a treatment-emergent adverse event associated with treatment discontinuation, but close to half of patients (45.3%) experienced a grade 3 or higher treatment-emergent adverse event. Interstitial lung disease, for instance, occurred in 5.3% of patients, including one patient who died.

The safety profile of HER3-DXd in this population appeared to be consistent with previous reports, Dr. Yu noted.

Overall, the findings suggest that “HER3-DXd provided clinically meaningful and durable efficacy” in patients with advanced EGFR-mutant NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy, Dr. Yu said.

“Efficacy was observed across diverse mechanisms of resistance and across a broad range of pretreatment tumor HER3 expression” and the ADC demonstrated “clinically meaningful intracranial antitumor activity,” she added.

Dr. Linardou agreed that the current results suggest that HER3-DXd was associated with a “meaningful and durable efficacy,” including in patients with intracranial metastases, and she pointed to its “easy dosing schedule” and activity across patient subgroups.

However, she noted that, despite the researchers’ best efforts with the data available, “we don’t have a biomarker of activity,” which is a “general issue with ADCs.”

Still, Dr. Linardou said, “HER3 is now a clinically actionable therapeutic target, and this is a great bonus.”

The study was sponsored by Daiichi Sankyo. Dr. Yu declared relationships with AstraZeneca, Daiichi Sankyo, Blueprint Medicines, Janssen, C4 Therapeutics, Cullinan Oncology, Black Diamond Therapeutics, Taiho Oncology, and others. Other authors declare numerous relationships.

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

SINGAPORE – Heavily pretreated patients with EGFR-mutated non–small cell lung cancer (NSCLC) may experience a clinically meaningful benefit with the antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd), new phase 2 trial results suggest.

In the trial, almost 30% of patients receiving HER3-DXd achieved an objective response, and patients’ median overall survival approached 1 year.

HER3-DXd has “emerged as a promising therapy” in this patient population, “for whom available treatment options provide only limited efficacy,” concluded lead study author Helena A. Yu, MD, from Memorial Sloan Kettering Cancer Center, New York City, who presented findings from the HERTHENA-Lung01 trial at the 2023 World Conference on Lung Cancer.

The results were simultaneously published in the Journal of Clinical Oncology.

Acquired resistance to therapy among heavily pretreated patients with EGFR-mutated NSCLC is “universal,” Dr. Yu explained. The mechanisms of resistance to first-line osimertinib are also “diverse” and hard to identify. Salvage therapies after failed EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy offer “only a limited and transient and clinical benefit,” she said.

And with limited treatment options available to patients resistant to TKIs, there is a “high unmet medical need” for new therapies, said Helena Linardou, MD, PhD, who was not involved in the study.

HER3-DXd consists of a fully human anti-HER3 immunoglobulin G1 monoclonal antibody (patritumab) attached to a topoisomerase I inhibitor payload (DXd) via a tetrapeptide-based cleavable linker.

HER3, Dr. Linardou explained, is a “biologically and clinically important target” in NSCLC. It is highly expressed in NSCLC, upregulated in TKI-resistant EGFR-mutated NSCLC, and is associated with a poor prognosis.

After promising phase 1 data, Dr. Yu and colleagues conducted a phase 2 trial in patients with advanced EGFR-mutated NSCLC who had progressed on systematic therapy and had received EGFR TKI and platinum-based chemotherapy. Patients could have active or previously treated asymptomatic brain metastases.

Patients were initially randomized either to a fixed-dose arm of HER3-DXd 5.6 mg/kg once every 3 weeks or an uptitration arm with doses escalating from 3.2 mg/kg to 4.8 mg/kg to 6.4 mg/kg over three cycles. However, Dr. Yu noted, enrollment in the uptitration arm closed early based on a “benefit-risk assessment.”

The current findings focus on the 225 patients in the fixed-dose arm.

