Breast Cancer

Adding 2 years of ovarian function suppression (OFS) to the standard 5-year regimen of tamoxifen could improve disease-free and overall survival in women with estrogen receptor–positive breast cancer who have been previously treated with chemotherapy and definitive surgery, according to results from the phase 3 ASTRRA trial.

The findings add support to recent results from the similarly designed Suppression of Ovarian Function Trial (SOFT), reported Hyun-Ah Kim, MD, PhD, of Korea Cancer Center Hospital, Seoul, and colleagues.

“Although OFS in breast cancer has been studied for decades and has been used widely in clinical practice, evidence for the benefits of adding OFS to standard adjuvant tamoxifen treatment is insufficient,” the investigators wrote in the Journal of Clinical Oncology.

The ASTRRA trial enrolled 1,483 premenopausal women aged 45 years or younger with estrogen receptor–positive breast cancer who had been previously treated with chemotherapy and definitive surgery. Of those, 1,293 women were randomized to receive either 5 years of tamoxifen, or the same regimen plus 2 years of OFS, at 35 treatment centers in South Korea. In all, 1,282 women were eligible for analysis.

The primary endpoint was disease-free survival, defined as secondary malignancy, invasive contralateral breast cancer, invasive local recurrence, regional recurrence, distant recurrence, or death from any cause. The secondary endpoint was overall survival.

After a median follow-up of 63 months, women who received OFS in addition to tamoxifen had an estimated disease-free survival rate of 91.1%, compared with 87.5% in those who received tamoxifen alone (P = .033). Similarly, adding OFS was associated with a better estimated 5-year overall survival rate, compared with standard monotherapy (99.4% vs. 97.8%; P = .029), Dr. Kim and associates said.

Despite having a shorter follow-up and smaller population size, the results from ASTRRA were similar to those from SOFT, most likely because ASTRRA patients had higher-risk disease, the investigators noted.

“The results of ASTRRA confirm the findings of SOFT, that the addition of OFS to tamoxifen provides survival benefits for women [who are] at sufficient risk for recurrence to receive adjuvant chemotherapy and who remain in a premenopausal state after chemotherapy,” they concluded.

The study was primarily funded by AstraZeneca, with additional support from the Korea Institute of Radiological and Medical Sciences. The investigators disclosed relationships with Novartis, Roche, Amgen, and others.

SOURCE: Kim HA et al. J Clin Oncol. 2019 Sep 16. doi: 10. 1200/JCO.19.00126.

Adding 2 years of ovarian function suppression (OFS) to the standard 5-year regimen of tamoxifen could improve disease-free and overall survival in women with estrogen receptor–positive breast cancer who have been previously treated with chemotherapy and definitive surgery, according to results from the phase 3 ASTRRA trial.

The findings add support to recent results from the similarly designed Suppression of Ovarian Function Trial (SOFT), reported Hyun-Ah Kim, MD, PhD, of Korea Cancer Center Hospital, Seoul, and colleagues.

“Although OFS in breast cancer has been studied for decades and has been used widely in clinical practice, evidence for the benefits of adding OFS to standard adjuvant tamoxifen treatment is insufficient,” the investigators wrote in the Journal of Clinical Oncology.

The ASTRRA trial enrolled 1,483 premenopausal women aged 45 years or younger with estrogen receptor–positive breast cancer who had been previously treated with chemotherapy and definitive surgery. Of those, 1,293 women were randomized to receive either 5 years of tamoxifen, or the same regimen plus 2 years of OFS, at 35 treatment centers in South Korea. In all, 1,282 women were eligible for analysis.

The primary endpoint was disease-free survival, defined as secondary malignancy, invasive contralateral breast cancer, invasive local recurrence, regional recurrence, distant recurrence, or death from any cause. The secondary endpoint was overall survival.

After a median follow-up of 63 months, women who received OFS in addition to tamoxifen had an estimated disease-free survival rate of 91.1%, compared with 87.5% in those who received tamoxifen alone (P = .033). Similarly, adding OFS was associated with a better estimated 5-year overall survival rate, compared with standard monotherapy (99.4% vs. 97.8%; P = .029), Dr. Kim and associates said.

Despite having a shorter follow-up and smaller population size, the results from ASTRRA were similar to those from SOFT, most likely because ASTRRA patients had higher-risk disease, the investigators noted.

“The results of ASTRRA confirm the findings of SOFT, that the addition of OFS to tamoxifen provides survival benefits for women [who are] at sufficient risk for recurrence to receive adjuvant chemotherapy and who remain in a premenopausal state after chemotherapy,” they concluded.

The study was primarily funded by AstraZeneca, with additional support from the Korea Institute of Radiological and Medical Sciences. The investigators disclosed relationships with Novartis, Roche, Amgen, and others.

SOURCE: Kim HA et al. J Clin Oncol. 2019 Sep 16. doi: 10. 1200/JCO.19.00126.

Adding 2 years of ovarian function suppression (OFS) to the standard 5-year regimen of tamoxifen could improve disease-free and overall survival in women with estrogen receptor–positive breast cancer who have been previously treated with chemotherapy and definitive surgery, according to results from the phase 3 ASTRRA trial.

The findings add support to recent results from the similarly designed Suppression of Ovarian Function Trial (SOFT), reported Hyun-Ah Kim, MD, PhD, of Korea Cancer Center Hospital, Seoul, and colleagues.

“Although OFS in breast cancer has been studied for decades and has been used widely in clinical practice, evidence for the benefits of adding OFS to standard adjuvant tamoxifen treatment is insufficient,” the investigators wrote in the Journal of Clinical Oncology.

