2015 ASCO Annual Meeting

CHICAGO – Tumors that carry a genetic signature known as mismatch repair deficiency are highly responsive to immune checkpoint blockade with pembrolizumab, according to results from a small proof-of-concept study.

“This is the first study to use genetics in a prospective manner to guide immunotherapy,” study author Dr. Dung T. Le said in a press conference at the annual meeting of the American Society of Clinical Oncology.

The phase II study, also published online May 30 in the New England Journal of Medicine, enrolled three cohorts, all of which had previously treated metastatic cancer. Pembrolizumab (Keytruda) 10 mg/kg was given intravenously every two weeks.

An objective response was observed in 62% of 25 patients with mismatch repair-deficient colorectal cancer versus none of the 25 patients with mismatch repair-proficient colorectal cancer, she said.

Disease control rates, which also included stable disease for at least 12 weeks, were 92% vs. 16%, respectively.

In a third cohort of 21 patients with a variety of mismatch repair-deficient cancers including pancreatic/bile duct, uterine, small bowel, stomach, and prostate, the response rate was 60% and disease control rate 70%.

Median overall survival has not been reached in the mismatch repair-deficient cohorts, with some patients continuing to respond to the immunotherapy drug for more than a year Dr. Le, with the Johns Hopkins Kimmel Cancer Center in Baltimore, said. Median overall survival was about 7.6 months in the mismatch repair-proficient colorectal cohort.

“These data suggest that genomics is more influential than histology for mismatch repair-deficient tumors when treated with anti-PD-1,” she said.

Defects in mismatch repair genes disable cells’ ability to repair errors in the DNA replication process. As a result, tumors deficient in mismatch repair proteins produce hundreds to thousands of mutations. Immunotherapy may work best in patients with more mutations in their tumors because multiple mutations trigger production of more abnormal proteins in cancer cells, and in turn prompt the immune system to mount a bigger response.

Indeed, higher somatic mutation loads were associated with better response and prolonged progression free-survival. On average, mismatch repair-deficient tumors had about 1,700 mutations vs. about 70 mutations in mismatch repair-proficient tumors (P = .007), Dr. Le said.

“Seventeen-hundred mutations: that’s like you put a red flag on the cancer cell and say to the immune system, ‘Here I am,’ ” press conference moderator Dr. Lynn Schuchter, chief of hematology-oncology at University of Pennsylvania in Philadelphia, remarked to reporters.

The study was funded by Swim Across America, The Commonwealth Fund, The Ludwig Center at Johns Hopkins, and the National Institutes of Health. Merck provided the study drug. Personal Genome Diagnostics performed the sequencing analysis. Dr. Le reported having no financial disclosures. Dr. Schuchter reported institutional research funding from Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Merck, and Roche.

pwendling@frontlinemedcom.com

CHICAGO – Tumors that carry a genetic signature known as mismatch repair deficiency are highly responsive to immune checkpoint blockade with pembrolizumab, according to results from a small proof-of-concept study.

“This is the first study to use genetics in a prospective manner to guide immunotherapy,” study author Dr. Dung T. Le said in a press conference at the annual meeting of the American Society of Clinical Oncology.

The phase II study, also published online May 30 in the New England Journal of Medicine, enrolled three cohorts, all of which had previously treated metastatic cancer. Pembrolizumab (Keytruda) 10 mg/kg was given intravenously every two weeks.

An objective response was observed in 62% of 25 patients with mismatch repair-deficient colorectal cancer versus none of the 25 patients with mismatch repair-proficient colorectal cancer, she said.

Disease control rates, which also included stable disease for at least 12 weeks, were 92% vs. 16%, respectively.

In a third cohort of 21 patients with a variety of mismatch repair-deficient cancers including pancreatic/bile duct, uterine, small bowel, stomach, and prostate, the response rate was 60% and disease control rate 70%.

Median overall survival has not been reached in the mismatch repair-deficient cohorts, with some patients continuing to respond to the immunotherapy drug for more than a year Dr. Le, with the Johns Hopkins Kimmel Cancer Center in Baltimore, said. Median overall survival was about 7.6 months in the mismatch repair-proficient colorectal cohort.

“These data suggest that genomics is more influential than histology for mismatch repair-deficient tumors when treated with anti-PD-1,” she said.

Defects in mismatch repair genes disable cells’ ability to repair errors in the DNA replication process. As a result, tumors deficient in mismatch repair proteins produce hundreds to thousands of mutations. Immunotherapy may work best in patients with more mutations in their tumors because multiple mutations trigger production of more abnormal proteins in cancer cells, and in turn prompt the immune system to mount a bigger response.

Indeed, higher somatic mutation loads were associated with better response and prolonged progression free-survival. On average, mismatch repair-deficient tumors had about 1,700 mutations vs. about 70 mutations in mismatch repair-proficient tumors (P = .007), Dr. Le said.

“Seventeen-hundred mutations: that’s like you put a red flag on the cancer cell and say to the immune system, ‘Here I am,’ ” press conference moderator Dr. Lynn Schuchter, chief of hematology-oncology at University of Pennsylvania in Philadelphia, remarked to reporters.

The study was funded by Swim Across America, The Commonwealth Fund, The Ludwig Center at Johns Hopkins, and the National Institutes of Health. Merck provided the study drug. Personal Genome Diagnostics performed the sequencing analysis. Dr. Le reported having no financial disclosures. Dr. Schuchter reported institutional research funding from Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Merck, and Roche.

pwendling@frontlinemedcom.com

CHICAGO – Tumors that carry a genetic signature known as mismatch repair deficiency are highly responsive to immune checkpoint blockade with pembrolizumab, according to results from a small proof-of-concept study.

“This is the first study to use genetics in a prospective manner to guide immunotherapy,” study author Dr. Dung T. Le said in a press conference at the annual meeting of the American Society of Clinical Oncology.

The phase II study, also published online May 30 in the New England Journal of Medicine, enrolled three cohorts, all of which had previously treated metastatic cancer. Pembrolizumab (Keytruda) 10 mg/kg was given intravenously every two weeks.

An objective response was observed in 62% of 25 patients with mismatch repair-deficient colorectal cancer versus none of the 25 patients with mismatch repair-proficient colorectal cancer, she said.

Disease control rates, which also included stable disease for at least 12 weeks, were 92% vs. 16%, respectively.

In a third cohort of 21 patients with a variety of mismatch repair-deficient cancers including pancreatic/bile duct, uterine, small bowel, stomach, and prostate, the response rate was 60% and disease control rate 70%.

Median overall survival has not been reached in the mismatch repair-deficient cohorts, with some patients continuing to respond to the immunotherapy drug for more than a year Dr. Le, with the Johns Hopkins Kimmel Cancer Center in Baltimore, said. Median overall survival was about 7.6 months in the mismatch repair-proficient colorectal cohort.

“These data suggest that genomics is more influential than histology for mismatch repair-deficient tumors when treated with anti-PD-1,” she said.

Defects in mismatch repair genes disable cells’ ability to repair errors in the DNA replication process. As a result, tumors deficient in mismatch repair proteins produce hundreds to thousands of mutations. Immunotherapy may work best in patients with more mutations in their tumors because multiple mutations trigger production of more abnormal proteins in cancer cells, and in turn prompt the immune system to mount a bigger response.

Indeed, higher somatic mutation loads were associated with better response and prolonged progression free-survival. On average, mismatch repair-deficient tumors had about 1,700 mutations vs. about 70 mutations in mismatch repair-proficient tumors (P = .007), Dr. Le said.

“Seventeen-hundred mutations: that’s like you put a red flag on the cancer cell and say to the immune system, ‘Here I am,’ ” press conference moderator Dr. Lynn Schuchter, chief of hematology-oncology at University of Pennsylvania in Philadelphia, remarked to reporters.

The study was funded by Swim Across America, The Commonwealth Fund, The Ludwig Center at Johns Hopkins, and the National Institutes of Health. Merck provided the study drug. Personal Genome Diagnostics performed the sequencing analysis. Dr. Le reported having no financial disclosures. Dr. Schuchter reported institutional research funding from Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Merck, and Roche.

pwendling@frontlinemedcom.com

Dr. Maurie Markman picks the upcoming ASCO presentations he anticipates to be the most interesting in gynecologic research.

• 5510 Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: Interim results from a phase Ib study.

• 5505 Retrospective analysis of candidate predictive tumor biomarkers (BMs) for efficacy in the GOG-0218 trial evaluating front-line carboplatin–paclitaxel (CP) ± bevacizumab (BEV) for epithelial ovarian cancer (EOC).

• 5506 An international, biomarker-directed, randomized, phase II trial of AZD1775 plus paclitaxel and carboplatin (P/C) for the treatment of women with platinum-sensitive, TP53-mutant ovarian cancer.

• 5508 Results of ARIEL2: A phase II trial to prospectively identify ovarian cancer patients likely to respond to rucaparib using tumor genetic analysis.

• 5503 Impact of trebananib plus weekly paclitaxel on overall survival (OS) in patients (pts) with recurrent ovarian cancer and ascites: Results from the phase III TRINOVA-1 study.

• 5502 Randomized phase II trial of carboplatin-paclitaxel (CP) compared to carboplatin-paclitaxel-bevacizumab (CP-B) in advanced (stage III-IV) or recurrent endometrial cancer: The MITO END-2 trial.

Dr. Maurie Markman is president, medicine and science, Cancer Treatment Centers of America.

Dr. Maurie Markman picks the upcoming ASCO presentations he anticipates to be the most interesting in gynecologic research.

• 5510 Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: Interim results from a phase Ib study.

• 5505 Retrospective analysis of candidate predictive tumor biomarkers (BMs) for efficacy in the GOG-0218 trial evaluating front-line carboplatin–paclitaxel (CP) ± bevacizumab (BEV) for epithelial ovarian cancer (EOC).