About half of patients had a history of central nervous system metastasis, and patients had a median of three prior lines of systemic therapy. Most patients (92.9%) had previously received a third-generation EGFR TKI, about 40% had received immunotherapy, and all had received platinum-based chemotherapy.

After a median follow-up of 18.9 months, the confirmed objective response rate with HER3-DXd across the whole patient population was 29.8%. The median duration of response was 6.4 months, median progression-free survival was 5.5 months, and median overall survival was 11.9 months.

The results were virtually identical when looking only at patients who had received a third-generation EGFR TKI versus any EGFR TKI. Response rates were also similar regardless of the driver of EGFR TKI resistance.

Among the 30 patients with measurable brain metastases at baseline, 33.3% had a confirmed objective response to therapy. In this group, the disease control rate was 76.7% and the intracranial duration of response was 8.4 months.

To identify biomarkers of response to HER3-DXd, the team stratified the patients by baseline tumor HER3 membrane H-scores. Dr. Yu and colleagues found no differences in the likelihood of having a complete or partial response, stable disease, or progressive disease based on HER3 expression at study entry.

Looking at the safety of the ADC, only 7.1% of patients experienced a treatment-emergent adverse event associated with treatment discontinuation, but close to half of patients (45.3%) experienced a grade 3 or higher treatment-emergent adverse event. Interstitial lung disease, for instance, occurred in 5.3% of patients, including one patient who died.

The safety profile of HER3-DXd in this population appeared to be consistent with previous reports, Dr. Yu noted.

Overall, the findings suggest that “HER3-DXd provided clinically meaningful and durable efficacy” in patients with advanced EGFR-mutant NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy, Dr. Yu said.

“Efficacy was observed across diverse mechanisms of resistance and across a broad range of pretreatment tumor HER3 expression” and the ADC demonstrated “clinically meaningful intracranial antitumor activity,” she added.

Dr. Linardou agreed that the current results suggest that HER3-DXd was associated with a “meaningful and durable efficacy,” including in patients with intracranial metastases, and she pointed to its “easy dosing schedule” and activity across patient subgroups.

However, she noted that, despite the researchers’ best efforts with the data available, “we don’t have a biomarker of activity,” which is a “general issue with ADCs.”

Still, Dr. Linardou said, “HER3 is now a clinically actionable therapeutic target, and this is a great bonus.”

The study was sponsored by Daiichi Sankyo. Dr. Yu declared relationships with AstraZeneca, Daiichi Sankyo, Blueprint Medicines, Janssen, C4 Therapeutics, Cullinan Oncology, Black Diamond Therapeutics, Taiho Oncology, and others. Other authors declare numerous relationships.

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

The U.S. Food and Drug Administration has approved motixafortide (Aphexda, BioLineRx) in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells for collection and subsequent autologous transplantation in patients with multiple myeloma.

The success of autologous stem cell transplantation (ASCT) depends on adequate mobilization of stem cells during the treatment process. Collection of a sufficient number of stem cells to perform two transplantations is recommended. However, in up to 47% of patients, collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session remains a challenge, BioLineRx explained in a press release today, announcing the approval.

The goal of combining motixafortide with filgrastim is to mobilize stem cells more reliably than filgrastim can alone, with fewer days of apheresis sessions and fewer doses of filgrastim.

“We believe [motixafortide] will play a critical role in addressing unmet needs and introduce a new treatment paradigm for” patients with multiple myeloma, CEO Philip Serlin said in the release.

The drug approval was based on the GENESIS trial, which randomized 122 patients to either motixafortide plus filgrastim or placebo plus filgrastim.

BioLineRx said the trial included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with about 70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.

Motixafortide plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of 6 million or more CD34+ cells/kg within two apheresis sessions, versus 9.5% of patients receiving the placebo plus filgrastim regimen. Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the motixafortide arm and 21.4% in the placebo arm.

However, “the data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted,” the company said.

