TBD Meeting (3035-19)

Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.

Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.

Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.

“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.

“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”

With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.

The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).

In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m² (n = 3), 400 mg/m² (n = 3), 550 mg/m² (n = 7), or 750 mg/m² (n = 3).

In the phase 1b portion, patients received entrectinib at 550 mg/m² (n = 7) – the recommended dose – or 400 mg/m² (n = 6) if they were unable to swallow intact capsules.

Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.

“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”

In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.

Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.

Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).

“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”

Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.

The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.

[email protected]

SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.

Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.

Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.

Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.

“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.

“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”

With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.

The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).

In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m² (n = 3), 400 mg/m² (n = 3), 550 mg/m² (n = 7), or 750 mg/m² (n = 3).

In the phase 1b portion, patients received entrectinib at 550 mg/m² (n = 7) – the recommended dose – or 400 mg/m² (n = 6) if they were unable to swallow intact capsules.

Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.

“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”

In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.

Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.

Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).

“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”

Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.

The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.

[email protected]

SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.

Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.

Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.

Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.

“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.

“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”

With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.

The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).

In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m² (n = 3), 400 mg/m² (n = 3), 550 mg/m² (n = 7), or 750 mg/m² (n = 3).

In the phase 1b portion, patients received entrectinib at 550 mg/m² (n = 7) – the recommended dose – or 400 mg/m² (n = 6) if they were unable to swallow intact capsules.

Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.

“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”

In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.

Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.

Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).

“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”

Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.

The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.

[email protected]

SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.

A low-dose chemotherapy regimen appears safe and effective for older and frail patients with advanced gastroesophageal cancer.

In a phase 3 trial, progression-free survival in patients who received the lowest dose of oxaliplatin and capecitabine was noninferior to progression-free survival in patients who received two higher doses of the combination.

The lowest dose also was associated with better overall treatment utility, which is a composite of clinical benefit, tolerability, quality of life, and patient value.

“[T]his is the largest randomized, controlled trial to date specifically investigating frail or elderly patients with advanced gastroesophageal cancer,” said study investigator Peter S. Hall, PhD, of the University of Edinburgh. “We found that the lowest dose tested was noninferior in terms of progression-free survival, it produced less toxicity, and it had better overall treatment utility.”

These findings are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology. Dr. Hall discussed the findings during a press briefing in advance of the meeting.

The phase 3 trial (ISRCTN44687907) enrolled older and frail patients, aged 51-96 years, with advanced gastroesophageal cancer. Dr. Hall presented data on 514 patients randomized to receive oxaliplatin and capecitabine at one of three dose levels. Dose level A consisted of oxaliplatin given at 130 mg/m² once every 21 days and capecitabine given at 625 mg/m² twice a day every day. Dose level B was 80% of the level A dosage, and dose level C was 60% of the level A dosage. Patients with decreased kidney function received 75% of the allocated capecitabine dose.

The trial’s primary endpoint was noninferiority of progression-free survival at 12 months. Noninferiority was confirmed for level B, compared with level A, with a hazard ratio of 1.09, and for level C, compared with level A, with a hazard ratio of 1.10.

“The lowest dose, the level C dose, had the best overall treatment utility … compared to patients either on level A or level B, and this was due to lower side effects and better quality of life,” Dr. Hall said.

Overall treatment utility outcomes were “good” in 35% of the dose A group, 36% of the dose B group, and 43% of the dose C group. Outcomes were “poor” in 31%, 38%, and 29%, respectively, and outcomes were “intermediate” in 34%, 26%, and 27%, respectively.

To achieve “good” overall treatment utility, patients had to achieve the following six domains: cancer doesn’t progress on scans, oncologist assesses a benefit of treatment, lack of severe toxicity, patient’s global quality of life scores aren’t deteriorating, patient scores the treatment as worthwhile, and the patient says the treatment doesn’t interfere with daily activities.

These results suggest low-dose chemotherapy is feasible for older and frail patients with advanced gastroesophageal cancer, according to Dr. Hall.