• 5506 An international, biomarker-directed, randomized, phase II trial of AZD1775 plus paclitaxel and carboplatin (P/C) for the treatment of women with platinum-sensitive, TP53-mutant ovarian cancer.

• 5508 Results of ARIEL2: A phase II trial to prospectively identify ovarian cancer patients likely to respond to rucaparib using tumor genetic analysis.

• 5503 Impact of trebananib plus weekly paclitaxel on overall survival (OS) in patients (pts) with recurrent ovarian cancer and ascites: Results from the phase III TRINOVA-1 study.

• 5502 Randomized phase II trial of carboplatin-paclitaxel (CP) compared to carboplatin-paclitaxel-bevacizumab (CP-B) in advanced (stage III-IV) or recurrent endometrial cancer: The MITO END-2 trial.

Dr. Maurie Markman is president, medicine and science, Cancer Treatment Centers of America.

Dr. Maurie Markman picks the upcoming ASCO presentations he anticipates to be the most interesting in gynecologic research.

• 5510 Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: Interim results from a phase Ib study.

• 5505 Retrospective analysis of candidate predictive tumor biomarkers (BMs) for efficacy in the GOG-0218 trial evaluating front-line carboplatin–paclitaxel (CP) ± bevacizumab (BEV) for epithelial ovarian cancer (EOC).

• 5506 An international, biomarker-directed, randomized, phase II trial of AZD1775 plus paclitaxel and carboplatin (P/C) for the treatment of women with platinum-sensitive, TP53-mutant ovarian cancer.

• 5508 Results of ARIEL2: A phase II trial to prospectively identify ovarian cancer patients likely to respond to rucaparib using tumor genetic analysis.

• 5503 Impact of trebananib plus weekly paclitaxel on overall survival (OS) in patients (pts) with recurrent ovarian cancer and ascites: Results from the phase III TRINOVA-1 study.

• 5502 Randomized phase II trial of carboplatin-paclitaxel (CP) compared to carboplatin-paclitaxel-bevacizumab (CP-B) in advanced (stage III-IV) or recurrent endometrial cancer: The MITO END-2 trial.

Dr. Maurie Markman is president, medicine and science, Cancer Treatment Centers of America.

Dr. Johanna Bendell picks the upcoming ASCO presentations she anticipates to be the most interesting in gastrointestinal research.

• 3504 Impact of aspirin as secondary prevention in an unselected cohort of 25,644 patients with colorectal cancer: A population-based study.

• 3503 Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance).

Dr. Johanna Bendell is the director, GI Oncology Research, and associate director, drug development unit, Sarah Cannon Research Institute, Nashville, Tenn.

Dr. Johanna Bendell picks the upcoming ASCO presentations she anticipates to be the most interesting in gastrointestinal research.

• 3504 Impact of aspirin as secondary prevention in an unselected cohort of 25,644 patients with colorectal cancer: A population-based study.

• 3503 Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance).

Dr. Johanna Bendell is the director, GI Oncology Research, and associate director, drug development unit, Sarah Cannon Research Institute, Nashville, Tenn.

Dr. Johanna Bendell picks the upcoming ASCO presentations she anticipates to be the most interesting in gastrointestinal research.

• 3504 Impact of aspirin as secondary prevention in an unselected cohort of 25,644 patients with colorectal cancer: A population-based study.

• 3503 Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance).

Dr. Johanna Bendell is the director, GI Oncology Research, and associate director, drug development unit, Sarah Cannon Research Institute, Nashville, Tenn.

Dr. Walter M. Stadler picks the upcoming ASCO presentations he anticipates to be the most interesting in genitourinary research.

• 4501 A phase Ia study of MPDL3280A (anti-PDL1): Updated response and survival data in urothelial bladder cancer (UBC).

• 4502 Pembrolizumab (MK-3475) for advanced urothelial cancer: Updated results and biomarker analysis from KEYNOTE-012.

• 4505 A phase II/III, double-blind, randomized trial comparing maintenance lapatinib with placebo after first-line chemotherapy in HER1/2 positive metastatic bladder cancer patients.

• 4509 Identification of efficacy biomarkers in a large metastatic renal cell carcinoma (mRCC) cohort through next generation sequencing (NGS): Results from RECORD-3.

• 4516Expanded cohort results from CheckMate 016: A phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC).

• 5001Docetaxel and/or zoledronic acid for hormone-naive prostate cancer: First overall survival results from STAMPEDE (NCT00268476). The Oncology Report covered this study following a pre-meeting press conference.

• LBA5002A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521).

• 5000The Prostate Cancer Working Group 3 (PCWG3) consensus for trials in castration-resistant prostate cancer (CRPC).

• 5003Characterization of neuroendocrine prostate cancer (NEPC) in patients with metastatic castration resistant prostate cancer (mCRPC) resistant to abiraterone (Abi) or enzalutamide (Enz): Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).

• 5004Defining a molecular subclass of treatment resistant prostate cancer.

• 5007 TROG 03.06 and VCOG PR 01-03: The “timing of androgen deprivation therapy in prostate cancer patients with a rising PSA (TOAD)” collaborative randomized phase III trial.

Dr. Walter M. Stadler is the Fred C. Buffett Professor of Medicine and Surgery; associate dean for clinical research; chief, section of hematology/oncology; and director, genitourinary program, University of Chicago.

Dr. Walter M. Stadler picks the upcoming ASCO presentations he anticipates to be the most interesting in genitourinary research.

• 4501 A phase Ia study of MPDL3280A (anti-PDL1): Updated response and survival data in urothelial bladder cancer (UBC).

• 4502 Pembrolizumab (MK-3475) for advanced urothelial cancer: Updated results and biomarker analysis from KEYNOTE-012.

• 4505 A phase II/III, double-blind, randomized trial comparing maintenance lapatinib with placebo after first-line chemotherapy in HER1/2 positive metastatic bladder cancer patients.

• 4509 Identification of efficacy biomarkers in a large metastatic renal cell carcinoma (mRCC) cohort through next generation sequencing (NGS): Results from RECORD-3.

• 4516Expanded cohort results from CheckMate 016: A phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC).

• 5001Docetaxel and/or zoledronic acid for hormone-naive prostate cancer: First overall survival results from STAMPEDE (NCT00268476). The Oncology Report covered this study following a pre-meeting press conference.

• LBA5002A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521).

• 5000The Prostate Cancer Working Group 3 (PCWG3) consensus for trials in castration-resistant prostate cancer (CRPC).

• 5003Characterization of neuroendocrine prostate cancer (NEPC) in patients with metastatic castration resistant prostate cancer (mCRPC) resistant to abiraterone (Abi) or enzalutamide (Enz): Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).

• 5004Defining a molecular subclass of treatment resistant prostate cancer.

• 5007 TROG 03.06 and VCOG PR 01-03: The “timing of androgen deprivation therapy in prostate cancer patients with a rising PSA (TOAD)” collaborative randomized phase III trial.

Dr. Walter M. Stadler is the Fred C. Buffett Professor of Medicine and Surgery; associate dean for clinical research; chief, section of hematology/oncology; and director, genitourinary program, University of Chicago.

Dr. Walter M. Stadler picks the upcoming ASCO presentations he anticipates to be the most interesting in genitourinary research.

• 4501 A phase Ia study of MPDL3280A (anti-PDL1): Updated response and survival data in urothelial bladder cancer (UBC).

• 4502 Pembrolizumab (MK-3475) for advanced urothelial cancer: Updated results and biomarker analysis from KEYNOTE-012.

• 4505 A phase II/III, double-blind, randomized trial comparing maintenance lapatinib with placebo after first-line chemotherapy in HER1/2 positive metastatic bladder cancer patients.

• 4509 Identification of efficacy biomarkers in a large metastatic renal cell carcinoma (mRCC) cohort through next generation sequencing (NGS): Results from RECORD-3.

• 4516Expanded cohort results from CheckMate 016: A phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC).

• 5001Docetaxel and/or zoledronic acid for hormone-naive prostate cancer: First overall survival results from STAMPEDE (NCT00268476). The Oncology Report covered this study following a pre-meeting press conference.

• LBA5002A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521).

• 5000The Prostate Cancer Working Group 3 (PCWG3) consensus for trials in castration-resistant prostate cancer (CRPC).

• 5003Characterization of neuroendocrine prostate cancer (NEPC) in patients with metastatic castration resistant prostate cancer (mCRPC) resistant to abiraterone (Abi) or enzalutamide (Enz): Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).

• 5004Defining a molecular subclass of treatment resistant prostate cancer.

• 5007 TROG 03.06 and VCOG PR 01-03: The “timing of androgen deprivation therapy in prostate cancer patients with a rising PSA (TOAD)” collaborative randomized phase III trial.

Dr. Walter M. Stadler is the Fred C. Buffett Professor of Medicine and Surgery; associate dean for clinical research; chief, section of hematology/oncology; and director, genitourinary program, University of Chicago.

Nicotinamide, an inexpensive, over-the-counter form of vitamin B₃, is safe and efficacious for the chemoprevention of nonmelanoma skin cancer in patients at high risk, according to data from the Australian Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) Study.

Results reported in a press briefing held before the annual meeting of the American Society of Clinical Oncology showed that patients taking nicotinamide were about one-fourth less likely than peers taking a placebo to develop new basal cell and squamous cell skin cancers. They also had a smaller reduction in new actinic keratoses.

“Nicotinamide, vitamin B₃, significantly reduced nonmelanoma skin cancers and keratoses in just 12 months in a group of pretty high-risk patients. It’s safe, it’s almost obscenely inexpensive, and it’s already widely commercially available, so this one’s ready to go straight into the clinic,” commented senior investigator Dr. Diona Damian, professor of dermatology at the University of Sydney.