Serious adverse reactions occurred in 5.4% of patients in the motixafortide arm, including vomiting, injection-site reaction, hypersensitivity reaction, injection-site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions, occurring in more than 20% of patients, were injection site reactions (pain, erythema, and pruritus), pruritus, flushing, and back pain.

Labeling for the subcutaneous injection is available online.

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

The U.S. Food and Drug Administration has approved motixafortide (Aphexda, BioLineRx) in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells for collection and subsequent autologous transplantation in patients with multiple myeloma.

The success of autologous stem cell transplantation (ASCT) depends on adequate mobilization of stem cells during the treatment process. Collection of a sufficient number of stem cells to perform two transplantations is recommended. However, in up to 47% of patients, collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session remains a challenge, BioLineRx explained in a press release today, announcing the approval.

The goal of combining motixafortide with filgrastim is to mobilize stem cells more reliably than filgrastim can alone, with fewer days of apheresis sessions and fewer doses of filgrastim.

“We believe [motixafortide] will play a critical role in addressing unmet needs and introduce a new treatment paradigm for” patients with multiple myeloma, CEO Philip Serlin said in the release.

The drug approval was based on the GENESIS trial, which randomized 122 patients to either motixafortide plus filgrastim or placebo plus filgrastim.

BioLineRx said the trial included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with about 70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.

Motixafortide plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of 6 million or more CD34+ cells/kg within two apheresis sessions, versus 9.5% of patients receiving the placebo plus filgrastim regimen. Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the motixafortide arm and 21.4% in the placebo arm.

However, “the data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted,” the company said.

Serious adverse reactions occurred in 5.4% of patients in the motixafortide arm, including vomiting, injection-site reaction, hypersensitivity reaction, injection-site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions, occurring in more than 20% of patients, were injection site reactions (pain, erythema, and pruritus), pruritus, flushing, and back pain.

Labeling for the subcutaneous injection is available online.

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

The U.S. Food and Drug Administration has approved motixafortide (Aphexda, BioLineRx) in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells for collection and subsequent autologous transplantation in patients with multiple myeloma.

The success of autologous stem cell transplantation (ASCT) depends on adequate mobilization of stem cells during the treatment process. Collection of a sufficient number of stem cells to perform two transplantations is recommended. However, in up to 47% of patients, collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session remains a challenge, BioLineRx explained in a press release today, announcing the approval.

The goal of combining motixafortide with filgrastim is to mobilize stem cells more reliably than filgrastim can alone, with fewer days of apheresis sessions and fewer doses of filgrastim.

“We believe [motixafortide] will play a critical role in addressing unmet needs and introduce a new treatment paradigm for” patients with multiple myeloma, CEO Philip Serlin said in the release.

The drug approval was based on the GENESIS trial, which randomized 122 patients to either motixafortide plus filgrastim or placebo plus filgrastim.

BioLineRx said the trial included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with about 70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.

Motixafortide plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of 6 million or more CD34+ cells/kg within two apheresis sessions, versus 9.5% of patients receiving the placebo plus filgrastim regimen. Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the motixafortide arm and 21.4% in the placebo arm.

However, “the data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted,” the company said.

Serious adverse reactions occurred in 5.4% of patients in the motixafortide arm, including vomiting, injection-site reaction, hypersensitivity reaction, injection-site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions, occurring in more than 20% of patients, were injection site reactions (pain, erythema, and pruritus), pruritus, flushing, and back pain.

Labeling for the subcutaneous injection is available online.

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

Should patients with acute myeloid leukemia (AML) for whom induction therapy fails to induce complete remission proceed to allogeneic hematopoietic stem cell transplant anyway? Or do these patients fare better when they receive an intensive salvage induction regimen to bring them into remission before transplant?

This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.

Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.

“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”

According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.

If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.

The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.

In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.

Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.

At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.

Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.

The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.

These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.

A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.

Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
 

Counterpoint: Aim for complete remission

Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.

The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.

“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.

Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.

A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.

Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.

Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.

It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.

One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.

However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.

“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.

The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Should patients with acute myeloid leukemia (AML) for whom induction therapy fails to induce complete remission proceed to allogeneic hematopoietic stem cell transplant anyway? Or do these patients fare better when they receive an intensive salvage induction regimen to bring them into remission before transplant?

This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.

Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.

“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”

According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.

If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.

The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.

In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.

Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.

At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.

Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.

The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.

These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.

A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.

Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
 

Counterpoint: Aim for complete remission

Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.

The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.

“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.

Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.

A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.

Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.

Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.

It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.

One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.

However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.

“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.

The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Should patients with acute myeloid leukemia (AML) for whom induction therapy fails to induce complete remission proceed to allogeneic hematopoietic stem cell transplant anyway? Or do these patients fare better when they receive an intensive salvage induction regimen to bring them into remission before transplant?

This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.

Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.

“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”

According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.

If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.

The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.

In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.

Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.

At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.

Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.

The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.

These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.

A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.

Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
 

Counterpoint: Aim for complete remission

Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.

The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.

“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.

Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.

A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.

Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.

Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.

It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.

One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.

However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.

“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.

The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A hemostatic powder was shown superior to standard endoscopic treatment in stopping and preventing recurrence of gastrointestinal bleeding caused by malignant tumors.

The findings, published online in Gastroenterology (2023 Jun 3. doi: 10.1053/j.gastro.2023.05.042), come from the largest randomized trial to date of TC-325 (Hemospray, Cook Medical), compared with standard endoscopic hemostatic interventions for tumor bleeding.

For their research, Rapat Pittayanon, MD, of Chulalongkorn University in Bangkok and her colleagues, randomized patients (60% male, mean age 63) with active malignant upper or lower GI bleeding and low disability levels related to their cancers (ECOG score 0-2). The study was conducted at nine hospitals in Thailand.

The 106 patients who passed screening underwent either TC-325 or standard endoscopic hemostasis, which could involve use of thermal or mechanical methods or adrenaline injection, alone or combined with another modality, at the endoscopist’s discretion. Crossover between treatment allocations was permitted if hemostasis was not achieved. Investigators assessed rates of immediate hemostasis and rebleeding at 30 days.

Dr. Pittayanon and colleagues found rebleeding to be significantly lower among TC-325 treated patients, at 2.1%, compared with 21.3% for standard care (odds ratio, 0.09; 95% confidence interval, 0.01-0.80; P = .03). Rates of immediate hemostasis were 100% for TC-325–treated subjects, compared with 68.6% in the conventional-treatment group (OR, 1.45; 95% CI, 0.93-2.29; P < .001).

None of the 55 patients in the TC-325 group underwent crossover treatment, but 15 patients in the standard care group were crossed over to TC-325 after their endoscopic treatment was deemed to have failed. One-fifth of patients who got TC-325 as a crossover treatment developed rebleeding at 30 days, which the investigators surmised was related to mucosal damage incurred during the endoscopic procedure.

The study was not powered to adequately assess survival outcomes. Seven patients in the TC-325 group and four in the conventional care group died before 30 days’ follow-up, and no death was directly related to recurrent tumor bleeding.

“To our knowledge, our trial is the first to show such significant findings in an RCT setting, which now provide a long-awaited efficacious hemostatic approach where one had been lacking when managing patients with malignant GI bleeding,” the investigators wrote in their analysis.

“Perhaps most importantly, this carefully controlled study also highlights the unreliable hemostatic effect of standard endoscopic modalities available for GI tumor hemostasis, with high 30-day rebleeding rates in our patient population.”

Dr. Pittayanon and colleagues noted several limitations of their study. These included the inability to blind patients to an endoscopist, which “may have influenced subsequent management decisions … including the decision to cross over.”