The ASTRRA trial enrolled 1,483 premenopausal women aged 45 years or younger with estrogen receptor–positive breast cancer who had been previously treated with chemotherapy and definitive surgery. Of those, 1,293 women were randomized to receive either 5 years of tamoxifen, or the same regimen plus 2 years of OFS, at 35 treatment centers in South Korea. In all, 1,282 women were eligible for analysis.

The primary endpoint was disease-free survival, defined as secondary malignancy, invasive contralateral breast cancer, invasive local recurrence, regional recurrence, distant recurrence, or death from any cause. The secondary endpoint was overall survival.

After a median follow-up of 63 months, women who received OFS in addition to tamoxifen had an estimated disease-free survival rate of 91.1%, compared with 87.5% in those who received tamoxifen alone (P = .033). Similarly, adding OFS was associated with a better estimated 5-year overall survival rate, compared with standard monotherapy (99.4% vs. 97.8%; P = .029), Dr. Kim and associates said.

Despite having a shorter follow-up and smaller population size, the results from ASTRRA were similar to those from SOFT, most likely because ASTRRA patients had higher-risk disease, the investigators noted.

“The results of ASTRRA confirm the findings of SOFT, that the addition of OFS to tamoxifen provides survival benefits for women [who are] at sufficient risk for recurrence to receive adjuvant chemotherapy and who remain in a premenopausal state after chemotherapy,” they concluded.

The study was primarily funded by AstraZeneca, with additional support from the Korea Institute of Radiological and Medical Sciences. The investigators disclosed relationships with Novartis, Roche, Amgen, and others.

SOURCE: Kim HA et al. J Clin Oncol. 2019 Sep 16. doi: 10. 1200/JCO.19.00126.

The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.

“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.

The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.

CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.

Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.






 

The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.

“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.

The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.

CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.

Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.






 

The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.

“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.

The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.

CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.

Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.






 

Among women with HER2-positive metastatic breast cancer enrolled in a phase 2 randomized trial, the pan-ErbB inhibitor pyrotinib plus capecitabine had manageable toxicity and a significantly higher overall response rate (ORR) than lapatinib plus capecitabine, investigators reported.

The pyrotinib/capecitabine combination also led to significantly longer progression-free survival (PFS) versus that of standard lapatinib/capecitabine treatment in these women, who had previously received treatment with taxanes, anthracyclines, and in some cases trastuzumab, the investigators wrote in the Journal of Clinical Oncology.

“To our knowledge, this is the first trial to demonstrate that a novel epidermal growth factor receptor/HER2–targeting tyrosine kinase inhibitor provides ORR and PFS benefits over lapatinib,” wrote Fei Ma, MD, of the National Cancer Center, State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking, and colleagues.

In the phase 2 study, a total of 128 Chinese women with histologically confirmed relapsed or metastatic breast cancer were randomized to receive the pyrotinib- or lapatinib-containing regimens given in 21-day cycles.

Overall response rates, the primary end point, were 78% (51 of 65 patients) in the pyrotinib arm and 57.1% (36 of 63 patients) in the lapatinib arm (P = .01), Dr. Yu and colleagues reported.

Median PFS was 18.1 months versus 7.0 months in the pyrotinib and lapatinib arms, respectively (P less than .001). A “potential trend” toward improved overall survival was noted in the pyrotinib arm, though the data were premature and not statistically significant at the time of data analysis, according to the investigators.

Altogether, these efficacy results tracked with those of an earlier phase 1 investigation, and currently, a randomized phase 3 study is underway to confirm the findings, reported Dr. Yu and coauthors.

Hand-foot syndrome and diarrhea were the most common grade 3 adverse events seen with pyrotinib. The rate of grade 3 hand-foot syndrome wit pyrotinib was 24.6% versus 20.6% for the lapatinib group, and the rate of grade 3 diarrhea for the two groups was 15.4% and 4.8%, respectively.

Overall, grade 3 or 4 adverse events were seen in 61% of patients receiving pyrotinib, of which 3.1% were grade 4; they were seen in 47.6% of patients receiving lapatinib, of which 3.2% were grade 4.

Diarrhea of grade 3 severity occurred mainly in the first treatment cycle for both the pyrotinib and lapatinib groups, investigators said.

While the protocol for this randomized phase 2 study did not permit diarrhea prophylaxis, the use of prophylactic loperamide is being studied in a phase 3 study of pyrotinib plus trastuzumab and docetaxel in women with HER2-positive metastatic disease and no prior systemic therapy

Investigators said patients are told to interrupt capecitabine if they experience ongoing grade 3 diarrhea or grade 1 or 2 diarrhea with complications such as dehydration, nausea, vomiting, or fever. If the diarrhea persists after 3 days, pyrotinib should then be interrupted, they said.

Similar advice was given for hand-foot syndrome.

“To date, the only method proven to effectively manage hand-foot syndrome is interruption of treatment and, if necessary, dose reduction,” said the investigators, who recommended first interrupting capecitabine and later pyrotinib.

The study was sponsored by Jiangsu Hengrui Medicine and supported by the CAMS Initiative for Innovative Medicine and the National Science and Technology Major Project of the Ministry of Science and Technology in China. The corresponding author of this study, Binghe Xu, MD, PHD, reported institutional research funding from Jiangsu Hengrui Medicine and other disclosures related to AstraZeneca, Pfizer, Roche, and Eisai. Two study coauthors reported employment with Jiangsu Hengrui Medicine.