She cautioned that the results apply only to the population studied: adults who had experienced two or more nonmelanoma skin cancers in the past 5 years.

“These are the people we’d be recommending it for – people who have already got a skin cancer track record. It’s not something that we’d recommend at this stage for the general population,” she said. Likewise, the findings do not speak to patients at the other end of the spectrum who are in treatment for advanced or metastatic skin cancer, as they also were excluded.

That said, the researchers are planning additional studies in other populations, such patients who are at high risk because they have immunosuppression, according to Dr. Damian.

“We still need the overall skin cancer prevention strategies of sun-safe behavior, sunscreen, and regular skin surveillance,” she stressed, “but we now have an additional exciting opportunity for affordable skin cancer chemoprevention which we can instantly translate into clinical practice.”

Dr. Peter Paul Yu, ASCO President and a medical oncologist and hematologist who is director of cancer research at the Palo Alto Medical Foundation, Sunnyvale, Calif., commented, “This is a very exciting prevention trial. We all know that we clamor for preventing rather than treating diseases, and this is a major advance for us.”

Exposure to ultraviolet light packs a one-two punch to the skin, both damaging cellular DNA and suppressing the skin’s immune response, according to Dr. Damian. The investigators opted to test nicotinamide as it counters both of these events.

The 386 patients in ONTRAC had heavily sun damaged skin, with a mean of 8 nonmelanoma skin cancers in the past 5 years and 50 keratoses at baseline. They were randomized evenly to receive nicotinamide (500 mg twice daily) or placebo for 12 months.

Results showed that the average number of new nonmelanoma skin cancers per patient during the treatment period was 1.77 in the nicotinamide group and 2.42 in the placebo group. The difference translated to a 23% lower rate of new cancers with the vitamin.

“There were comparable reductions seen for both basal and squamous cell carcinomas,” Dr. Damian noted. “Interestingly, this reduction in skin cancers seemed to start as early as the first 3-month visit. And then when people stopped taking their tablets after 12 months, the benefit was no longer seen. In other words, you need to continue taking the tablets in order for them to be effective.”

The nicotinamide group also had a roughly 15% lower rate of new actinic keratoses, compared with the placebo group.

“Nicotinamide was very well tolerated. There was no difference in adverse events, blood parameters, or blood pressure in the two arms” of the study, reported Dr. Damian. She stressed that it is critically important to distinguish nicotinamide from niacin (nicotinic acid), another form of vitamin B₃ that has a host of side effects such as headache and flushing.

“One of the great things about [nicotinamide] is that it really has hardly any drug interactions, which means that elderly patients who may be taking a whole cocktail of medications for their heart disease and their hypertension, and whatever else, the nicotinamide won’t interact with those,” she added.

Some evidence also has shown nonsteroidal anti-inflammatory drugs to reduce the risk of skin cancer. “The advantage of nicotinamide is that it doesn’t have the potential gastrointestinal bleeding or renal side effects of nonsteroidals, so it may be suitable for a group of people who aren’t suitable for taking nonsteroidals,” she said. “In our ONTRAC study, we didn’t find synergy or additional benefit in people who were coincidentally taking nonsteroidals for other indications.”

The trial’s results should be generalizable to similar high-risk patients in less sunny parts of the world, Dr. Damian said. “If their skin has shown that degree of damage to get skin cancer, then we suspect nicotinamide would offer benefits to them as well.”

Dr. Damian disclosed no relevant conflicts of interest. The study was funded by the National Health & Medical Research Council.

Nicotinamide, an inexpensive, over-the-counter form of vitamin B₃, is safe and efficacious for the chemoprevention of nonmelanoma skin cancer in patients at high risk, according to data from the Australian Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) Study.

Results reported in a press briefing held before the annual meeting of the American Society of Clinical Oncology showed that patients taking nicotinamide were about one-fourth less likely than peers taking a placebo to develop new basal cell and squamous cell skin cancers. They also had a smaller reduction in new actinic keratoses.

“Nicotinamide, vitamin B₃, significantly reduced nonmelanoma skin cancers and keratoses in just 12 months in a group of pretty high-risk patients. It’s safe, it’s almost obscenely inexpensive, and it’s already widely commercially available, so this one’s ready to go straight into the clinic,” commented senior investigator Dr. Diona Damian, professor of dermatology at the University of Sydney.

She cautioned that the results apply only to the population studied: adults who had experienced two or more nonmelanoma skin cancers in the past 5 years.

“These are the people we’d be recommending it for – people who have already got a skin cancer track record. It’s not something that we’d recommend at this stage for the general population,” she said. Likewise, the findings do not speak to patients at the other end of the spectrum who are in treatment for advanced or metastatic skin cancer, as they also were excluded.

That said, the researchers are planning additional studies in other populations, such patients who are at high risk because they have immunosuppression, according to Dr. Damian.

“We still need the overall skin cancer prevention strategies of sun-safe behavior, sunscreen, and regular skin surveillance,” she stressed, “but we now have an additional exciting opportunity for affordable skin cancer chemoprevention which we can instantly translate into clinical practice.”

Dr. Peter Paul Yu, ASCO President and a medical oncologist and hematologist who is director of cancer research at the Palo Alto Medical Foundation, Sunnyvale, Calif., commented, “This is a very exciting prevention trial. We all know that we clamor for preventing rather than treating diseases, and this is a major advance for us.”

Exposure to ultraviolet light packs a one-two punch to the skin, both damaging cellular DNA and suppressing the skin’s immune response, according to Dr. Damian. The investigators opted to test nicotinamide as it counters both of these events.

The 386 patients in ONTRAC had heavily sun damaged skin, with a mean of 8 nonmelanoma skin cancers in the past 5 years and 50 keratoses at baseline. They were randomized evenly to receive nicotinamide (500 mg twice daily) or placebo for 12 months.

Results showed that the average number of new nonmelanoma skin cancers per patient during the treatment period was 1.77 in the nicotinamide group and 2.42 in the placebo group. The difference translated to a 23% lower rate of new cancers with the vitamin.

“There were comparable reductions seen for both basal and squamous cell carcinomas,” Dr. Damian noted. “Interestingly, this reduction in skin cancers seemed to start as early as the first 3-month visit. And then when people stopped taking their tablets after 12 months, the benefit was no longer seen. In other words, you need to continue taking the tablets in order for them to be effective.”

The nicotinamide group also had a roughly 15% lower rate of new actinic keratoses, compared with the placebo group.

“Nicotinamide was very well tolerated. There was no difference in adverse events, blood parameters, or blood pressure in the two arms” of the study, reported Dr. Damian. She stressed that it is critically important to distinguish nicotinamide from niacin (nicotinic acid), another form of vitamin B₃ that has a host of side effects such as headache and flushing.

“One of the great things about [nicotinamide] is that it really has hardly any drug interactions, which means that elderly patients who may be taking a whole cocktail of medications for their heart disease and their hypertension, and whatever else, the nicotinamide won’t interact with those,” she added.

Some evidence also has shown nonsteroidal anti-inflammatory drugs to reduce the risk of skin cancer. “The advantage of nicotinamide is that it doesn’t have the potential gastrointestinal bleeding or renal side effects of nonsteroidals, so it may be suitable for a group of people who aren’t suitable for taking nonsteroidals,” she said. “In our ONTRAC study, we didn’t find synergy or additional benefit in people who were coincidentally taking nonsteroidals for other indications.”

The trial’s results should be generalizable to similar high-risk patients in less sunny parts of the world, Dr. Damian said. “If their skin has shown that degree of damage to get skin cancer, then we suspect nicotinamide would offer benefits to them as well.”

Dr. Damian disclosed no relevant conflicts of interest. The study was funded by the National Health & Medical Research Council.

Nicotinamide, an inexpensive, over-the-counter form of vitamin B₃, is safe and efficacious for the chemoprevention of nonmelanoma skin cancer in patients at high risk, according to data from the Australian Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) Study.

Results reported in a press briefing held before the annual meeting of the American Society of Clinical Oncology showed that patients taking nicotinamide were about one-fourth less likely than peers taking a placebo to develop new basal cell and squamous cell skin cancers. They also had a smaller reduction in new actinic keratoses.

“Nicotinamide, vitamin B₃, significantly reduced nonmelanoma skin cancers and keratoses in just 12 months in a group of pretty high-risk patients. It’s safe, it’s almost obscenely inexpensive, and it’s already widely commercially available, so this one’s ready to go straight into the clinic,” commented senior investigator Dr. Diona Damian, professor of dermatology at the University of Sydney.

She cautioned that the results apply only to the population studied: adults who had experienced two or more nonmelanoma skin cancers in the past 5 years.

“These are the people we’d be recommending it for – people who have already got a skin cancer track record. It’s not something that we’d recommend at this stage for the general population,” she said. Likewise, the findings do not speak to patients at the other end of the spectrum who are in treatment for advanced or metastatic skin cancer, as they also were excluded.

That said, the researchers are planning additional studies in other populations, such patients who are at high risk because they have immunosuppression, according to Dr. Damian.

“We still need the overall skin cancer prevention strategies of sun-safe behavior, sunscreen, and regular skin surveillance,” she stressed, “but we now have an additional exciting opportunity for affordable skin cancer chemoprevention which we can instantly translate into clinical practice.”

Dr. Peter Paul Yu, ASCO President and a medical oncologist and hematologist who is director of cancer research at the Palo Alto Medical Foundation, Sunnyvale, Calif., commented, “This is a very exciting prevention trial. We all know that we clamor for preventing rather than treating diseases, and this is a major advance for us.”

