Key clinical point: Specific predictors for postoperative 90-day mortality for hepatocellular carcinoma patients after hepatic resection include Child-Pugh score, intraoperative blood loss, post-hepatectomy liver failure (PHLF), and peak serum bilirubin.

Major finding: The overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. 

Study details: The data come from a retrospective study of 244 adults with HCC who underwent elective hepatic resection between January 1, 2007, and December 31, 2017. 

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Lei GY et al. Visc Med. 2020 Oct 27. doi: 10.1159/000510811.

Key clinical point: Specific predictors for postoperative 90-day mortality for hepatocellular carcinoma patients after hepatic resection include Child-Pugh score, intraoperative blood loss, post-hepatectomy liver failure (PHLF), and peak serum bilirubin.

Major finding: The overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. 

Study details: The data come from a retrospective study of 244 adults with HCC who underwent elective hepatic resection between January 1, 2007, and December 31, 2017. 

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Lei GY et al. Visc Med. 2020 Oct 27. doi: 10.1159/000510811.

Key clinical point: Specific predictors for postoperative 90-day mortality for hepatocellular carcinoma patients after hepatic resection include Child-Pugh score, intraoperative blood loss, post-hepatectomy liver failure (PHLF), and peak serum bilirubin.

Major finding: The overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. 

Study details: The data come from a retrospective study of 244 adults with HCC who underwent elective hepatic resection between January 1, 2007, and December 31, 2017. 

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Lei GY et al. Visc Med. 2020 Oct 27. doi: 10.1159/000510811.

Key clinical point: The DEPDC1B gene restrained growth of tumors associated with HCC progression both in vitro and in vivo.

Major finding: Knockdown of DEPDC1B inhibited the progression of HCC by inhibiting cell proliferation, migration, and colony formation, also by promoting cell apoptosis in vitro.

Study details: The data come from an in vitro and in vivo analysis of DEPDC1B using immunohistochemical staining to detect expression in tumor tissues and normal tissues, and a  xenograft model was used to show the functions of DEPC1B on tumor growth in vivo.

Disclosures: The study was supported by the National Natural Science Foundation of China (No. 81602100) and Natural Science Foundation of Shanghai. The researchers had no financial conflicts to disclose.  

Source: Dang X-W et al. Aging. 2021 May 25. doi: 10.18632/aging.203016.

Key clinical point: The DEPDC1B gene restrained growth of tumors associated with HCC progression both in vitro and in vivo.

Major finding: Knockdown of DEPDC1B inhibited the progression of HCC by inhibiting cell proliferation, migration, and colony formation, also by promoting cell apoptosis in vitro.

Study details: The data come from an in vitro and in vivo analysis of DEPDC1B using immunohistochemical staining to detect expression in tumor tissues and normal tissues, and a  xenograft model was used to show the functions of DEPC1B on tumor growth in vivo.

Disclosures: The study was supported by the National Natural Science Foundation of China (No. 81602100) and Natural Science Foundation of Shanghai. The researchers had no financial conflicts to disclose.  

Source: Dang X-W et al. Aging. 2021 May 25. doi: 10.18632/aging.203016.

Key clinical point: The DEPDC1B gene restrained growth of tumors associated with HCC progression both in vitro and in vivo.

Major finding: Knockdown of DEPDC1B inhibited the progression of HCC by inhibiting cell proliferation, migration, and colony formation, also by promoting cell apoptosis in vitro.

Study details: The data come from an in vitro and in vivo analysis of DEPDC1B using immunohistochemical staining to detect expression in tumor tissues and normal tissues, and a  xenograft model was used to show the functions of DEPC1B on tumor growth in vivo.

Disclosures: The study was supported by the National Natural Science Foundation of China (No. 81602100) and Natural Science Foundation of Shanghai. The researchers had no financial conflicts to disclose.  

Source: Dang X-W et al. Aging. 2021 May 25. doi: 10.18632/aging.203016.

Key clinical point: No single first-line treatment for advanced hepatocellular carcinoma demonstrated superior outcomes across all measures, therefore treatment should be based on individual goals.