SOURCE: Ma F et al. J Clin Oncol. 2019 Aug 20. doi: 10.1200/JCO.19.00108.

Among women with HER2-positive metastatic breast cancer enrolled in a phase 2 randomized trial, the pan-ErbB inhibitor pyrotinib plus capecitabine had manageable toxicity and a significantly higher overall response rate (ORR) than lapatinib plus capecitabine, investigators reported.

The pyrotinib/capecitabine combination also led to significantly longer progression-free survival (PFS) versus that of standard lapatinib/capecitabine treatment in these women, who had previously received treatment with taxanes, anthracyclines, and in some cases trastuzumab, the investigators wrote in the Journal of Clinical Oncology.

“To our knowledge, this is the first trial to demonstrate that a novel epidermal growth factor receptor/HER2–targeting tyrosine kinase inhibitor provides ORR and PFS benefits over lapatinib,” wrote Fei Ma, MD, of the National Cancer Center, State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking, and colleagues.

In the phase 2 study, a total of 128 Chinese women with histologically confirmed relapsed or metastatic breast cancer were randomized to receive the pyrotinib- or lapatinib-containing regimens given in 21-day cycles.

Overall response rates, the primary end point, were 78% (51 of 65 patients) in the pyrotinib arm and 57.1% (36 of 63 patients) in the lapatinib arm (P = .01), Dr. Yu and colleagues reported.

Median PFS was 18.1 months versus 7.0 months in the pyrotinib and lapatinib arms, respectively (P less than .001). A “potential trend” toward improved overall survival was noted in the pyrotinib arm, though the data were premature and not statistically significant at the time of data analysis, according to the investigators.

Altogether, these efficacy results tracked with those of an earlier phase 1 investigation, and currently, a randomized phase 3 study is underway to confirm the findings, reported Dr. Yu and coauthors.

Hand-foot syndrome and diarrhea were the most common grade 3 adverse events seen with pyrotinib. The rate of grade 3 hand-foot syndrome wit pyrotinib was 24.6% versus 20.6% for the lapatinib group, and the rate of grade 3 diarrhea for the two groups was 15.4% and 4.8%, respectively.

Overall, grade 3 or 4 adverse events were seen in 61% of patients receiving pyrotinib, of which 3.1% were grade 4; they were seen in 47.6% of patients receiving lapatinib, of which 3.2% were grade 4.

Diarrhea of grade 3 severity occurred mainly in the first treatment cycle for both the pyrotinib and lapatinib groups, investigators said.

While the protocol for this randomized phase 2 study did not permit diarrhea prophylaxis, the use of prophylactic loperamide is being studied in a phase 3 study of pyrotinib plus trastuzumab and docetaxel in women with HER2-positive metastatic disease and no prior systemic therapy

Investigators said patients are told to interrupt capecitabine if they experience ongoing grade 3 diarrhea or grade 1 or 2 diarrhea with complications such as dehydration, nausea, vomiting, or fever. If the diarrhea persists after 3 days, pyrotinib should then be interrupted, they said.

Similar advice was given for hand-foot syndrome.

“To date, the only method proven to effectively manage hand-foot syndrome is interruption of treatment and, if necessary, dose reduction,” said the investigators, who recommended first interrupting capecitabine and later pyrotinib.

The study was sponsored by Jiangsu Hengrui Medicine and supported by the CAMS Initiative for Innovative Medicine and the National Science and Technology Major Project of the Ministry of Science and Technology in China. The corresponding author of this study, Binghe Xu, MD, PHD, reported institutional research funding from Jiangsu Hengrui Medicine and other disclosures related to AstraZeneca, Pfizer, Roche, and Eisai. Two study coauthors reported employment with Jiangsu Hengrui Medicine.

SOURCE: Ma F et al. J Clin Oncol. 2019 Aug 20. doi: 10.1200/JCO.19.00108.

Among women with HER2-positive metastatic breast cancer enrolled in a phase 2 randomized trial, the pan-ErbB inhibitor pyrotinib plus capecitabine had manageable toxicity and a significantly higher overall response rate (ORR) than lapatinib plus capecitabine, investigators reported.

The pyrotinib/capecitabine combination also led to significantly longer progression-free survival (PFS) versus that of standard lapatinib/capecitabine treatment in these women, who had previously received treatment with taxanes, anthracyclines, and in some cases trastuzumab, the investigators wrote in the Journal of Clinical Oncology.

“To our knowledge, this is the first trial to demonstrate that a novel epidermal growth factor receptor/HER2–targeting tyrosine kinase inhibitor provides ORR and PFS benefits over lapatinib,” wrote Fei Ma, MD, of the National Cancer Center, State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking, and colleagues.

In the phase 2 study, a total of 128 Chinese women with histologically confirmed relapsed or metastatic breast cancer were randomized to receive the pyrotinib- or lapatinib-containing regimens given in 21-day cycles.

Overall response rates, the primary end point, were 78% (51 of 65 patients) in the pyrotinib arm and 57.1% (36 of 63 patients) in the lapatinib arm (P = .01), Dr. Yu and colleagues reported.

Median PFS was 18.1 months versus 7.0 months in the pyrotinib and lapatinib arms, respectively (P less than .001). A “potential trend” toward improved overall survival was noted in the pyrotinib arm, though the data were premature and not statistically significant at the time of data analysis, according to the investigators.

Altogether, these efficacy results tracked with those of an earlier phase 1 investigation, and currently, a randomized phase 3 study is underway to confirm the findings, reported Dr. Yu and coauthors.