Exposure to ultraviolet light packs a one-two punch to the skin, both damaging cellular DNA and suppressing the skin’s immune response, according to Dr. Damian. The investigators opted to test nicotinamide as it counters both of these events.

The 386 patients in ONTRAC had heavily sun damaged skin, with a mean of 8 nonmelanoma skin cancers in the past 5 years and 50 keratoses at baseline. They were randomized evenly to receive nicotinamide (500 mg twice daily) or placebo for 12 months.

Results showed that the average number of new nonmelanoma skin cancers per patient during the treatment period was 1.77 in the nicotinamide group and 2.42 in the placebo group. The difference translated to a 23% lower rate of new cancers with the vitamin.

“There were comparable reductions seen for both basal and squamous cell carcinomas,” Dr. Damian noted. “Interestingly, this reduction in skin cancers seemed to start as early as the first 3-month visit. And then when people stopped taking their tablets after 12 months, the benefit was no longer seen. In other words, you need to continue taking the tablets in order for them to be effective.”

The nicotinamide group also had a roughly 15% lower rate of new actinic keratoses, compared with the placebo group.

“Nicotinamide was very well tolerated. There was no difference in adverse events, blood parameters, or blood pressure in the two arms” of the study, reported Dr. Damian. She stressed that it is critically important to distinguish nicotinamide from niacin (nicotinic acid), another form of vitamin B₃ that has a host of side effects such as headache and flushing.

“One of the great things about [nicotinamide] is that it really has hardly any drug interactions, which means that elderly patients who may be taking a whole cocktail of medications for their heart disease and their hypertension, and whatever else, the nicotinamide won’t interact with those,” she added.

Some evidence also has shown nonsteroidal anti-inflammatory drugs to reduce the risk of skin cancer. “The advantage of nicotinamide is that it doesn’t have the potential gastrointestinal bleeding or renal side effects of nonsteroidals, so it may be suitable for a group of people who aren’t suitable for taking nonsteroidals,” she said. “In our ONTRAC study, we didn’t find synergy or additional benefit in people who were coincidentally taking nonsteroidals for other indications.”

The trial’s results should be generalizable to similar high-risk patients in less sunny parts of the world, Dr. Damian said. “If their skin has shown that degree of damage to get skin cancer, then we suspect nicotinamide would offer benefits to them as well.”

Dr. Damian disclosed no relevant conflicts of interest. The study was funded by the National Health & Medical Research Council.

Using chemotherapy earlier in the course of advanced prostate cancer improves outcomes, according to first survival results of the STAMPEDE trial (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy).

Results showed that adding docetaxel to the standard of hormone therapy at the time of diagnosis reduced the risk of treatment failure or death by 38% and the risk of death by 24%, researchers reported in a press briefing held in advance of the annual meeting of the American Society of Clinical Oncology. The benefit was clear among men with metastatic disease but less so among those with nonmetastatic disease.

roobcio/Thinkstock.com

“Docetaxel improves survival in men with hormone-naive prostate cancer starting hormone therapy for the first time,” concluded lead researcher Dr. Nicholas David James, director of the cancer research unit at the University of Warwick and consultant in clinical oncology at Queen Elizabeth Hospital Birmingham (England).

“Docetaxel should be considered as routine practice in men with newly diagnosed metastatic disease,” he asserted. “For nonmetastatic disease, there remains uncertainty as to whether there is a survival benefit or not, but it certainly improves failure-free survival by a substantial amount, so we would argue that it should be considered for selected men with high-risk nonmetastatic disease.”

Clinicians should use an individualized approach to adding docetaxel in the subgroup with nonmetastatic disease. “What I am doing in my own clinic, for example, is having a discussion with the patients about the pros and cons. … I think it will be something we discuss on a case-by-case basis,” he said, adding that a planned meta-analysis should better clarify the survival benefit in this subgroup.

Dr. Peter Paul Yu, ASCO president and a medical oncologist and hematologist, who is director of cancer research at the Palo Alto Medical Foundation, Sunnyvale, Calif., said that the STAMPEDE data contribute to an ongoing paradigm shift in treating advanced prostate cancer.

“The paradigm for years or even decades has been to treat this with hormone therapy because [it] is relatively less toxic. … The advice has been to use hormone therapy until it’s exhausted, until there is no response left, and then at the last moment use chemotherapy, which often is a potentially self-defeating strategy because you are using chemotherapy when the disease has evolved to a point where it’s much more aggressive,” he said.

Accumulating data, however, suggest that a strategy of combining chemotherapy with hormonal therapy upfront yields better outcomes than their sequential use. “This paradigm shift is continuing and should be highlighted,” he maintained.

“The really interesting thing is the hint … and I would say a very strong hint as an editorial comment, that this strategy of bringing chemotherapy early on can have a benefit even in men who do not have evidence of metastases at the time they are starting hormone therapy … what we would traditionally call the adjuvant use of chemotherapy,” Dr. Yu added.

Men were eligible for STAMPEDE if they were starting long-term hormone therapy for the first time and had high-risk locally advanced disease, lymph node–positive disease, metastatic disease, or disease that had relapsed aggressively after surgery or radiation therapy. STAMPEDE has an innovative, adaptive design whereby novel agents can be incrementally added to those found to be efficacious in earlier arms, generating a new standard of care. The trial receives funding and support in part from Sanofi-Aventis, Novartis, Pfizer, Janssen, and Astellas.

Dr. James presented findings for four of the trial’s nine arms, in which 2,962 patients were randomized to standard of care (androgen deprivation therapy with or without radiation therapy) alone, or with the addition of six cycles of docetaxel (Taxotere), 2 years of the bisphosphonate zoledronic acid (Zometa), or both.

Docetaxel is approved by the U.S. Food and Drug Administration for treatment of metastatic hormone-refractory prostate cancer, and zoledronic acid is approved for the treatment of hypercalcemia due to cancer.

With a median follow-up of 42 months, compared with standard care alone, adding docetaxel significantly reduced the risks of failure-free survival events (hazard ratio, 0.62) and death (HR, 0.76). Median overall survival was 77 months with the drug and 67 months without it, and the difference was largely driven by prostate cancer deaths, according to Dr. James.

About 60% of the men had metastases. In stratified analyses, adding docetaxel improved failure-free survival whether men had metastatic disease or not, but it improved overall survival only in those with metastatic disease (43 vs. 65 months). However, the standard-care arm in the nonmetastatic subgroup performed better than expected, and there have been too few deaths in that subgroup overall to fully power the analysis, Dr. James said.

Toxicity with the addition of docetaxel was manageable. Zoledronic acid did not improve either outcome relative to hormone therapy alone, and adding both zoledronic acid and docetaxel netted similar results to those seen with docetaxel alone.

Several other therapies, including next-generation hormone therapies and chemotherapy agents, also are showing promise in prostate cancer, and the optimal timing and sequencing of agents is unknown. STAMPEDE is the first to look at docetaxel and these hormone therapies at the time of diagnosis of advanced disease, he noted.

At present, the data support giving docetaxel before either abiraterone or enzalutamide in this treatment setting, as the drug’s survival advantage persisted even though patients often went on to receive those hormone therapies; however, that strategy might change with future results from this and other trials. “To be honest, it would be a nice position to be in if we had two treatments that improved overall survival upfront. That just gives us a choice. It would be good news obviously,” he concluded.

Dr. James disclosed that he has a consulting, advisory, or speakers’ bureau role with or receives honoraria or research funding (institutional) from Sanofi, Bayer, Merck, Astellas, Janssen, Pierre Fabre, Ferring, OncoGenex, and Pfizer.

Using chemotherapy earlier in the course of advanced prostate cancer improves outcomes, according to first survival results of the STAMPEDE trial (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy).

Results showed that adding docetaxel to the standard of hormone therapy at the time of diagnosis reduced the risk of treatment failure or death by 38% and the risk of death by 24%, researchers reported in a press briefing held in advance of the annual meeting of the American Society of Clinical Oncology. The benefit was clear among men with metastatic disease but less so among those with nonmetastatic disease.

roobcio/Thinkstock.com

“Docetaxel improves survival in men with hormone-naive prostate cancer starting hormone therapy for the first time,” concluded lead researcher Dr. Nicholas David James, director of the cancer research unit at the University of Warwick and consultant in clinical oncology at Queen Elizabeth Hospital Birmingham (England).

“Docetaxel should be considered as routine practice in men with newly diagnosed metastatic disease,” he asserted. “For nonmetastatic disease, there remains uncertainty as to whether there is a survival benefit or not, but it certainly improves failure-free survival by a substantial amount, so we would argue that it should be considered for selected men with high-risk nonmetastatic disease.”

Clinicians should use an individualized approach to adding docetaxel in the subgroup with nonmetastatic disease. “What I am doing in my own clinic, for example, is having a discussion with the patients about the pros and cons. … I think it will be something we discuss on a case-by-case basis,” he said, adding that a planned meta-analysis should better clarify the survival benefit in this subgroup.

Dr. Peter Paul Yu, ASCO president and a medical oncologist and hematologist, who is director of cancer research at the Palo Alto Medical Foundation, Sunnyvale, Calif., said that the STAMPEDE data contribute to an ongoing paradigm shift in treating advanced prostate cancer.

“The paradigm for years or even decades has been to treat this with hormone therapy because [it] is relatively less toxic. … The advice has been to use hormone therapy until it’s exhausted, until there is no response left, and then at the last moment use chemotherapy, which often is a potentially self-defeating strategy because you are using chemotherapy when the disease has evolved to a point where it’s much more aggressive,” he said.

Accumulating data, however, suggest that a strategy of combining chemotherapy with hormonal therapy upfront yields better outcomes than their sequential use. “This paradigm shift is continuing and should be highlighted,” he maintained.