Only in 5 of 15 cases of crossover did the treating endoscopist provide photo evidence of treatment failure as required by the trial’s protocol. Also, the use of adrenaline injection alone was permitted in the study, in contrast to best practice guidelines for endoscopic hemostasis to treat peptic ulcer bleeding. Finally, the study was conducted in Thailand, potentially reducing the generalizability of the results.

The study was funded by King Chulalongkorn Memorial Hospital; the Thai Red Cross; and Chulalongkorn University. Cook Medical donated some of the TC-325 kits used in the study.

One study coauthor, Alan N. Barkun, disclosed consulting work for Medtronic and past paid work for Cook Medical. The remaining authors disclosed no conflicts of interest.

A hemostatic powder was shown superior to standard endoscopic treatment in stopping and preventing recurrence of gastrointestinal bleeding caused by malignant tumors.

The findings, published online in Gastroenterology (2023 Jun 3. doi: 10.1053/j.gastro.2023.05.042), come from the largest randomized trial to date of TC-325 (Hemospray, Cook Medical), compared with standard endoscopic hemostatic interventions for tumor bleeding.

For their research, Rapat Pittayanon, MD, of Chulalongkorn University in Bangkok and her colleagues, randomized patients (60% male, mean age 63) with active malignant upper or lower GI bleeding and low disability levels related to their cancers (ECOG score 0-2). The study was conducted at nine hospitals in Thailand.

The 106 patients who passed screening underwent either TC-325 or standard endoscopic hemostasis, which could involve use of thermal or mechanical methods or adrenaline injection, alone or combined with another modality, at the endoscopist’s discretion. Crossover between treatment allocations was permitted if hemostasis was not achieved. Investigators assessed rates of immediate hemostasis and rebleeding at 30 days.

Dr. Pittayanon and colleagues found rebleeding to be significantly lower among TC-325 treated patients, at 2.1%, compared with 21.3% for standard care (odds ratio, 0.09; 95% confidence interval, 0.01-0.80; P = .03). Rates of immediate hemostasis were 100% for TC-325–treated subjects, compared with 68.6% in the conventional-treatment group (OR, 1.45; 95% CI, 0.93-2.29; P < .001).

None of the 55 patients in the TC-325 group underwent crossover treatment, but 15 patients in the standard care group were crossed over to TC-325 after their endoscopic treatment was deemed to have failed. One-fifth of patients who got TC-325 as a crossover treatment developed rebleeding at 30 days, which the investigators surmised was related to mucosal damage incurred during the endoscopic procedure.

The study was not powered to adequately assess survival outcomes. Seven patients in the TC-325 group and four in the conventional care group died before 30 days’ follow-up, and no death was directly related to recurrent tumor bleeding.

“To our knowledge, our trial is the first to show such significant findings in an RCT setting, which now provide a long-awaited efficacious hemostatic approach where one had been lacking when managing patients with malignant GI bleeding,” the investigators wrote in their analysis.

“Perhaps most importantly, this carefully controlled study also highlights the unreliable hemostatic effect of standard endoscopic modalities available for GI tumor hemostasis, with high 30-day rebleeding rates in our patient population.”

Dr. Pittayanon and colleagues noted several limitations of their study. These included the inability to blind patients to an endoscopist, which “may have influenced subsequent management decisions … including the decision to cross over.”

Only in 5 of 15 cases of crossover did the treating endoscopist provide photo evidence of treatment failure as required by the trial’s protocol. Also, the use of adrenaline injection alone was permitted in the study, in contrast to best practice guidelines for endoscopic hemostasis to treat peptic ulcer bleeding. Finally, the study was conducted in Thailand, potentially reducing the generalizability of the results.

The study was funded by King Chulalongkorn Memorial Hospital; the Thai Red Cross; and Chulalongkorn University. Cook Medical donated some of the TC-325 kits used in the study.

One study coauthor, Alan N. Barkun, disclosed consulting work for Medtronic and past paid work for Cook Medical. The remaining authors disclosed no conflicts of interest.