Hand-foot syndrome and diarrhea were the most common grade 3 adverse events seen with pyrotinib. The rate of grade 3 hand-foot syndrome wit pyrotinib was 24.6% versus 20.6% for the lapatinib group, and the rate of grade 3 diarrhea for the two groups was 15.4% and 4.8%, respectively.

Overall, grade 3 or 4 adverse events were seen in 61% of patients receiving pyrotinib, of which 3.1% were grade 4; they were seen in 47.6% of patients receiving lapatinib, of which 3.2% were grade 4.

Diarrhea of grade 3 severity occurred mainly in the first treatment cycle for both the pyrotinib and lapatinib groups, investigators said.

While the protocol for this randomized phase 2 study did not permit diarrhea prophylaxis, the use of prophylactic loperamide is being studied in a phase 3 study of pyrotinib plus trastuzumab and docetaxel in women with HER2-positive metastatic disease and no prior systemic therapy

Investigators said patients are told to interrupt capecitabine if they experience ongoing grade 3 diarrhea or grade 1 or 2 diarrhea with complications such as dehydration, nausea, vomiting, or fever. If the diarrhea persists after 3 days, pyrotinib should then be interrupted, they said.

Similar advice was given for hand-foot syndrome.

“To date, the only method proven to effectively manage hand-foot syndrome is interruption of treatment and, if necessary, dose reduction,” said the investigators, who recommended first interrupting capecitabine and later pyrotinib.

The study was sponsored by Jiangsu Hengrui Medicine and supported by the CAMS Initiative for Innovative Medicine and the National Science and Technology Major Project of the Ministry of Science and Technology in China. The corresponding author of this study, Binghe Xu, MD, PHD, reported institutional research funding from Jiangsu Hengrui Medicine and other disclosures related to AstraZeneca, Pfizer, Roche, and Eisai. Two study coauthors reported employment with Jiangsu Hengrui Medicine.

SOURCE: Ma F et al. J Clin Oncol. 2019 Aug 20. doi: 10.1200/JCO.19.00108.

Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.

Dr. Cecil Fox/National Cancer Institute

SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.

Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.

Dr. Cecil Fox/National Cancer Institute

SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.

Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.

Dr. Cecil Fox/National Cancer Institute

SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.

In women with nonmetastatic breast cancer, postoperative regional node irradiation with proton-beam radiation was associated with low rates of toxicity and with disease control rates similar to those reported with conventional photon-based radiation therapy (RT), investigators in a small prospective clinical study reported.

Among 62 survivors of a cohort of 69 women with nonmetastatic breast cancer who required postoperative radiation to the internal mammary nodes (IMN) and for whom conventional radiation was thought to pose excess risks of toxicity, there were no cases of the primary endpoint of grade 3 or greater radiation pneumonitis and no grade 4 toxicities within 3 months of therapy, reported Rachel B. Jimenez, MD, of the Massachusetts General Hospital Cancer Center in Boston and colleagues.

“In our prospective trial of women with locally advanced breast cancer who required treatment of the IMNs, proton beam RT was safe and effective. Future research will provide needed information about the potential long-term normal tissue–sparing benefits of this complex treatment modality compared with conventional radiation,” they wrote in the Journal of Clinical Oncology.

Protons offer the theoretic advantage over photons of minimizing radiation dose to the heart and lungs when treating the breast, chest wall, or regional lymph nodes. Protons, unlike photons, deliver their maximum ionizing energy to tissues immediately before they come to rest, allowing for a more precise dose of radiation to local tissues.

“Multiple dosimetric planning studies that compared proton RT with photon RT have demonstrated superior delivery to targeted areas while sparing more of the heart and lungs. However, prospective clinical data are lacking to support the safety and efficacy of proton RT for breast cancer,” the investigators wrote.

To rectify this, they enrolled adult patients with nonmetastatic breast cancer who required postoperative radiation therapy inclusive of the IMNs and for whom the treating physician determined that either breast reconstruction would prevent adequate target coverage or conventional radiation would deliver 20 Gy or more to 5% or more of the heart and/or the left anterior descending artery (LAD).

A total of 69 patients (median age 45 years) were evaluable for the primary endpoint. In all, 63 of the 70 enrolled patients had left-sided breast cancer, 5 had right-sided breast cancer, and 2 had bilateral breast cancer. The majority of patients (65) had stage II-III disease. All but 2 patients underwent systemic chemotherapy, and 50 underwent immediate reconstruction.

The median of the mean proton radiation dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the IMN was 48.8 Gy (relative biological effectiveness), indicating comprehensive coverage. The mean heart dose was a median of 0.50 Gy, and the mean dose to the LAD was a median of 1.16 Gy.

After a median follow-up of 55 months, the 5-year rate for locoregional failure among 62 surviving patients was 1.5%

As noted before, there were no cases of grade 3 radiation pneumonitis and no grade 4 toxicities of any type within 3 months of radiation therapy. One patient developed grade 2 radiation pneumonitis 4 months after therapy and was successfully treated with oral corticosteroids, and one developed a severe infection of the bilateral chest wall 4 months after radiation to the left-side chest wall. She was treated with intravenous antibiotics.

There were no significant changes in either echocardiography or cardiac biomarkers after radiotherapy.

The authors noted that the toxicity and disease control rates compared favorably with those of historical data on conventional radiation therapy from two studies published in 2015 (N Engl J Med. 2015;373:307-16; N Engl J Med. 2015;373:317-27).

The study was supported by a grant from the National Institutes of Health. Dr. Jimenez disclosed research funding from Focal Therapeutics.