Major finding: Lenvatinib ranked highest for overall response rate for patients with advanced/unresectable HCC, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival, the top-ranked treatments was atezolizumab + bevacizumab, followed by lenvatinib.

Study details: The data come from a meta-analysis of 27 randomized, controlled trials of first-line therapies for hepatocellular carcinoma. The treatments compared in the studies were Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and 3 other combination therapies. 

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Han Y et al. World J. Gastroenterol. 2021 May 21. doi: 10.3748/wjg.v27.i19.2415.

Key clinical point: No single first-line treatment for advanced hepatocellular carcinoma demonstrated superior outcomes across all measures, therefore treatment should be based on individual goals.

Major finding: Lenvatinib ranked highest for overall response rate for patients with advanced/unresectable HCC, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival, the top-ranked treatments was atezolizumab + bevacizumab, followed by lenvatinib.

Study details: The data come from a meta-analysis of 27 randomized, controlled trials of first-line therapies for hepatocellular carcinoma. The treatments compared in the studies were Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and 3 other combination therapies. 

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Han Y et al. World J. Gastroenterol. 2021 May 21. doi: 10.3748/wjg.v27.i19.2415.

Key clinical point: No single first-line treatment for advanced hepatocellular carcinoma demonstrated superior outcomes across all measures, therefore treatment should be based on individual goals.

Major finding: Lenvatinib ranked highest for overall response rate for patients with advanced/unresectable HCC, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival, the top-ranked treatments was atezolizumab + bevacizumab, followed by lenvatinib.

Study details: The data come from a meta-analysis of 27 randomized, controlled trials of first-line therapies for hepatocellular carcinoma. The treatments compared in the studies were Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and 3 other combination therapies. 

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Han Y et al. World J. Gastroenterol. 2021 May 21. doi: 10.3748/wjg.v27.i19.2415.

Key clinical point: The EZ albumin-bilirubin (ALBI) score was significantly correlated with the original and more complex ALBI score as a biomarker of liver injury.

Major finding: The correlation coefficient of the EZ-ALBI score with the standard ALBI score was 0.965 (P < 0.001). In multivariate analysis, factors including EZ-ALBI grade 2 and 3 were independently associated with increased mortality.

Study details: The data come from 3,794 patients newly diagnosed with HCC who were prospectively enrolled in the study and later analyzed.

Disclosures: The study was supported by the Taipei Veterans General Hospital. The researchers had no financial conflicts to disclose.  

Source: Ho S-Y et al. Hepatol Res. 2021 May 26. doi:10.1111/hepr.13671.

Key clinical point: The EZ albumin-bilirubin (ALBI) score was significantly correlated with the original and more complex ALBI score as a biomarker of liver injury.

Major finding: The correlation coefficient of the EZ-ALBI score with the standard ALBI score was 0.965 (P < 0.001). In multivariate analysis, factors including EZ-ALBI grade 2 and 3 were independently associated with increased mortality.

Study details: The data come from 3,794 patients newly diagnosed with HCC who were prospectively enrolled in the study and later analyzed.

Disclosures: The study was supported by the Taipei Veterans General Hospital. The researchers had no financial conflicts to disclose.  

Source: Ho S-Y et al. Hepatol Res. 2021 May 26. doi:10.1111/hepr.13671.

Key clinical point: The EZ albumin-bilirubin (ALBI) score was significantly correlated with the original and more complex ALBI score as a biomarker of liver injury.

Major finding: The correlation coefficient of the EZ-ALBI score with the standard ALBI score was 0.965 (P < 0.001). In multivariate analysis, factors including EZ-ALBI grade 2 and 3 were independently associated with increased mortality.

Study details: The data come from 3,794 patients newly diagnosed with HCC who were prospectively enrolled in the study and later analyzed.

Disclosures: The study was supported by the Taipei Veterans General Hospital. The researchers had no financial conflicts to disclose.  

Source: Ho S-Y et al. Hepatol Res. 2021 May 26. doi:10.1111/hepr.13671.