A hemostatic powder was shown superior to standard endoscopic treatment in stopping and preventing recurrence of gastrointestinal bleeding caused by malignant tumors.

The findings, published online in Gastroenterology (2023 Jun 3. doi: 10.1053/j.gastro.2023.05.042), come from the largest randomized trial to date of TC-325 (Hemospray, Cook Medical), compared with standard endoscopic hemostatic interventions for tumor bleeding.

For their research, Rapat Pittayanon, MD, of Chulalongkorn University in Bangkok and her colleagues, randomized patients (60% male, mean age 63) with active malignant upper or lower GI bleeding and low disability levels related to their cancers (ECOG score 0-2). The study was conducted at nine hospitals in Thailand.

The 106 patients who passed screening underwent either TC-325 or standard endoscopic hemostasis, which could involve use of thermal or mechanical methods or adrenaline injection, alone or combined with another modality, at the endoscopist’s discretion. Crossover between treatment allocations was permitted if hemostasis was not achieved. Investigators assessed rates of immediate hemostasis and rebleeding at 30 days.

Dr. Pittayanon and colleagues found rebleeding to be significantly lower among TC-325 treated patients, at 2.1%, compared with 21.3% for standard care (odds ratio, 0.09; 95% confidence interval, 0.01-0.80; P = .03). Rates of immediate hemostasis were 100% for TC-325–treated subjects, compared with 68.6% in the conventional-treatment group (OR, 1.45; 95% CI, 0.93-2.29; P < .001).

None of the 55 patients in the TC-325 group underwent crossover treatment, but 15 patients in the standard care group were crossed over to TC-325 after their endoscopic treatment was deemed to have failed. One-fifth of patients who got TC-325 as a crossover treatment developed rebleeding at 30 days, which the investigators surmised was related to mucosal damage incurred during the endoscopic procedure.

The study was not powered to adequately assess survival outcomes. Seven patients in the TC-325 group and four in the conventional care group died before 30 days’ follow-up, and no death was directly related to recurrent tumor bleeding.

“To our knowledge, our trial is the first to show such significant findings in an RCT setting, which now provide a long-awaited efficacious hemostatic approach where one had been lacking when managing patients with malignant GI bleeding,” the investigators wrote in their analysis.

“Perhaps most importantly, this carefully controlled study also highlights the unreliable hemostatic effect of standard endoscopic modalities available for GI tumor hemostasis, with high 30-day rebleeding rates in our patient population.”

Dr. Pittayanon and colleagues noted several limitations of their study. These included the inability to blind patients to an endoscopist, which “may have influenced subsequent management decisions … including the decision to cross over.”

Only in 5 of 15 cases of crossover did the treating endoscopist provide photo evidence of treatment failure as required by the trial’s protocol. Also, the use of adrenaline injection alone was permitted in the study, in contrast to best practice guidelines for endoscopic hemostasis to treat peptic ulcer bleeding. Finally, the study was conducted in Thailand, potentially reducing the generalizability of the results.

The study was funded by King Chulalongkorn Memorial Hospital; the Thai Red Cross; and Chulalongkorn University. Cook Medical donated some of the TC-325 kits used in the study.

One study coauthor, Alan N. Barkun, disclosed consulting work for Medtronic and past paid work for Cook Medical. The remaining authors disclosed no conflicts of interest.

TOPLINE:

Regular exercise can significantly reduce a cancer survivor’s mortality from cancer or other causes, a large analysis finds.

METHODOLOGY:

• Following a cancer diagnosis, the impact of exercise on all cause and cause-specific mortality among survivors, and whether the benefit of exercise differs by cancer site, remains unclear.
• To investigate, researchers leveraged data from 11,480 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial.
• Postdiagnosis exercise levels were quantified via a questionnaire. The primary outcome was all-cause mortality; secondary endpoints were deaths from cancer and other causes.
• Cox models estimated cause-specific hazard ratio for all-cause mortality as well as cancer and noncancer mortality based on whether survivors met or did not meet exercise guidelines.
• Meeting national exercise guidelines meant moderate-intensity exercise 4 or more days per week with sessions lasting, on average, 30 minutes or longer; and/or strenuous-intensity exercise 2 or more days per week with sessions lasting, on average, 20 minutes or longer.