“[L]ow-dose treatment may be offered to patients who are suitable for chemotherapy but considered too frail or elderly for a full-dose standard regime, in the confidence that it can produce superior outcomes without compromising cancer control or survival,” Dr. Hall said.

Dr. Hall reported relationships with Eisai, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, and Novartis. The trial was funded by Cancer Research UK and sponsored by the University of Leeds (England).

[email protected]

SOURCE: Hall PS et al. ASCO 2019, Abstract 4006.

A low-dose chemotherapy regimen appears safe and effective for older and frail patients with advanced gastroesophageal cancer.

In a phase 3 trial, progression-free survival in patients who received the lowest dose of oxaliplatin and capecitabine was noninferior to progression-free survival in patients who received two higher doses of the combination.

The lowest dose also was associated with better overall treatment utility, which is a composite of clinical benefit, tolerability, quality of life, and patient value.

“[T]his is the largest randomized, controlled trial to date specifically investigating frail or elderly patients with advanced gastroesophageal cancer,” said study investigator Peter S. Hall, PhD, of the University of Edinburgh. “We found that the lowest dose tested was noninferior in terms of progression-free survival, it produced less toxicity, and it had better overall treatment utility.”

These findings are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology. Dr. Hall discussed the findings during a press briefing in advance of the meeting.

The phase 3 trial (ISRCTN44687907) enrolled older and frail patients, aged 51-96 years, with advanced gastroesophageal cancer. Dr. Hall presented data on 514 patients randomized to receive oxaliplatin and capecitabine at one of three dose levels. Dose level A consisted of oxaliplatin given at 130 mg/m² once every 21 days and capecitabine given at 625 mg/m² twice a day every day. Dose level B was 80% of the level A dosage, and dose level C was 60% of the level A dosage. Patients with decreased kidney function received 75% of the allocated capecitabine dose.

The trial’s primary endpoint was noninferiority of progression-free survival at 12 months. Noninferiority was confirmed for level B, compared with level A, with a hazard ratio of 1.09, and for level C, compared with level A, with a hazard ratio of 1.10.

“The lowest dose, the level C dose, had the best overall treatment utility … compared to patients either on level A or level B, and this was due to lower side effects and better quality of life,” Dr. Hall said.

Overall treatment utility outcomes were “good” in 35% of the dose A group, 36% of the dose B group, and 43% of the dose C group. Outcomes were “poor” in 31%, 38%, and 29%, respectively, and outcomes were “intermediate” in 34%, 26%, and 27%, respectively.

To achieve “good” overall treatment utility, patients had to achieve the following six domains: cancer doesn’t progress on scans, oncologist assesses a benefit of treatment, lack of severe toxicity, patient’s global quality of life scores aren’t deteriorating, patient scores the treatment as worthwhile, and the patient says the treatment doesn’t interfere with daily activities.

These results suggest low-dose chemotherapy is feasible for older and frail patients with advanced gastroesophageal cancer, according to Dr. Hall.

“[L]ow-dose treatment may be offered to patients who are suitable for chemotherapy but considered too frail or elderly for a full-dose standard regime, in the confidence that it can produce superior outcomes without compromising cancer control or survival,” Dr. Hall said.

Dr. Hall reported relationships with Eisai, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, and Novartis. The trial was funded by Cancer Research UK and sponsored by the University of Leeds (England).

[email protected]

SOURCE: Hall PS et al. ASCO 2019, Abstract 4006.

A low-dose chemotherapy regimen appears safe and effective for older and frail patients with advanced gastroesophageal cancer.

In a phase 3 trial, progression-free survival in patients who received the lowest dose of oxaliplatin and capecitabine was noninferior to progression-free survival in patients who received two higher doses of the combination.

The lowest dose also was associated with better overall treatment utility, which is a composite of clinical benefit, tolerability, quality of life, and patient value.

“[T]his is the largest randomized, controlled trial to date specifically investigating frail or elderly patients with advanced gastroesophageal cancer,” said study investigator Peter S. Hall, PhD, of the University of Edinburgh. “We found that the lowest dose tested was noninferior in terms of progression-free survival, it produced less toxicity, and it had better overall treatment utility.”