“The really interesting thing is the hint … and I would say a very strong hint as an editorial comment, that this strategy of bringing chemotherapy early on can have a benefit even in men who do not have evidence of metastases at the time they are starting hormone therapy … what we would traditionally call the adjuvant use of chemotherapy,” Dr. Yu added.

Men were eligible for STAMPEDE if they were starting long-term hormone therapy for the first time and had high-risk locally advanced disease, lymph node–positive disease, metastatic disease, or disease that had relapsed aggressively after surgery or radiation therapy. STAMPEDE has an innovative, adaptive design whereby novel agents can be incrementally added to those found to be efficacious in earlier arms, generating a new standard of care. The trial receives funding and support in part from Sanofi-Aventis, Novartis, Pfizer, Janssen, and Astellas.

Dr. James presented findings for four of the trial’s nine arms, in which 2,962 patients were randomized to standard of care (androgen deprivation therapy with or without radiation therapy) alone, or with the addition of six cycles of docetaxel (Taxotere), 2 years of the bisphosphonate zoledronic acid (Zometa), or both.

Docetaxel is approved by the U.S. Food and Drug Administration for treatment of metastatic hormone-refractory prostate cancer, and zoledronic acid is approved for the treatment of hypercalcemia due to cancer.

With a median follow-up of 42 months, compared with standard care alone, adding docetaxel significantly reduced the risks of failure-free survival events (hazard ratio, 0.62) and death (HR, 0.76). Median overall survival was 77 months with the drug and 67 months without it, and the difference was largely driven by prostate cancer deaths, according to Dr. James.

About 60% of the men had metastases. In stratified analyses, adding docetaxel improved failure-free survival whether men had metastatic disease or not, but it improved overall survival only in those with metastatic disease (43 vs. 65 months). However, the standard-care arm in the nonmetastatic subgroup performed better than expected, and there have been too few deaths in that subgroup overall to fully power the analysis, Dr. James said.

Toxicity with the addition of docetaxel was manageable. Zoledronic acid did not improve either outcome relative to hormone therapy alone, and adding both zoledronic acid and docetaxel netted similar results to those seen with docetaxel alone.

Several other therapies, including next-generation hormone therapies and chemotherapy agents, also are showing promise in prostate cancer, and the optimal timing and sequencing of agents is unknown. STAMPEDE is the first to look at docetaxel and these hormone therapies at the time of diagnosis of advanced disease, he noted.

At present, the data support giving docetaxel before either abiraterone or enzalutamide in this treatment setting, as the drug’s survival advantage persisted even though patients often went on to receive those hormone therapies; however, that strategy might change with future results from this and other trials. “To be honest, it would be a nice position to be in if we had two treatments that improved overall survival upfront. That just gives us a choice. It would be good news obviously,” he concluded.

Dr. James disclosed that he has a consulting, advisory, or speakers’ bureau role with or receives honoraria or research funding (institutional) from Sanofi, Bayer, Merck, Astellas, Janssen, Pierre Fabre, Ferring, OncoGenex, and Pfizer.

Using chemotherapy earlier in the course of advanced prostate cancer improves outcomes, according to first survival results of the STAMPEDE trial (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy).

Results showed that adding docetaxel to the standard of hormone therapy at the time of diagnosis reduced the risk of treatment failure or death by 38% and the risk of death by 24%, researchers reported in a press briefing held in advance of the annual meeting of the American Society of Clinical Oncology. The benefit was clear among men with metastatic disease but less so among those with nonmetastatic disease.

roobcio/Thinkstock.com

“Docetaxel improves survival in men with hormone-naive prostate cancer starting hormone therapy for the first time,” concluded lead researcher Dr. Nicholas David James, director of the cancer research unit at the University of Warwick and consultant in clinical oncology at Queen Elizabeth Hospital Birmingham (England).

“Docetaxel should be considered as routine practice in men with newly diagnosed metastatic disease,” he asserted. “For nonmetastatic disease, there remains uncertainty as to whether there is a survival benefit or not, but it certainly improves failure-free survival by a substantial amount, so we would argue that it should be considered for selected men with high-risk nonmetastatic disease.”

Clinicians should use an individualized approach to adding docetaxel in the subgroup with nonmetastatic disease. “What I am doing in my own clinic, for example, is having a discussion with the patients about the pros and cons. … I think it will be something we discuss on a case-by-case basis,” he said, adding that a planned meta-analysis should better clarify the survival benefit in this subgroup.

Dr. Peter Paul Yu, ASCO president and a medical oncologist and hematologist, who is director of cancer research at the Palo Alto Medical Foundation, Sunnyvale, Calif., said that the STAMPEDE data contribute to an ongoing paradigm shift in treating advanced prostate cancer.

“The paradigm for years or even decades has been to treat this with hormone therapy because [it] is relatively less toxic. … The advice has been to use hormone therapy until it’s exhausted, until there is no response left, and then at the last moment use chemotherapy, which often is a potentially self-defeating strategy because you are using chemotherapy when the disease has evolved to a point where it’s much more aggressive,” he said.

Accumulating data, however, suggest that a strategy of combining chemotherapy with hormonal therapy upfront yields better outcomes than their sequential use. “This paradigm shift is continuing and should be highlighted,” he maintained.

“The really interesting thing is the hint … and I would say a very strong hint as an editorial comment, that this strategy of bringing chemotherapy early on can have a benefit even in men who do not have evidence of metastases at the time they are starting hormone therapy … what we would traditionally call the adjuvant use of chemotherapy,” Dr. Yu added.

Men were eligible for STAMPEDE if they were starting long-term hormone therapy for the first time and had high-risk locally advanced disease, lymph node–positive disease, metastatic disease, or disease that had relapsed aggressively after surgery or radiation therapy. STAMPEDE has an innovative, adaptive design whereby novel agents can be incrementally added to those found to be efficacious in earlier arms, generating a new standard of care. The trial receives funding and support in part from Sanofi-Aventis, Novartis, Pfizer, Janssen, and Astellas.

Dr. James presented findings for four of the trial’s nine arms, in which 2,962 patients were randomized to standard of care (androgen deprivation therapy with or without radiation therapy) alone, or with the addition of six cycles of docetaxel (Taxotere), 2 years of the bisphosphonate zoledronic acid (Zometa), or both.

Docetaxel is approved by the U.S. Food and Drug Administration for treatment of metastatic hormone-refractory prostate cancer, and zoledronic acid is approved for the treatment of hypercalcemia due to cancer.

With a median follow-up of 42 months, compared with standard care alone, adding docetaxel significantly reduced the risks of failure-free survival events (hazard ratio, 0.62) and death (HR, 0.76). Median overall survival was 77 months with the drug and 67 months without it, and the difference was largely driven by prostate cancer deaths, according to Dr. James.

About 60% of the men had metastases. In stratified analyses, adding docetaxel improved failure-free survival whether men had metastatic disease or not, but it improved overall survival only in those with metastatic disease (43 vs. 65 months). However, the standard-care arm in the nonmetastatic subgroup performed better than expected, and there have been too few deaths in that subgroup overall to fully power the analysis, Dr. James said.

Toxicity with the addition of docetaxel was manageable. Zoledronic acid did not improve either outcome relative to hormone therapy alone, and adding both zoledronic acid and docetaxel netted similar results to those seen with docetaxel alone.

Several other therapies, including next-generation hormone therapies and chemotherapy agents, also are showing promise in prostate cancer, and the optimal timing and sequencing of agents is unknown. STAMPEDE is the first to look at docetaxel and these hormone therapies at the time of diagnosis of advanced disease, he noted.

At present, the data support giving docetaxel before either abiraterone or enzalutamide in this treatment setting, as the drug’s survival advantage persisted even though patients often went on to receive those hormone therapies; however, that strategy might change with future results from this and other trials. “To be honest, it would be a nice position to be in if we had two treatments that improved overall survival upfront. That just gives us a choice. It would be good news obviously,” he concluded.

Dr. James disclosed that he has a consulting, advisory, or speakers’ bureau role with or receives honoraria or research funding (institutional) from Sanofi, Bayer, Merck, Astellas, Janssen, Pierre Fabre, Ferring, OncoGenex, and Pfizer.

Augmenting standard chemotherapy regimens with additional cytotoxic agents significantly boosted event-free survival rates in children with high-risk forms of Wilms tumor, particularly those with advanced-stage disease.

Adding doxorubicin to standard therapy with vincristine and dactinomycin in patients with stage I/II Wilms tumors carrying high-risk loss of heterozygosity mutations increased 4-year event-free survival (EFS) rates from 74.9% (with vincristine and dactinomycin chemotherapy alone), to 83.9.%

In patients with high-risk stage III/IV disease, adding four cycles of cyclophosphamide and etoposide to a standard regimen of vincristine, dactinomycin, doxorubicin and radiation improved 4-year EFS from 65.9% to 91.5%, reported Dr. David B. Dix of the British Columbia Children’s Hospital, Vancouver, B.C.

“Our committee is particularly encouraged by these results in that they clearly show evidence that augmentation of therapy can overcome a known adverse biomarker, and they also provide encouragement to search for other biomarkers of prognostic significance, ideally found in a higher percentage of patients,” he said at a briefing of studies to be presented at the 2015 annual meeting of the American Society of Clinical Oncology.

Dr. Julie M. Vose, ASCO president-elect, who comoderated the briefing but was not involved in the studies, said that the results show the importance of genetic testing to prevent overtreatment and rein in costs for low-risk patients, and to help improve treatment of high-risk patients with augmented therapies or additional treatment strategies.

The investigators focused on improving outcomes for children with favorable histology Wilms tumor who have loss of heterozygosity (LOH) mutations in chromosomal location 1p and 16q.