TAKEAWAY:

• Overall, 62% of participants were deemed nonexercisers (no exercise or exercise below guidelines) and 38% were classified as exercisers (meeting or exceeding guidelines). After a median follow-up of 16 years from diagnosis, researchers documented 4,665 deaths – 1,940 from cancer and 2,725 from other causes.
• Exercise at recommended levels was associated with “near-universal” all-cause mortality benefit for most cancers represented, including prostate, breast, endometrial, renal, and head and neck cancers.
• In multivariate analysis, compared with nonexercisers, exercisers had a 25% reduced risk of all-cause mortality (HR, 0.75), with the benefit apparent within 5 years and persisting for at least 20 years after diagnosis.
• Exercise was associated with a 21% reduction in cancer mortality and a 28% reduction in mortality from other causes, with more exercise demonstrating a greater benefit on cancer-specific mortality risk.

IN PRACTICE:

Overall, “our findings show exercise is a holistic strategy that may complement contemporary management approaches to further reduce cancer mortality (in select sites) while simultaneously lowering risk of death from other competing causes, which combine to improve all-cause mortality,” the authors conclude. “This benefit was observed within a few years after diagnosis and sustained for at least 20 years.”

SOURCE:

The study, led by Jessica Lavery, MS, Memorial Sloan Kettering Cancer Center, New York, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

Exercise habits were self-reported at one time point, not measured more objectively over time using wearable devices. The population studied was predominantly non-Hispanic White. The researchers could not determine whether exercise habits reflected lower disease and/or treatment-related toxicities as opposed to direct exercise-induced effects or better adherence to a healthy lifestyle.

DISCLOSURES:

Support for the study was provided by AKTIV Against Cancer and grants from Memorial Sloan Kettering Cancer Center and UCLA Jonsson Comprehensive Cancer Center. Disclosures for the study authors are available with the original article.

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

TOPLINE:

Regular exercise can significantly reduce a cancer survivor’s mortality from cancer or other causes, a large analysis finds.

METHODOLOGY:

• Following a cancer diagnosis, the impact of exercise on all cause and cause-specific mortality among survivors, and whether the benefit of exercise differs by cancer site, remains unclear.
• To investigate, researchers leveraged data from 11,480 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial.
• Postdiagnosis exercise levels were quantified via a questionnaire. The primary outcome was all-cause mortality; secondary endpoints were deaths from cancer and other causes.
• Cox models estimated cause-specific hazard ratio for all-cause mortality as well as cancer and noncancer mortality based on whether survivors met or did not meet exercise guidelines.
• Meeting national exercise guidelines meant moderate-intensity exercise 4 or more days per week with sessions lasting, on average, 30 minutes or longer; and/or strenuous-intensity exercise 2 or more days per week with sessions lasting, on average, 20 minutes or longer.

TAKEAWAY:

• Overall, 62% of participants were deemed nonexercisers (no exercise or exercise below guidelines) and 38% were classified as exercisers (meeting or exceeding guidelines). After a median follow-up of 16 years from diagnosis, researchers documented 4,665 deaths – 1,940 from cancer and 2,725 from other causes.
• Exercise at recommended levels was associated with “near-universal” all-cause mortality benefit for most cancers represented, including prostate, breast, endometrial, renal, and head and neck cancers.
• In multivariate analysis, compared with nonexercisers, exercisers had a 25% reduced risk of all-cause mortality (HR, 0.75), with the benefit apparent within 5 years and persisting for at least 20 years after diagnosis.
• Exercise was associated with a 21% reduction in cancer mortality and a 28% reduction in mortality from other causes, with more exercise demonstrating a greater benefit on cancer-specific mortality risk.