These findings are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology. Dr. Hall discussed the findings during a press briefing in advance of the meeting.

The phase 3 trial (ISRCTN44687907) enrolled older and frail patients, aged 51-96 years, with advanced gastroesophageal cancer. Dr. Hall presented data on 514 patients randomized to receive oxaliplatin and capecitabine at one of three dose levels. Dose level A consisted of oxaliplatin given at 130 mg/m² once every 21 days and capecitabine given at 625 mg/m² twice a day every day. Dose level B was 80% of the level A dosage, and dose level C was 60% of the level A dosage. Patients with decreased kidney function received 75% of the allocated capecitabine dose.

The trial’s primary endpoint was noninferiority of progression-free survival at 12 months. Noninferiority was confirmed for level B, compared with level A, with a hazard ratio of 1.09, and for level C, compared with level A, with a hazard ratio of 1.10.

“The lowest dose, the level C dose, had the best overall treatment utility … compared to patients either on level A or level B, and this was due to lower side effects and better quality of life,” Dr. Hall said.

Overall treatment utility outcomes were “good” in 35% of the dose A group, 36% of the dose B group, and 43% of the dose C group. Outcomes were “poor” in 31%, 38%, and 29%, respectively, and outcomes were “intermediate” in 34%, 26%, and 27%, respectively.

To achieve “good” overall treatment utility, patients had to achieve the following six domains: cancer doesn’t progress on scans, oncologist assesses a benefit of treatment, lack of severe toxicity, patient’s global quality of life scores aren’t deteriorating, patient scores the treatment as worthwhile, and the patient says the treatment doesn’t interfere with daily activities.

These results suggest low-dose chemotherapy is feasible for older and frail patients with advanced gastroesophageal cancer, according to Dr. Hall.

“[L]ow-dose treatment may be offered to patients who are suitable for chemotherapy but considered too frail or elderly for a full-dose standard regime, in the confidence that it can produce superior outcomes without compromising cancer control or survival,” Dr. Hall said.

Dr. Hall reported relationships with Eisai, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, and Novartis. The trial was funded by Cancer Research UK and sponsored by the University of Leeds (England).

[email protected]

SOURCE: Hall PS et al. ASCO 2019, Abstract 4006.

Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.

At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.

However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.

These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.

A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.

With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.

The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.

In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.

Safety

Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.

The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.

Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
 

Efficacy

“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”

In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.

In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.

“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”

Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.

[email protected]

SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.

Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.

At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.

However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.

These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.

A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.

With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.

The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.

In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.

Safety

Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.

The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.

Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
 

Efficacy

“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”

In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.

In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.

“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”

Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.

[email protected]

SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.

Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.

At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.

However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.

These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.

A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.

With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.

The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.

In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.

Safety

Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.

The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.

Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
 

Efficacy

“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”

In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.

In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.

“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”

Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.

[email protected]

SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.

A balanced, low-fat diet was associated with a lower risk of death from breast cancer in a large cohort of postmenopausal women who had no previous history of breast cancer.

Researchers studied nearly 49,000 postmenopausal women and found a 21% lower risk of death from breast cancer among women who followed the balanced, low-fat diet, compared with women who followed their normal diet.

This research is scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Rowan Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center in Torrance, Calif., discussed the research during a press briefing in advance of the meeting.
 

About the study

The research is part of the Woman’s Health Initiative (NCT00000611), which is focused on investigating methods for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women.

This trial enrolled 48,835 postmenopausal women, ages 50-79 years, with no history of breast cancer and normal mammograms at enrollment. From 1993 to 1998, the women were randomized to the study diet (n = 19,541) or their normal diet (n = 29,294).

With the normal diet, fat accounted for 32% or more of subjects’ daily calories. With the study diet, the goal was to reduce fat consumption to 20% or less of caloric intake. The study diet also required at least one daily serving of vegetables, fruits, and grains.

Dr. Chlebowski said the study diet is similar to DASH (Dietary Approaches to Stop Hypertension), but is slightly more focused on lowering fat intake.
 