In the National Wilms Tumor Study 5, a multicenter North American cooperative trial, children with these mutations, who comprised 5% of the study population, had significantly worse outcomes. Among patients with stage I/II disease with LOH mutations at both chromosomal locations, the 4-year EFS in that trial was 74.9%, compared with 92% for patients with no LOH mutations. Among patients with stage III/IV disease, the respective 4-year EFS rates were 65.9% vs. 83%.

The investigators tested whether augmenting therapy would improve EFS for patients with favorable histology Wilms tumor with the combined LOH 1p and 16q mutations in two trials:

AREN0532 compared vincristine and dactinomycin with the same two drugs plus doxorubicin in patients with stage I/II disease.

AREN0533compared vincristine, dactinomycin, doxorubicin and radiation therapy with the same regimen plus four cycles of cyclophosphamide and etoposide in patients with stage III/IV disease.

In each trial, 4-year EFS rates were compared with those of the National Wilms Tumor Study 4. Median follow-up was 3.6 years.

The patients were generally able to tolerate the therapy well, Dr. Dix said. Short-term toxicities for patients with stage I/II disease were manageable, he noted.

Among patients with stage III/IV disease, the augmented regimen was associated with myelosuppression in 60% of patients, although this too was manageable, the investigators reported.

Dr. Dix and his colleagues noted that the augmented regimen for stage III/IV tumors may spare many patients from requiring even more intensive salvage therapy. They also acknowledged, however, that the augmented regimen is likely to cause reduced fertility in some patients, and urged clinicians to discuss the risks and benefits of augmented therapy with the patients’ families.

Testing for LOH 1p and 16q is available at the Children’s Oncology Group Biopathology Center at Nationwide Children’s Hospital in Columbus, Ohio, and at several other centers across North America, Dr. Dix noted.

Augmenting standard chemotherapy regimens with additional cytotoxic agents significantly boosted event-free survival rates in children with high-risk forms of Wilms tumor, particularly those with advanced-stage disease.

Adding doxorubicin to standard therapy with vincristine and dactinomycin in patients with stage I/II Wilms tumors carrying high-risk loss of heterozygosity mutations increased 4-year event-free survival (EFS) rates from 74.9% (with vincristine and dactinomycin chemotherapy alone), to 83.9.%

In patients with high-risk stage III/IV disease, adding four cycles of cyclophosphamide and etoposide to a standard regimen of vincristine, dactinomycin, doxorubicin and radiation improved 4-year EFS from 65.9% to 91.5%, reported Dr. David B. Dix of the British Columbia Children’s Hospital, Vancouver, B.C.

“Our committee is particularly encouraged by these results in that they clearly show evidence that augmentation of therapy can overcome a known adverse biomarker, and they also provide encouragement to search for other biomarkers of prognostic significance, ideally found in a higher percentage of patients,” he said at a briefing of studies to be presented at the 2015 annual meeting of the American Society of Clinical Oncology.

Dr. Julie M. Vose, ASCO president-elect, who comoderated the briefing but was not involved in the studies, said that the results show the importance of genetic testing to prevent overtreatment and rein in costs for low-risk patients, and to help improve treatment of high-risk patients with augmented therapies or additional treatment strategies.

The investigators focused on improving outcomes for children with favorable histology Wilms tumor who have loss of heterozygosity (LOH) mutations in chromosomal location 1p and 16q.

In the National Wilms Tumor Study 5, a multicenter North American cooperative trial, children with these mutations, who comprised 5% of the study population, had significantly worse outcomes. Among patients with stage I/II disease with LOH mutations at both chromosomal locations, the 4-year EFS in that trial was 74.9%, compared with 92% for patients with no LOH mutations. Among patients with stage III/IV disease, the respective 4-year EFS rates were 65.9% vs. 83%.

The investigators tested whether augmenting therapy would improve EFS for patients with favorable histology Wilms tumor with the combined LOH 1p and 16q mutations in two trials:

AREN0532 compared vincristine and dactinomycin with the same two drugs plus doxorubicin in patients with stage I/II disease.

AREN0533compared vincristine, dactinomycin, doxorubicin and radiation therapy with the same regimen plus four cycles of cyclophosphamide and etoposide in patients with stage III/IV disease.

In each trial, 4-year EFS rates were compared with those of the National Wilms Tumor Study 4. Median follow-up was 3.6 years.

The patients were generally able to tolerate the therapy well, Dr. Dix said. Short-term toxicities for patients with stage I/II disease were manageable, he noted.

Among patients with stage III/IV disease, the augmented regimen was associated with myelosuppression in 60% of patients, although this too was manageable, the investigators reported.

Dr. Dix and his colleagues noted that the augmented regimen for stage III/IV tumors may spare many patients from requiring even more intensive salvage therapy. They also acknowledged, however, that the augmented regimen is likely to cause reduced fertility in some patients, and urged clinicians to discuss the risks and benefits of augmented therapy with the patients’ families.

Testing for LOH 1p and 16q is available at the Children’s Oncology Group Biopathology Center at Nationwide Children’s Hospital in Columbus, Ohio, and at several other centers across North America, Dr. Dix noted.

Augmenting standard chemotherapy regimens with additional cytotoxic agents significantly boosted event-free survival rates in children with high-risk forms of Wilms tumor, particularly those with advanced-stage disease.

Adding doxorubicin to standard therapy with vincristine and dactinomycin in patients with stage I/II Wilms tumors carrying high-risk loss of heterozygosity mutations increased 4-year event-free survival (EFS) rates from 74.9% (with vincristine and dactinomycin chemotherapy alone), to 83.9.%

In patients with high-risk stage III/IV disease, adding four cycles of cyclophosphamide and etoposide to a standard regimen of vincristine, dactinomycin, doxorubicin and radiation improved 4-year EFS from 65.9% to 91.5%, reported Dr. David B. Dix of the British Columbia Children’s Hospital, Vancouver, B.C.

“Our committee is particularly encouraged by these results in that they clearly show evidence that augmentation of therapy can overcome a known adverse biomarker, and they also provide encouragement to search for other biomarkers of prognostic significance, ideally found in a higher percentage of patients,” he said at a briefing of studies to be presented at the 2015 annual meeting of the American Society of Clinical Oncology.

Dr. Julie M. Vose, ASCO president-elect, who comoderated the briefing but was not involved in the studies, said that the results show the importance of genetic testing to prevent overtreatment and rein in costs for low-risk patients, and to help improve treatment of high-risk patients with augmented therapies or additional treatment strategies.

The investigators focused on improving outcomes for children with favorable histology Wilms tumor who have loss of heterozygosity (LOH) mutations in chromosomal location 1p and 16q.

In the National Wilms Tumor Study 5, a multicenter North American cooperative trial, children with these mutations, who comprised 5% of the study population, had significantly worse outcomes. Among patients with stage I/II disease with LOH mutations at both chromosomal locations, the 4-year EFS in that trial was 74.9%, compared with 92% for patients with no LOH mutations. Among patients with stage III/IV disease, the respective 4-year EFS rates were 65.9% vs. 83%.

The investigators tested whether augmenting therapy would improve EFS for patients with favorable histology Wilms tumor with the combined LOH 1p and 16q mutations in two trials:

AREN0532 compared vincristine and dactinomycin with the same two drugs plus doxorubicin in patients with stage I/II disease.

AREN0533compared vincristine, dactinomycin, doxorubicin and radiation therapy with the same regimen plus four cycles of cyclophosphamide and etoposide in patients with stage III/IV disease.

In each trial, 4-year EFS rates were compared with those of the National Wilms Tumor Study 4. Median follow-up was 3.6 years.

The patients were generally able to tolerate the therapy well, Dr. Dix said. Short-term toxicities for patients with stage I/II disease were manageable, he noted.

Among patients with stage III/IV disease, the augmented regimen was associated with myelosuppression in 60% of patients, although this too was manageable, the investigators reported.

Dr. Dix and his colleagues noted that the augmented regimen for stage III/IV tumors may spare many patients from requiring even more intensive salvage therapy. They also acknowledged, however, that the augmented regimen is likely to cause reduced fertility in some patients, and urged clinicians to discuss the risks and benefits of augmented therapy with the patients’ families.

Testing for LOH 1p and 16q is available at the Children’s Oncology Group Biopathology Center at Nationwide Children’s Hospital in Columbus, Ohio, and at several other centers across North America, Dr. Dix noted.

Adding the investigational monoclonal antibody elotuzumab to a standard regimen for early relapsed/refractory multiple myeloma extended the duration of remissions by a mean of 5 months.

The combination of elotuzumab (elo), lenalidomide (len), and dexamethasone (dex) was associated with a 30% reduction in the risk of disease progression or death compared with len/dex alone, and the benefit of the drug was also seen, although to a lesser degree, in patients with high-risk disease mutations, reported Dr. Sagar Lonial of the Winship Cancer Institute of Emory University, Atlanta.

“We were certainly excited about the fact that there is such a big difference in progression-free survival between the two arms,” he said at a briefing on studies to be presented at the annual meeting of the American Society of Clinical Oncology.

“Patients who received elotuzumab had a longer duration of remission and had a higher overall response rate, and this improvement in clinical parameters occurred without a significant increase in adverse events or toxicity,” he added.

Dr. Julie M. Vose, ASCO president-elect, who comoderated the briefing, said that “although we have had monoclonal antibodies in a number of other malignancies for years, this truly is the first one for myeloma.”

Dr. Lonial reported interim results from ELOQUENT-2, a phase III study comparing the efficacy and safety of the elo/len/dex combination vs. len/dex alone in 646 patients with relapsed/refractory multiple myeloma who had received one, two, or three prior lines of therapy and whose disease was not resistant to len/dex.