IN PRACTICE:

Overall, “our findings show exercise is a holistic strategy that may complement contemporary management approaches to further reduce cancer mortality (in select sites) while simultaneously lowering risk of death from other competing causes, which combine to improve all-cause mortality,” the authors conclude. “This benefit was observed within a few years after diagnosis and sustained for at least 20 years.”

SOURCE:

The study, led by Jessica Lavery, MS, Memorial Sloan Kettering Cancer Center, New York, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

Exercise habits were self-reported at one time point, not measured more objectively over time using wearable devices. The population studied was predominantly non-Hispanic White. The researchers could not determine whether exercise habits reflected lower disease and/or treatment-related toxicities as opposed to direct exercise-induced effects or better adherence to a healthy lifestyle.

DISCLOSURES:

Support for the study was provided by AKTIV Against Cancer and grants from Memorial Sloan Kettering Cancer Center and UCLA Jonsson Comprehensive Cancer Center. Disclosures for the study authors are available with the original article.

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

TOPLINE:

Regular exercise can significantly reduce a cancer survivor’s mortality from cancer or other causes, a large analysis finds.

METHODOLOGY:

• Following a cancer diagnosis, the impact of exercise on all cause and cause-specific mortality among survivors, and whether the benefit of exercise differs by cancer site, remains unclear.
• To investigate, researchers leveraged data from 11,480 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial.
• Postdiagnosis exercise levels were quantified via a questionnaire. The primary outcome was all-cause mortality; secondary endpoints were deaths from cancer and other causes.
• Cox models estimated cause-specific hazard ratio for all-cause mortality as well as cancer and noncancer mortality based on whether survivors met or did not meet exercise guidelines.
• Meeting national exercise guidelines meant moderate-intensity exercise 4 or more days per week with sessions lasting, on average, 30 minutes or longer; and/or strenuous-intensity exercise 2 or more days per week with sessions lasting, on average, 20 minutes or longer.

TAKEAWAY:

• Overall, 62% of participants were deemed nonexercisers (no exercise or exercise below guidelines) and 38% were classified as exercisers (meeting or exceeding guidelines). After a median follow-up of 16 years from diagnosis, researchers documented 4,665 deaths – 1,940 from cancer and 2,725 from other causes.
• Exercise at recommended levels was associated with “near-universal” all-cause mortality benefit for most cancers represented, including prostate, breast, endometrial, renal, and head and neck cancers.
• In multivariate analysis, compared with nonexercisers, exercisers had a 25% reduced risk of all-cause mortality (HR, 0.75), with the benefit apparent within 5 years and persisting for at least 20 years after diagnosis.
• Exercise was associated with a 21% reduction in cancer mortality and a 28% reduction in mortality from other causes, with more exercise demonstrating a greater benefit on cancer-specific mortality risk.

IN PRACTICE:

Overall, “our findings show exercise is a holistic strategy that may complement contemporary management approaches to further reduce cancer mortality (in select sites) while simultaneously lowering risk of death from other competing causes, which combine to improve all-cause mortality,” the authors conclude. “This benefit was observed within a few years after diagnosis and sustained for at least 20 years.”

SOURCE:

The study, led by Jessica Lavery, MS, Memorial Sloan Kettering Cancer Center, New York, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

Exercise habits were self-reported at one time point, not measured more objectively over time using wearable devices. The population studied was predominantly non-Hispanic White. The researchers could not determine whether exercise habits reflected lower disease and/or treatment-related toxicities as opposed to direct exercise-induced effects or better adherence to a healthy lifestyle.

DISCLOSURES:

Support for the study was provided by AKTIV Against Cancer and grants from Memorial Sloan Kettering Cancer Center and UCLA Jonsson Comprehensive Cancer Center. Disclosures for the study authors are available with the original article.

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