Diet adherence

Subjects followed the study diet for a median of 8.5 years, and the median cumulative follow-up was 19.6 years.

Dr. Chlebowski noted that most women on the study diet were not able to reduce their daily fat consumption to the 20% goal. They did reduce fat consumption to 24.5% overall, which increased to 29% at the end of the intervention.

In the study-diet group, there was an average weight loss of 3%, significantly different from that of the normal-diet group (P less than .001).

Dr. Chlebowski said the weight loss indicates that subjects did adhere to the study diet, at least in part, as there was no change in physical activity among study participants. Furthermore, the researchers have evidence after 1 year that suggests subjects were incorporating more fruits and vegetables into their diets.
 

Breast cancer and death

At a median follow-up of 19.6 years, there were 3,374 cases of breast cancer, 1,011 deaths, and 383 deaths attributed to breast cancer.

The risk of death from breast cancer was significantly lower in the study-diet group than in the normal-diet group. The hazard ratio was 0.79 (95% confidence interval, 0.64-0.97; P = .025).

The risk of death (from any cause) after breast cancer was significantly lower in the study diet group as well, with a hazard ratio of 0.85 (95% confidence interval, 0.74-0.96; P = .01).

“Adoption of a low-fat dietary pattern reduces the risk of death from breast cancer in postmenopausal women,” Dr. Chlebowski said. “To our review, this is the only study providing randomized clinical trial evidence that an intervention can reduce a woman’s risk of dying from breast cancer.”

Dr. Chlebowski noted that the researchers have blood samples from all subjects enrolled in this study. The researchers plan to analyze those samples to further explore how the study diet affected the women and determine which components of the diet account for which effects.

The National Institutes of Health funded the study. The researchers disclosed relationships with Novartis, Pfizer, Amgen, AstraZeneca, Immunomedics, Metastat, Bayer, and Genentech/Roche.

SOURCE: Chlebowski R. et al. ASCO 2019. Abstract 520.

A balanced, low-fat diet was associated with a lower risk of death from breast cancer in a large cohort of postmenopausal women who had no previous history of breast cancer.

Researchers studied nearly 49,000 postmenopausal women and found a 21% lower risk of death from breast cancer among women who followed the balanced, low-fat diet, compared with women who followed their normal diet.

This research is scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Rowan Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center in Torrance, Calif., discussed the research during a press briefing in advance of the meeting.
 

About the study

The research is part of the Woman’s Health Initiative (NCT00000611), which is focused on investigating methods for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women.

This trial enrolled 48,835 postmenopausal women, ages 50-79 years, with no history of breast cancer and normal mammograms at enrollment. From 1993 to 1998, the women were randomized to the study diet (n = 19,541) or their normal diet (n = 29,294).

With the normal diet, fat accounted for 32% or more of subjects’ daily calories. With the study diet, the goal was to reduce fat consumption to 20% or less of caloric intake. The study diet also required at least one daily serving of vegetables, fruits, and grains.

Dr. Chlebowski said the study diet is similar to DASH (Dietary Approaches to Stop Hypertension), but is slightly more focused on lowering fat intake.
 

Diet adherence

Subjects followed the study diet for a median of 8.5 years, and the median cumulative follow-up was 19.6 years.

Dr. Chlebowski noted that most women on the study diet were not able to reduce their daily fat consumption to the 20% goal. They did reduce fat consumption to 24.5% overall, which increased to 29% at the end of the intervention.

In the study-diet group, there was an average weight loss of 3%, significantly different from that of the normal-diet group (P less than .001).

Dr. Chlebowski said the weight loss indicates that subjects did adhere to the study diet, at least in part, as there was no change in physical activity among study participants. Furthermore, the researchers have evidence after 1 year that suggests subjects were incorporating more fruits and vegetables into their diets.
 

Breast cancer and death

At a median follow-up of 19.6 years, there were 3,374 cases of breast cancer, 1,011 deaths, and 383 deaths attributed to breast cancer.

The risk of death from breast cancer was significantly lower in the study-diet group than in the normal-diet group. The hazard ratio was 0.79 (95% confidence interval, 0.64-0.97; P = .025).