SOURCE: Jimenez RB et al. J Clin Oncol 2019 Aug 26. doi: 10.1200/JCO.18.02366.

In women with nonmetastatic breast cancer, postoperative regional node irradiation with proton-beam radiation was associated with low rates of toxicity and with disease control rates similar to those reported with conventional photon-based radiation therapy (RT), investigators in a small prospective clinical study reported.

Among 62 survivors of a cohort of 69 women with nonmetastatic breast cancer who required postoperative radiation to the internal mammary nodes (IMN) and for whom conventional radiation was thought to pose excess risks of toxicity, there were no cases of the primary endpoint of grade 3 or greater radiation pneumonitis and no grade 4 toxicities within 3 months of therapy, reported Rachel B. Jimenez, MD, of the Massachusetts General Hospital Cancer Center in Boston and colleagues.

“In our prospective trial of women with locally advanced breast cancer who required treatment of the IMNs, proton beam RT was safe and effective. Future research will provide needed information about the potential long-term normal tissue–sparing benefits of this complex treatment modality compared with conventional radiation,” they wrote in the Journal of Clinical Oncology.

Protons offer the theoretic advantage over photons of minimizing radiation dose to the heart and lungs when treating the breast, chest wall, or regional lymph nodes. Protons, unlike photons, deliver their maximum ionizing energy to tissues immediately before they come to rest, allowing for a more precise dose of radiation to local tissues.

“Multiple dosimetric planning studies that compared proton RT with photon RT have demonstrated superior delivery to targeted areas while sparing more of the heart and lungs. However, prospective clinical data are lacking to support the safety and efficacy of proton RT for breast cancer,” the investigators wrote.

To rectify this, they enrolled adult patients with nonmetastatic breast cancer who required postoperative radiation therapy inclusive of the IMNs and for whom the treating physician determined that either breast reconstruction would prevent adequate target coverage or conventional radiation would deliver 20 Gy or more to 5% or more of the heart and/or the left anterior descending artery (LAD).

A total of 69 patients (median age 45 years) were evaluable for the primary endpoint. In all, 63 of the 70 enrolled patients had left-sided breast cancer, 5 had right-sided breast cancer, and 2 had bilateral breast cancer. The majority of patients (65) had stage II-III disease. All but 2 patients underwent systemic chemotherapy, and 50 underwent immediate reconstruction.

The median of the mean proton radiation dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the IMN was 48.8 Gy (relative biological effectiveness), indicating comprehensive coverage. The mean heart dose was a median of 0.50 Gy, and the mean dose to the LAD was a median of 1.16 Gy.

After a median follow-up of 55 months, the 5-year rate for locoregional failure among 62 surviving patients was 1.5%

As noted before, there were no cases of grade 3 radiation pneumonitis and no grade 4 toxicities of any type within 3 months of radiation therapy. One patient developed grade 2 radiation pneumonitis 4 months after therapy and was successfully treated with oral corticosteroids, and one developed a severe infection of the bilateral chest wall 4 months after radiation to the left-side chest wall. She was treated with intravenous antibiotics.

There were no significant changes in either echocardiography or cardiac biomarkers after radiotherapy.

The authors noted that the toxicity and disease control rates compared favorably with those of historical data on conventional radiation therapy from two studies published in 2015 (N Engl J Med. 2015;373:307-16; N Engl J Med. 2015;373:317-27).

The study was supported by a grant from the National Institutes of Health. Dr. Jimenez disclosed research funding from Focal Therapeutics.

SOURCE: Jimenez RB et al. J Clin Oncol 2019 Aug 26. doi: 10.1200/JCO.18.02366.

In women with nonmetastatic breast cancer, postoperative regional node irradiation with proton-beam radiation was associated with low rates of toxicity and with disease control rates similar to those reported with conventional photon-based radiation therapy (RT), investigators in a small prospective clinical study reported.

Among 62 survivors of a cohort of 69 women with nonmetastatic breast cancer who required postoperative radiation to the internal mammary nodes (IMN) and for whom conventional radiation was thought to pose excess risks of toxicity, there were no cases of the primary endpoint of grade 3 or greater radiation pneumonitis and no grade 4 toxicities within 3 months of therapy, reported Rachel B. Jimenez, MD, of the Massachusetts General Hospital Cancer Center in Boston and colleagues.

“In our prospective trial of women with locally advanced breast cancer who required treatment of the IMNs, proton beam RT was safe and effective. Future research will provide needed information about the potential long-term normal tissue–sparing benefits of this complex treatment modality compared with conventional radiation,” they wrote in the Journal of Clinical Oncology.

Protons offer the theoretic advantage over photons of minimizing radiation dose to the heart and lungs when treating the breast, chest wall, or regional lymph nodes. Protons, unlike photons, deliver their maximum ionizing energy to tissues immediately before they come to rest, allowing for a more precise dose of radiation to local tissues.

“Multiple dosimetric planning studies that compared proton RT with photon RT have demonstrated superior delivery to targeted areas while sparing more of the heart and lungs. However, prospective clinical data are lacking to support the safety and efficacy of proton RT for breast cancer,” the investigators wrote.

To rectify this, they enrolled adult patients with nonmetastatic breast cancer who required postoperative radiation therapy inclusive of the IMNs and for whom the treating physician determined that either breast reconstruction would prevent adequate target coverage or conventional radiation would deliver 20 Gy or more to 5% or more of the heart and/or the left anterior descending artery (LAD).