The patients were randomized to receive either oral len/dex on a standard schedule, or oral lenalidomide plus oral dexamethasone on weeks when there was no elotuzumab infusion, with both oral and intravenous dexamethasone delivered on weeks when the antibody was delivered by solutional infusion. The regimens were delivered in 28-day cycles until disease progression or unacceptable toxicities occurred.

At 24 months median follow-up, the mean progression-free survival (PFS) for patients on elo/len/dex was 19.4 months, compared with 14.9 months for len/dex alone (P = .0004). One-year PFS rates were 68% for elo/len/dex, compared with 57% for len/dex. Two-year PFS rates were 41% vs. 27%, respectively.

The overall response rate with the antibody-containing combination was 79% compared with 66% for len/dex alone (P = .0002). Dr. Lonial noted that the antibody-containing combination was effective both in patients with average risk, and in those with the high risk cytogenetic abnormalities, including the 17p deletion and the t(4;14) chromosomal translocation, although the response was not as robust in these patients.

A total of 210 patients died during follow-up, 94 who had been treated with elo/len/dex, and 116 who had been treated with len/dex.

Grade 3 or 4 adverse events occurring in 15% or more of patients included neutropenia in 25% of patients on elo/len/dex, and 33% of patients on len/dex, and anemia, which occurred in 15% and 16% of patients, respectively. In all, 10% of patients in the elotuzumab arm had mild infusion reactions after the first few doses.

Based on data from earlier trials, the Food and Drug Administration has granted elotuzumab breakthrough designation for treatment of multiple myeloma that has relapsed or is refractory to at least one prior line of therapy. Breakthrough status entitles the manufacturer to an expedited review of the drug.

Adding the investigational monoclonal antibody elotuzumab to a standard regimen for early relapsed/refractory multiple myeloma extended the duration of remissions by a mean of 5 months.

The combination of elotuzumab (elo), lenalidomide (len), and dexamethasone (dex) was associated with a 30% reduction in the risk of disease progression or death compared with len/dex alone, and the benefit of the drug was also seen, although to a lesser degree, in patients with high-risk disease mutations, reported Dr. Sagar Lonial of the Winship Cancer Institute of Emory University, Atlanta.

“We were certainly excited about the fact that there is such a big difference in progression-free survival between the two arms,” he said at a briefing on studies to be presented at the annual meeting of the American Society of Clinical Oncology.

“Patients who received elotuzumab had a longer duration of remission and had a higher overall response rate, and this improvement in clinical parameters occurred without a significant increase in adverse events or toxicity,” he added.

Dr. Julie M. Vose, ASCO president-elect, who comoderated the briefing, said that “although we have had monoclonal antibodies in a number of other malignancies for years, this truly is the first one for myeloma.”

Dr. Lonial reported interim results from ELOQUENT-2, a phase III study comparing the efficacy and safety of the elo/len/dex combination vs. len/dex alone in 646 patients with relapsed/refractory multiple myeloma who had received one, two, or three prior lines of therapy and whose disease was not resistant to len/dex.

The patients were randomized to receive either oral len/dex on a standard schedule, or oral lenalidomide plus oral dexamethasone on weeks when there was no elotuzumab infusion, with both oral and intravenous dexamethasone delivered on weeks when the antibody was delivered by solutional infusion. The regimens were delivered in 28-day cycles until disease progression or unacceptable toxicities occurred.

At 24 months median follow-up, the mean progression-free survival (PFS) for patients on elo/len/dex was 19.4 months, compared with 14.9 months for len/dex alone (P = .0004). One-year PFS rates were 68% for elo/len/dex, compared with 57% for len/dex. Two-year PFS rates were 41% vs. 27%, respectively.

The overall response rate with the antibody-containing combination was 79% compared with 66% for len/dex alone (P = .0002). Dr. Lonial noted that the antibody-containing combination was effective both in patients with average risk, and in those with the high risk cytogenetic abnormalities, including the 17p deletion and the t(4;14) chromosomal translocation, although the response was not as robust in these patients.

A total of 210 patients died during follow-up, 94 who had been treated with elo/len/dex, and 116 who had been treated with len/dex.

Grade 3 or 4 adverse events occurring in 15% or more of patients included neutropenia in 25% of patients on elo/len/dex, and 33% of patients on len/dex, and anemia, which occurred in 15% and 16% of patients, respectively. In all, 10% of patients in the elotuzumab arm had mild infusion reactions after the first few doses.

Based on data from earlier trials, the Food and Drug Administration has granted elotuzumab breakthrough designation for treatment of multiple myeloma that has relapsed or is refractory to at least one prior line of therapy. Breakthrough status entitles the manufacturer to an expedited review of the drug.

Adding the investigational monoclonal antibody elotuzumab to a standard regimen for early relapsed/refractory multiple myeloma extended the duration of remissions by a mean of 5 months.

The combination of elotuzumab (elo), lenalidomide (len), and dexamethasone (dex) was associated with a 30% reduction in the risk of disease progression or death compared with len/dex alone, and the benefit of the drug was also seen, although to a lesser degree, in patients with high-risk disease mutations, reported Dr. Sagar Lonial of the Winship Cancer Institute of Emory University, Atlanta.

“We were certainly excited about the fact that there is such a big difference in progression-free survival between the two arms,” he said at a briefing on studies to be presented at the annual meeting of the American Society of Clinical Oncology.

“Patients who received elotuzumab had a longer duration of remission and had a higher overall response rate, and this improvement in clinical parameters occurred without a significant increase in adverse events or toxicity,” he added.

Dr. Julie M. Vose, ASCO president-elect, who comoderated the briefing, said that “although we have had monoclonal antibodies in a number of other malignancies for years, this truly is the first one for myeloma.”

Dr. Lonial reported interim results from ELOQUENT-2, a phase III study comparing the efficacy and safety of the elo/len/dex combination vs. len/dex alone in 646 patients with relapsed/refractory multiple myeloma who had received one, two, or three prior lines of therapy and whose disease was not resistant to len/dex.

The patients were randomized to receive either oral len/dex on a standard schedule, or oral lenalidomide plus oral dexamethasone on weeks when there was no elotuzumab infusion, with both oral and intravenous dexamethasone delivered on weeks when the antibody was delivered by solutional infusion. The regimens were delivered in 28-day cycles until disease progression or unacceptable toxicities occurred.

At 24 months median follow-up, the mean progression-free survival (PFS) for patients on elo/len/dex was 19.4 months, compared with 14.9 months for len/dex alone (P = .0004). One-year PFS rates were 68% for elo/len/dex, compared with 57% for len/dex. Two-year PFS rates were 41% vs. 27%, respectively.

The overall response rate with the antibody-containing combination was 79% compared with 66% for len/dex alone (P = .0002). Dr. Lonial noted that the antibody-containing combination was effective both in patients with average risk, and in those with the high risk cytogenetic abnormalities, including the 17p deletion and the t(4;14) chromosomal translocation, although the response was not as robust in these patients.

A total of 210 patients died during follow-up, 94 who had been treated with elo/len/dex, and 116 who had been treated with len/dex.

Grade 3 or 4 adverse events occurring in 15% or more of patients included neutropenia in 25% of patients on elo/len/dex, and 33% of patients on len/dex, and anemia, which occurred in 15% and 16% of patients, respectively. In all, 10% of patients in the elotuzumab arm had mild infusion reactions after the first few doses.

Based on data from earlier trials, the Food and Drug Administration has granted elotuzumab breakthrough designation for treatment of multiple myeloma that has relapsed or is refractory to at least one prior line of therapy. Breakthrough status entitles the manufacturer to an expedited review of the drug.

Measured levels of cardiorespiratory fitness appear to be as predictive of cancer risk and survival as they are of heart disease risk and survival, according to a 20-year, prospective study of more than 17,000 men.

The risks of lung and colorectal cancer were reduced 68% and 38%, respectively, in men with the highest level of cardiorespiratory fitness, compared with those who were the least fit.

Cardiorespiratory fitness did not significantly reduce prostate cancer risk, but the risk of dying was significantly lower among men with prostate, lung, or colorectal cancer if they were more fit in middle age (P less than .001).

Prior studies have shown that being physically active is protective against cancer, but this study is unique because it looked at a very specific marker – cardiorespiratory fitness as measured by maximal exercise tolerance testing, Dr. Susan G. Lakoski said during a press briefing highlighting research to be presented at the upcoming American Society of Clinical Oncology (ASCO) meeting.

"Fitness as formal measurement is known to prevent cardiovascular disease and it’s also known that it helps in terms of survival risk, but what hasn’t been known is does it prevent incident cancer and mortality after cancer diagnosis and that’s what’s elucidated in the current study," said Dr. Lakoski, director of the cardiovascular prevention program for cancer patients at the University of Vermont, Burlington.

She noted that several organizations, including the President’s Council on Fitness, Sports & Nutrition, are trying to measure fitness formally and that the American Heart Association has issued policy statements that fitness should be measured and normative values developed to determine cardiovascular risk.

"Fitness is a formal measurement; it’s sort of like measuring your LDL cholesterol, you get a very specific number to target," Dr. Lakoski said. "When you ask someone about their physical activity, you don’t get that information."

The 17,049 men in the study underwent exercise tolerance testing with a treadmill or bicycle and risk factor assessment at an average age of 50 years as part of the Cooper Center Longitudinal Study in Dallas. Metabolic equivalents (METs) were used to record the men’s cardiorespiratory fitness (CRF) and to place them into five CRF quintiles. Lung, colorectal and prostate cancers were assessed using Medicare claims data at Medicare age, and cause-specific mortality was determined after cancer diagnosis.

Over the 20 years of follow-up, 2,885 men were diagnosed with prostate, lung, or colorectal cancer and 769 died.