Key clinical point: Over a median follow-up of 36.7 months, safety and efficacy based on complications and rates of overall survival were not significantly different between hepatocellular carcinoma patients treated with radiofrequency ablation (RFA) and those treated with microwave ablation (MWA).

Major finding: Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%).

Study details: The data come from a retrospective study of 201 consecutive adult patients with hepatocellular carcinoma who underwent either radiofrequency ablation (150 patients) or microwave ablation (51 patients) at a single center between January 2012 and December 2016.

Disclosures: The study was supported by the Guangzhou Science and Technology Program and the Innovative Research Group Project of the National Natural Science Foundation of China.  The researchers had no financial conflicts to disclose.  

Source: Han X et al. Abdom Radiol. 2021 May 25. doi: 10.1007/s00261-021-03105-9.

Key clinical point: Over a median follow-up of 36.7 months, safety and efficacy based on complications and rates of overall survival were not significantly different between hepatocellular carcinoma patients treated with radiofrequency ablation (RFA) and those treated with microwave ablation (MWA).

Major finding: Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%).

Study details: The data come from a retrospective study of 201 consecutive adult patients with hepatocellular carcinoma who underwent either radiofrequency ablation (150 patients) or microwave ablation (51 patients) at a single center between January 2012 and December 2016.

Disclosures: The study was supported by the Guangzhou Science and Technology Program and the Innovative Research Group Project of the National Natural Science Foundation of China.  The researchers had no financial conflicts to disclose.  

Source: Han X et al. Abdom Radiol. 2021 May 25. doi: 10.1007/s00261-021-03105-9.

Key clinical point: Over a median follow-up of 36.7 months, safety and efficacy based on complications and rates of overall survival were not significantly different between hepatocellular carcinoma patients treated with radiofrequency ablation (RFA) and those treated with microwave ablation (MWA).

Major finding: Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%).

Study details: The data come from a retrospective study of 201 consecutive adult patients with hepatocellular carcinoma who underwent either radiofrequency ablation (150 patients) or microwave ablation (51 patients) at a single center between January 2012 and December 2016.

Disclosures: The study was supported by the Guangzhou Science and Technology Program and the Innovative Research Group Project of the National Natural Science Foundation of China.  The researchers had no financial conflicts to disclose.  

Source: Han X et al. Abdom Radiol. 2021 May 25. doi: 10.1007/s00261-021-03105-9.

First is an article from Elshaarawy O et al. who looked at preoperative and postoperative models to evaluate postresection survival. Between December 2010 and January 2017, 120 patients who underwent resection with curative intent, were analyzed for survival, liver decompensation, and posthepatectomy liver failure (PHLF). It will come as no surprise that HCC recurrence following resection adversely affected survival (hazard ratio (HR) = 11.67, 95%CI: 4.19-32.52, P < 0.001). Also affecting survival were the preoperative MELD score [HR = 1.37, 95%CI: 1.16-1.62, P < 0.001] and grades A through C of the PHLF score. Significant independent predictors of postoperative liver decompensation were the preoperative MELD score >10 [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter >5 cm (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (6. 8 days vs 11.26 days; OR = 2.5, 95%CI: 1.5-4.2, P = 0.001).

Next, Lei GY et al. undertook a retrospective study of 244 patients with HCC who underwent hepatic resection with curative intent between January 200 and December 2017. They found that the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. In these patients, the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%.

Taken together, these studies confirm that underlying liver function both before and after surgery is a key predictor of how well a patient is likely to do after curative-intent surgery. Excellent multidisciplinary care remains important for patient well-being.

Finally, for patients who are not candidates for liver resection, Han X et al. evaluated the efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) in a retrospective study of 201 consecutive patients whose tumors were within Milan criteria, but were in challenging locations for resection. RFA was performed in 150 patients, while 51 patients underwent MWA between January 2012 and December 2016.  Median follow-up was 36.7 months. Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%). The authors concluded that both procedures are equally safe and effective in patients with HCC.