A total of 69 patients (median age 45 years) were evaluable for the primary endpoint. In all, 63 of the 70 enrolled patients had left-sided breast cancer, 5 had right-sided breast cancer, and 2 had bilateral breast cancer. The majority of patients (65) had stage II-III disease. All but 2 patients underwent systemic chemotherapy, and 50 underwent immediate reconstruction.

The median of the mean proton radiation dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the IMN was 48.8 Gy (relative biological effectiveness), indicating comprehensive coverage. The mean heart dose was a median of 0.50 Gy, and the mean dose to the LAD was a median of 1.16 Gy.

After a median follow-up of 55 months, the 5-year rate for locoregional failure among 62 surviving patients was 1.5%

As noted before, there were no cases of grade 3 radiation pneumonitis and no grade 4 toxicities of any type within 3 months of radiation therapy. One patient developed grade 2 radiation pneumonitis 4 months after therapy and was successfully treated with oral corticosteroids, and one developed a severe infection of the bilateral chest wall 4 months after radiation to the left-side chest wall. She was treated with intravenous antibiotics.

There were no significant changes in either echocardiography or cardiac biomarkers after radiotherapy.

The authors noted that the toxicity and disease control rates compared favorably with those of historical data on conventional radiation therapy from two studies published in 2015 (N Engl J Med. 2015;373:307-16; N Engl J Med. 2015;373:317-27).

The study was supported by a grant from the National Institutes of Health. Dr. Jimenez disclosed research funding from Focal Therapeutics.

SOURCE: Jimenez RB et al. J Clin Oncol 2019 Aug 26. doi: 10.1200/JCO.18.02366.

The combination of ado-trastuzumab emtansine (T-DM1) and neratinib shows promise in patients with HER2-positive metastatic breast cancer, according to results from a phase 1b trial.

“The purpose of this study was to determine the safety and preliminary efficacy of the combination in patients previously treated with trastuzumab plus pertuzumab,” wrote Jame Abraham, MD, of the Cleveland Clinic and colleagues in the Journal of Clinical Oncology.

The open-label, dose-escalation study included 27 women with HER2-positive metastatic breast cancer who had hormone receptor–positive or hormone receptor–negative disease. All participants had demonstrated disease progression, despite prior treatment with combination pertuzumab and trastuzumab, plus a taxane. Among 19 response-evaluable patients, 12 patients (63%) had an objective response. Responses were observed across all neratinib doses, including a complete response in three patients, and partial response in nine patients.

“Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification,” Dr. Abraham and associates noted.

“Alterations in the expression of specific HER2 species in ERBB2-amplified cancers, including p95HER2, may have therapeutic implications and require further investigation,” they wrote.

With respect to neratinib dosing, the initial cohort was started at 120 mg daily, which was increased to 240 mg daily in successive cohorts using a 3+3 design. T-DM1 was administered every 3 weeks at 3.6 mg/kg.

After analysis, the researchers proposed a phase 2 dose of neratinib 160 mg once daily and T-DM1 3.6 mg/kg for the combination.

Dose-limiting grade 3 diarrhea was reported in a total of six patients, which was most pronounced in cycle 1. At the phase 2 recommended dose of neratinib, 7 of 10 patients had early-onset diarrhea, which resolved within 24 hours. No grade 4-5 diarrheal toxicities were reported.

Other grade 3-4 adverse events observed were electrolyte abnormalities, thrombocytopenia, nausea, and dehydration.

Phase 2 studies are currently ongoing in order to better characterize the activity of combination T-DM1 and neratinib.

The study was funded by PUMA Biotechnology and the University of Pittsburgh. The authors reported financial affiliations with AstraZeneca, Eisai, Genentech, Guardant Health, Pfizer, Roche, Seattle Genetics, and several others.

SOURCE: Abraham J et al. J Clin Oncol. 2019 Aug 23. doi: 10.1200/JCO.19.00858.

The combination of ado-trastuzumab emtansine (T-DM1) and neratinib shows promise in patients with HER2-positive metastatic breast cancer, according to results from a phase 1b trial.

“The purpose of this study was to determine the safety and preliminary efficacy of the combination in patients previously treated with trastuzumab plus pertuzumab,” wrote Jame Abraham, MD, of the Cleveland Clinic and colleagues in the Journal of Clinical Oncology.

The open-label, dose-escalation study included 27 women with HER2-positive metastatic breast cancer who had hormone receptor–positive or hormone receptor–negative disease. All participants had demonstrated disease progression, despite prior treatment with combination pertuzumab and trastuzumab, plus a taxane. Among 19 response-evaluable patients, 12 patients (63%) had an objective response. Responses were observed across all neratinib doses, including a complete response in three patients, and partial response in nine patients.

“Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification,” Dr. Abraham and associates noted.

“Alterations in the expression of specific HER2 species in ERBB2-amplified cancers, including p95HER2, may have therapeutic implications and require further investigation,” they wrote.

With respect to neratinib dosing, the initial cohort was started at 120 mg daily, which was increased to 240 mg daily in successive cohorts using a 3+3 design. T-DM1 was administered every 3 weeks at 3.6 mg/kg.

After analysis, the researchers proposed a phase 2 dose of neratinib 160 mg once daily and T-DM1 3.6 mg/kg for the combination.

Dose-limiting grade 3 diarrhea was reported in a total of six patients, which was most pronounced in cycle 1. At the phase 2 recommended dose of neratinib, 7 of 10 patients had early-onset diarrhea, which resolved within 24 hours. No grade 4-5 diarrheal toxicities were reported.