Compared with men in the lowest CRF quintile, hazard ratios (HR) for incident lung, colorectal and prostate cancer among men in the highest quintile were 0.32 (P less than .001), 0.62 (P = .05) and 1.13 (P = .14), after researchers adjusted for such risk factors as smoking, body mass index, and age, Dr. Lakoski reported.

In men who developed cancer, both cancer-specific mortality and cardiovascular-specific mortality declined across increasing CRF quintiles (P values less than .0001).

Even a single MET increase reduced the risk of dying from cancer and cardiovascular disease by 14% and 23%, respectively (HR, 0.86; HR, 0.77; P less than .001 for both measures), Dr. Lakoski said.

Another striking finding is that even if men aren’t obese, they still have an increased risk of cancer if they aren’t fit, "which suggests that everyone can benefit from improving their fitness," Dr. Sandra Swain, ASCO president and medical director of the Washington (D.C.) Cancer Institute told reporters.

"The findings make clear that patients should be advised that they need to achieve a certain fitness level, and not just be told that they need to exercise," Dr. Swain noted in a statement.

"A primary care physician should start to think about fitness in the same light as body weight or high cholesterol," Dr. Lakoski said in an interview. "Fitness is a key risk factor for survival, and based on this study, an important factor to measure to assess future cancer risk and prognosis in men."

The study did not evaluate whether a particular type of exercise contributed more consistently to cardiovascular fitness, but in general, activities performed at high intensity, regardless of type, are the best way to improve fitness, she said.

Additional research is needed to determine fitness and cancer risk in women, fitness and risk of all major site-specific cancers and the necessary change in fitness to prevent cancer, Dr. Lakoski observed.

Assessment protocols and norms are available for CRF testing from the Cooper Institute.

Dr. Lakoski reported no relevant disclosures.

pwendling@frontlinemedcom.com

Measured levels of cardiorespiratory fitness appear to be as predictive of cancer risk and survival as they are of heart disease risk and survival, according to a 20-year, prospective study of more than 17,000 men.

The risks of lung and colorectal cancer were reduced 68% and 38%, respectively, in men with the highest level of cardiorespiratory fitness, compared with those who were the least fit.

Cardiorespiratory fitness did not significantly reduce prostate cancer risk, but the risk of dying was significantly lower among men with prostate, lung, or colorectal cancer if they were more fit in middle age (P less than .001).

Prior studies have shown that being physically active is protective against cancer, but this study is unique because it looked at a very specific marker – cardiorespiratory fitness as measured by maximal exercise tolerance testing, Dr. Susan G. Lakoski said during a press briefing highlighting research to be presented at the upcoming American Society of Clinical Oncology (ASCO) meeting.

"Fitness as formal measurement is known to prevent cardiovascular disease and it’s also known that it helps in terms of survival risk, but what hasn’t been known is does it prevent incident cancer and mortality after cancer diagnosis and that’s what’s elucidated in the current study," said Dr. Lakoski, director of the cardiovascular prevention program for cancer patients at the University of Vermont, Burlington.

She noted that several organizations, including the President’s Council on Fitness, Sports & Nutrition, are trying to measure fitness formally and that the American Heart Association has issued policy statements that fitness should be measured and normative values developed to determine cardiovascular risk.

"Fitness is a formal measurement; it’s sort of like measuring your LDL cholesterol, you get a very specific number to target," Dr. Lakoski said. "When you ask someone about their physical activity, you don’t get that information."

The 17,049 men in the study underwent exercise tolerance testing with a treadmill or bicycle and risk factor assessment at an average age of 50 years as part of the Cooper Center Longitudinal Study in Dallas. Metabolic equivalents (METs) were used to record the men’s cardiorespiratory fitness (CRF) and to place them into five CRF quintiles. Lung, colorectal and prostate cancers were assessed using Medicare claims data at Medicare age, and cause-specific mortality was determined after cancer diagnosis.

Over the 20 years of follow-up, 2,885 men were diagnosed with prostate, lung, or colorectal cancer and 769 died.

Compared with men in the lowest CRF quintile, hazard ratios (HR) for incident lung, colorectal and prostate cancer among men in the highest quintile were 0.32 (P less than .001), 0.62 (P = .05) and 1.13 (P = .14), after researchers adjusted for such risk factors as smoking, body mass index, and age, Dr. Lakoski reported.

In men who developed cancer, both cancer-specific mortality and cardiovascular-specific mortality declined across increasing CRF quintiles (P values less than .0001).

Even a single MET increase reduced the risk of dying from cancer and cardiovascular disease by 14% and 23%, respectively (HR, 0.86; HR, 0.77; P less than .001 for both measures), Dr. Lakoski said.

Another striking finding is that even if men aren’t obese, they still have an increased risk of cancer if they aren’t fit, "which suggests that everyone can benefit from improving their fitness," Dr. Sandra Swain, ASCO president and medical director of the Washington (D.C.) Cancer Institute told reporters.

"The findings make clear that patients should be advised that they need to achieve a certain fitness level, and not just be told that they need to exercise," Dr. Swain noted in a statement.

"A primary care physician should start to think about fitness in the same light as body weight or high cholesterol," Dr. Lakoski said in an interview. "Fitness is a key risk factor for survival, and based on this study, an important factor to measure to assess future cancer risk and prognosis in men."

The study did not evaluate whether a particular type of exercise contributed more consistently to cardiovascular fitness, but in general, activities performed at high intensity, regardless of type, are the best way to improve fitness, she said.

Additional research is needed to determine fitness and cancer risk in women, fitness and risk of all major site-specific cancers and the necessary change in fitness to prevent cancer, Dr. Lakoski observed.

Assessment protocols and norms are available for CRF testing from the Cooper Institute.

Dr. Lakoski reported no relevant disclosures.

pwendling@frontlinemedcom.com

Measured levels of cardiorespiratory fitness appear to be as predictive of cancer risk and survival as they are of heart disease risk and survival, according to a 20-year, prospective study of more than 17,000 men.

The risks of lung and colorectal cancer were reduced 68% and 38%, respectively, in men with the highest level of cardiorespiratory fitness, compared with those who were the least fit.

Cardiorespiratory fitness did not significantly reduce prostate cancer risk, but the risk of dying was significantly lower among men with prostate, lung, or colorectal cancer if they were more fit in middle age (P less than .001).

Prior studies have shown that being physically active is protective against cancer, but this study is unique because it looked at a very specific marker – cardiorespiratory fitness as measured by maximal exercise tolerance testing, Dr. Susan G. Lakoski said during a press briefing highlighting research to be presented at the upcoming American Society of Clinical Oncology (ASCO) meeting.

"Fitness as formal measurement is known to prevent cardiovascular disease and it’s also known that it helps in terms of survival risk, but what hasn’t been known is does it prevent incident cancer and mortality after cancer diagnosis and that’s what’s elucidated in the current study," said Dr. Lakoski, director of the cardiovascular prevention program for cancer patients at the University of Vermont, Burlington.

She noted that several organizations, including the President’s Council on Fitness, Sports & Nutrition, are trying to measure fitness formally and that the American Heart Association has issued policy statements that fitness should be measured and normative values developed to determine cardiovascular risk.

"Fitness is a formal measurement; it’s sort of like measuring your LDL cholesterol, you get a very specific number to target," Dr. Lakoski said. "When you ask someone about their physical activity, you don’t get that information."

The 17,049 men in the study underwent exercise tolerance testing with a treadmill or bicycle and risk factor assessment at an average age of 50 years as part of the Cooper Center Longitudinal Study in Dallas. Metabolic equivalents (METs) were used to record the men’s cardiorespiratory fitness (CRF) and to place them into five CRF quintiles. Lung, colorectal and prostate cancers were assessed using Medicare claims data at Medicare age, and cause-specific mortality was determined after cancer diagnosis.

Over the 20 years of follow-up, 2,885 men were diagnosed with prostate, lung, or colorectal cancer and 769 died.

Compared with men in the lowest CRF quintile, hazard ratios (HR) for incident lung, colorectal and prostate cancer among men in the highest quintile were 0.32 (P less than .001), 0.62 (P = .05) and 1.13 (P = .14), after researchers adjusted for such risk factors as smoking, body mass index, and age, Dr. Lakoski reported.

In men who developed cancer, both cancer-specific mortality and cardiovascular-specific mortality declined across increasing CRF quintiles (P values less than .0001).

Even a single MET increase reduced the risk of dying from cancer and cardiovascular disease by 14% and 23%, respectively (HR, 0.86; HR, 0.77; P less than .001 for both measures), Dr. Lakoski said.

Another striking finding is that even if men aren’t obese, they still have an increased risk of cancer if they aren’t fit, "which suggests that everyone can benefit from improving their fitness," Dr. Sandra Swain, ASCO president and medical director of the Washington (D.C.) Cancer Institute told reporters.

"The findings make clear that patients should be advised that they need to achieve a certain fitness level, and not just be told that they need to exercise," Dr. Swain noted in a statement.

"A primary care physician should start to think about fitness in the same light as body weight or high cholesterol," Dr. Lakoski said in an interview. "Fitness is a key risk factor for survival, and based on this study, an important factor to measure to assess future cancer risk and prognosis in men."

The study did not evaluate whether a particular type of exercise contributed more consistently to cardiovascular fitness, but in general, activities performed at high intensity, regardless of type, are the best way to improve fitness, she said.

Additional research is needed to determine fitness and cancer risk in women, fitness and risk of all major site-specific cancers and the necessary change in fitness to prevent cancer, Dr. Lakoski observed.

Assessment protocols and norms are available for CRF testing from the Cooper Institute.

Dr. Lakoski reported no relevant disclosures.

pwendling@frontlinemedcom.com