The risk of death (from any cause) after breast cancer was significantly lower in the study diet group as well, with a hazard ratio of 0.85 (95% confidence interval, 0.74-0.96; P = .01).

“Adoption of a low-fat dietary pattern reduces the risk of death from breast cancer in postmenopausal women,” Dr. Chlebowski said. “To our review, this is the only study providing randomized clinical trial evidence that an intervention can reduce a woman’s risk of dying from breast cancer.”

Dr. Chlebowski noted that the researchers have blood samples from all subjects enrolled in this study. The researchers plan to analyze those samples to further explore how the study diet affected the women and determine which components of the diet account for which effects.

The National Institutes of Health funded the study. The researchers disclosed relationships with Novartis, Pfizer, Amgen, AstraZeneca, Immunomedics, Metastat, Bayer, and Genentech/Roche.

SOURCE: Chlebowski R. et al. ASCO 2019. Abstract 520.

A balanced, low-fat diet was associated with a lower risk of death from breast cancer in a large cohort of postmenopausal women who had no previous history of breast cancer.

Researchers studied nearly 49,000 postmenopausal women and found a 21% lower risk of death from breast cancer among women who followed the balanced, low-fat diet, compared with women who followed their normal diet.

This research is scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Rowan Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center in Torrance, Calif., discussed the research during a press briefing in advance of the meeting.
 

About the study

The research is part of the Woman’s Health Initiative (NCT00000611), which is focused on investigating methods for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women.

This trial enrolled 48,835 postmenopausal women, ages 50-79 years, with no history of breast cancer and normal mammograms at enrollment. From 1993 to 1998, the women were randomized to the study diet (n = 19,541) or their normal diet (n = 29,294).

With the normal diet, fat accounted for 32% or more of subjects’ daily calories. With the study diet, the goal was to reduce fat consumption to 20% or less of caloric intake. The study diet also required at least one daily serving of vegetables, fruits, and grains.

Dr. Chlebowski said the study diet is similar to DASH (Dietary Approaches to Stop Hypertension), but is slightly more focused on lowering fat intake.
 

Diet adherence

Subjects followed the study diet for a median of 8.5 years, and the median cumulative follow-up was 19.6 years.

Dr. Chlebowski noted that most women on the study diet were not able to reduce their daily fat consumption to the 20% goal. They did reduce fat consumption to 24.5% overall, which increased to 29% at the end of the intervention.

In the study-diet group, there was an average weight loss of 3%, significantly different from that of the normal-diet group (P less than .001).

Dr. Chlebowski said the weight loss indicates that subjects did adhere to the study diet, at least in part, as there was no change in physical activity among study participants. Furthermore, the researchers have evidence after 1 year that suggests subjects were incorporating more fruits and vegetables into their diets.
 

Breast cancer and death

At a median follow-up of 19.6 years, there were 3,374 cases of breast cancer, 1,011 deaths, and 383 deaths attributed to breast cancer.

The risk of death from breast cancer was significantly lower in the study-diet group than in the normal-diet group. The hazard ratio was 0.79 (95% confidence interval, 0.64-0.97; P = .025).

The risk of death (from any cause) after breast cancer was significantly lower in the study diet group as well, with a hazard ratio of 0.85 (95% confidence interval, 0.74-0.96; P = .01).

“Adoption of a low-fat dietary pattern reduces the risk of death from breast cancer in postmenopausal women,” Dr. Chlebowski said. “To our review, this is the only study providing randomized clinical trial evidence that an intervention can reduce a woman’s risk of dying from breast cancer.”

Dr. Chlebowski noted that the researchers have blood samples from all subjects enrolled in this study. The researchers plan to analyze those samples to further explore how the study diet affected the women and determine which components of the diet account for which effects.

The National Institutes of Health funded the study. The researchers disclosed relationships with Novartis, Pfizer, Amgen, AstraZeneca, Immunomedics, Metastat, Bayer, and Genentech/Roche.

SOURCE: Chlebowski R. et al. ASCO 2019. Abstract 520.