Other grade 3-4 adverse events observed were electrolyte abnormalities, thrombocytopenia, nausea, and dehydration.

Phase 2 studies are currently ongoing in order to better characterize the activity of combination T-DM1 and neratinib.

The study was funded by PUMA Biotechnology and the University of Pittsburgh. The authors reported financial affiliations with AstraZeneca, Eisai, Genentech, Guardant Health, Pfizer, Roche, Seattle Genetics, and several others.

SOURCE: Abraham J et al. J Clin Oncol. 2019 Aug 23. doi: 10.1200/JCO.19.00858.

The combination of ado-trastuzumab emtansine (T-DM1) and neratinib shows promise in patients with HER2-positive metastatic breast cancer, according to results from a phase 1b trial.

“The purpose of this study was to determine the safety and preliminary efficacy of the combination in patients previously treated with trastuzumab plus pertuzumab,” wrote Jame Abraham, MD, of the Cleveland Clinic and colleagues in the Journal of Clinical Oncology.

The open-label, dose-escalation study included 27 women with HER2-positive metastatic breast cancer who had hormone receptor–positive or hormone receptor–negative disease. All participants had demonstrated disease progression, despite prior treatment with combination pertuzumab and trastuzumab, plus a taxane. Among 19 response-evaluable patients, 12 patients (63%) had an objective response. Responses were observed across all neratinib doses, including a complete response in three patients, and partial response in nine patients.

“Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification,” Dr. Abraham and associates noted.

“Alterations in the expression of specific HER2 species in ERBB2-amplified cancers, including p95HER2, may have therapeutic implications and require further investigation,” they wrote.

With respect to neratinib dosing, the initial cohort was started at 120 mg daily, which was increased to 240 mg daily in successive cohorts using a 3+3 design. T-DM1 was administered every 3 weeks at 3.6 mg/kg.

After analysis, the researchers proposed a phase 2 dose of neratinib 160 mg once daily and T-DM1 3.6 mg/kg for the combination.

Dose-limiting grade 3 diarrhea was reported in a total of six patients, which was most pronounced in cycle 1. At the phase 2 recommended dose of neratinib, 7 of 10 patients had early-onset diarrhea, which resolved within 24 hours. No grade 4-5 diarrheal toxicities were reported.

Other grade 3-4 adverse events observed were electrolyte abnormalities, thrombocytopenia, nausea, and dehydration.

Phase 2 studies are currently ongoing in order to better characterize the activity of combination T-DM1 and neratinib.

The study was funded by PUMA Biotechnology and the University of Pittsburgh. The authors reported financial affiliations with AstraZeneca, Eisai, Genentech, Guardant Health, Pfizer, Roche, Seattle Genetics, and several others.

SOURCE: Abraham J et al. J Clin Oncol. 2019 Aug 23. doi: 10.1200/JCO.19.00858.

When it comes to treatment recommendations for high-risk breast cancer, oncologists agree with a leading artificial intelligence platform about half the time, according to investigators.

In the first study of its kind, involving 10 Chinese oncologists, recommendation concordance with the Watson for Oncology treatment advisory tool (WfO) was generally lower for hormone receptor–positive and metastatic cancers than hormone receptor–negative and nonmetastatic cases, reported Fengrui Xu, MD, of the Academy of Military Medical Sciences in Beijing, and colleagues. Refinement could enable broad use of Watson, not to dictate treatment decisions, but instead to propose alternate treatment approaches and offer point-of-care access to relevant evidence.

“[WfO] is an example of a quantitative oncology clinical decision support that leverages the clinical expertise of oncologists at Memorial Sloan Kettering Cancer Center [MSKCC],” the investigators wrote in JCO Clinical Cancer Informatics. The platform uses machine-learning software to interpret patient scenarios in light from MSKCC training cases, MSKCC treatment guidelines, and more than 300 medical textbooks and journals.

To compare WfO with real-world decision makers, the investigators recruited three chief physicians, four attending physicians, and three fellows to provide treatment recommendations for 1,977 patients with complex breast cancer who were treated at 10 hospitals in China. Participating physicians shared the workload; each evaluated an average of 198 different cases.

On average, oncologists and WfO made the same treatment recommendations 56% of the time. Out of the different types of physicians, fellows were most likely to agree with WfO, based on a 68% concordance rate, compared with 54% for chief physicians and 49% for attending physicians. Including all physicians, concordance was lowest for hormone receptor–positive/HER2-positive disease (48%) and highest for triple-negative cases (71%). Adjuvant and metastatic therapies were also evaluated, with high concordance for adjuvant endocrine (78%) and targeted therapy (100%), compared with moderate concordance for first- (52%) and second-line metastatic therapy (50%). The investigators described concordance results as generally “modest;” however, they noted that such levels are promising.

“This degree of concordance is encouraging because therapeutic decisions in these cases are often difficult as a result of the current limits of medical knowledge for treating complex breast cancers and the presence of local contextual factors that affect physician treatment choices,” the investigators wrote. “It is important to note that nonconcordance does not imply that one treatment is correct for a given patient and another is not, nor does it necessarily diminish the potential value of a decision support system that provides access to supporting evidence and insight into its reasoning process.”

The study was funded by Zefei Jiang. The investigators reported affiliations with IBM Watson Health, Pharmaceutical Manufacturer Institution, Merck, and others.

SOURCE: Xu F et al. JCO Clin Cancer Inform. 2019 Aug 16. doi: 10.1200/CCI.18.00159.

When it comes to treatment recommendations for high-risk breast cancer, oncologists agree with a leading artificial intelligence platform about half the time, according to investigators.

In the first study of its kind, involving 10 Chinese oncologists, recommendation concordance with the Watson for Oncology treatment advisory tool (WfO) was generally lower for hormone receptor–positive and metastatic cancers than hormone receptor–negative and nonmetastatic cases, reported Fengrui Xu, MD, of the Academy of Military Medical Sciences in Beijing, and colleagues. Refinement could enable broad use of Watson, not to dictate treatment decisions, but instead to propose alternate treatment approaches and offer point-of-care access to relevant evidence.

“[WfO] is an example of a quantitative oncology clinical decision support that leverages the clinical expertise of oncologists at Memorial Sloan Kettering Cancer Center [MSKCC],” the investigators wrote in JCO Clinical Cancer Informatics. The platform uses machine-learning software to interpret patient scenarios in light from MSKCC training cases, MSKCC treatment guidelines, and more than 300 medical textbooks and journals.

To compare WfO with real-world decision makers, the investigators recruited three chief physicians, four attending physicians, and three fellows to provide treatment recommendations for 1,977 patients with complex breast cancer who were treated at 10 hospitals in China. Participating physicians shared the workload; each evaluated an average of 198 different cases.

On average, oncologists and WfO made the same treatment recommendations 56% of the time. Out of the different types of physicians, fellows were most likely to agree with WfO, based on a 68% concordance rate, compared with 54% for chief physicians and 49% for attending physicians. Including all physicians, concordance was lowest for hormone receptor–positive/HER2-positive disease (48%) and highest for triple-negative cases (71%). Adjuvant and metastatic therapies were also evaluated, with high concordance for adjuvant endocrine (78%) and targeted therapy (100%), compared with moderate concordance for first- (52%) and second-line metastatic therapy (50%). The investigators described concordance results as generally “modest;” however, they noted that such levels are promising.

“This degree of concordance is encouraging because therapeutic decisions in these cases are often difficult as a result of the current limits of medical knowledge for treating complex breast cancers and the presence of local contextual factors that affect physician treatment choices,” the investigators wrote. “It is important to note that nonconcordance does not imply that one treatment is correct for a given patient and another is not, nor does it necessarily diminish the potential value of a decision support system that provides access to supporting evidence and insight into its reasoning process.”

The study was funded by Zefei Jiang. The investigators reported affiliations with IBM Watson Health, Pharmaceutical Manufacturer Institution, Merck, and others.

SOURCE: Xu F et al. JCO Clin Cancer Inform. 2019 Aug 16. doi: 10.1200/CCI.18.00159.

When it comes to treatment recommendations for high-risk breast cancer, oncologists agree with a leading artificial intelligence platform about half the time, according to investigators.

In the first study of its kind, involving 10 Chinese oncologists, recommendation concordance with the Watson for Oncology treatment advisory tool (WfO) was generally lower for hormone receptor–positive and metastatic cancers than hormone receptor–negative and nonmetastatic cases, reported Fengrui Xu, MD, of the Academy of Military Medical Sciences in Beijing, and colleagues. Refinement could enable broad use of Watson, not to dictate treatment decisions, but instead to propose alternate treatment approaches and offer point-of-care access to relevant evidence.

“[WfO] is an example of a quantitative oncology clinical decision support that leverages the clinical expertise of oncologists at Memorial Sloan Kettering Cancer Center [MSKCC],” the investigators wrote in JCO Clinical Cancer Informatics. The platform uses machine-learning software to interpret patient scenarios in light from MSKCC training cases, MSKCC treatment guidelines, and more than 300 medical textbooks and journals.

To compare WfO with real-world decision makers, the investigators recruited three chief physicians, four attending physicians, and three fellows to provide treatment recommendations for 1,977 patients with complex breast cancer who were treated at 10 hospitals in China. Participating physicians shared the workload; each evaluated an average of 198 different cases.

On average, oncologists and WfO made the same treatment recommendations 56% of the time. Out of the different types of physicians, fellows were most likely to agree with WfO, based on a 68% concordance rate, compared with 54% for chief physicians and 49% for attending physicians. Including all physicians, concordance was lowest for hormone receptor–positive/HER2-positive disease (48%) and highest for triple-negative cases (71%). Adjuvant and metastatic therapies were also evaluated, with high concordance for adjuvant endocrine (78%) and targeted therapy (100%), compared with moderate concordance for first- (52%) and second-line metastatic therapy (50%). The investigators described concordance results as generally “modest;” however, they noted that such levels are promising.

“This degree of concordance is encouraging because therapeutic decisions in these cases are often difficult as a result of the current limits of medical knowledge for treating complex breast cancers and the presence of local contextual factors that affect physician treatment choices,” the investigators wrote. “It is important to note that nonconcordance does not imply that one treatment is correct for a given patient and another is not, nor does it necessarily diminish the potential value of a decision support system that provides access to supporting evidence and insight into its reasoning process.”

The study was funded by Zefei Jiang. The investigators reported affiliations with IBM Watson Health, Pharmaceutical Manufacturer Institution, Merck, and others.

SOURCE: Xu F et al. JCO Clin Cancer Inform. 2019 Aug 16. doi: 10.1200/CCI.18.00159.

Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.

A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.

The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.

Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.

The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.

Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.

“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.

They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.

“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”

The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.

SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.

Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.

A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.

The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.

Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.

The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.

Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.

“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.

They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.

“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”

The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.

SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.

Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.

A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.

The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.

Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.

The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.

Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.

“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.

They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.

“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”

The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.

SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.