First is an article from Elshaarawy O et al. who looked at preoperative and postoperative models to evaluate postresection survival. Between December 2010 and January 2017, 120 patients who underwent resection with curative intent, were analyzed for survival, liver decompensation, and posthepatectomy liver failure (PHLF). It will come as no surprise that HCC recurrence following resection adversely affected survival (hazard ratio (HR) = 11.67, 95%CI: 4.19-32.52, P < 0.001). Also affecting survival were the preoperative MELD score [HR = 1.37, 95%CI: 1.16-1.62, P < 0.001] and grades A through C of the PHLF score. Significant independent predictors of postoperative liver decompensation were the preoperative MELD score >10 [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter >5 cm (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (6. 8 days vs 11.26 days; OR = 2.5, 95%CI: 1.5-4.2, P = 0.001).

Next, Lei GY et al. undertook a retrospective study of 244 patients with HCC who underwent hepatic resection with curative intent between January 200 and December 2017. They found that the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. In these patients, the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%.

Taken together, these studies confirm that underlying liver function both before and after surgery is a key predictor of how well a patient is likely to do after curative-intent surgery. Excellent multidisciplinary care remains important for patient well-being.

Finally, for patients who are not candidates for liver resection, Han X et al. evaluated the efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) in a retrospective study of 201 consecutive patients whose tumors were within Milan criteria, but were in challenging locations for resection. RFA was performed in 150 patients, while 51 patients underwent MWA between January 2012 and December 2016.  Median follow-up was 36.7 months. Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%). The authors concluded that both procedures are equally safe and effective in patients with HCC.

First is an article from Elshaarawy O et al. who looked at preoperative and postoperative models to evaluate postresection survival. Between December 2010 and January 2017, 120 patients who underwent resection with curative intent, were analyzed for survival, liver decompensation, and posthepatectomy liver failure (PHLF). It will come as no surprise that HCC recurrence following resection adversely affected survival (hazard ratio (HR) = 11.67, 95%CI: 4.19-32.52, P < 0.001). Also affecting survival were the preoperative MELD score [HR = 1.37, 95%CI: 1.16-1.62, P < 0.001] and grades A through C of the PHLF score. Significant independent predictors of postoperative liver decompensation were the preoperative MELD score >10 [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter >5 cm (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (6. 8 days vs 11.26 days; OR = 2.5, 95%CI: 1.5-4.2, P = 0.001).

Next, Lei GY et al. undertook a retrospective study of 244 patients with HCC who underwent hepatic resection with curative intent between January 200 and December 2017. They found that the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. In these patients, the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%.

Taken together, these studies confirm that underlying liver function both before and after surgery is a key predictor of how well a patient is likely to do after curative-intent surgery. Excellent multidisciplinary care remains important for patient well-being.

Finally, for patients who are not candidates for liver resection, Han X et al. evaluated the efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) in a retrospective study of 201 consecutive patients whose tumors were within Milan criteria, but were in challenging locations for resection. RFA was performed in 150 patients, while 51 patients underwent MWA between January 2012 and December 2016.  Median follow-up was 36.7 months. Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%). The authors concluded that both procedures are equally safe and effective in patients with HCC.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

[email protected]

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

[email protected]

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

[email protected]

Medicare exacts a penalty whenever it deems that hospitals have too many patients with chronic obstructive pulmonary disease who have been re-admitted within 30 days of discharge for care related to the disease. For acute-care hospitals the solution to reducing chronic obstructive pulmonary disease (COPD) re-admissions has been elusive, but members of a COPD chronic care management collaborative think they have found at least a partial solution.

Among 33 centers participating in the performance improvement program, the aggregated cost avoidance for emergency department (ED) visits was estimated at $351,000, and the savings for hospital re-visits avoided was an estimated $2.6 million, reported Valerie Press, MD, MPH, from the University of Chicago, and co-authors from the health care performance-improvement company Vizient.

The investigators described their chronic care management collaborative in a thematic poster presented during the American Thoracic Society’s virtual international conference (Abstract A1688).

“I’ve been working in the space of COPD re-admissions pretty much since Medicare started its penalty program,” Dr. Press said in an interview.

“At both my own institution and nationally, we’ve been trying to understand the policy that went into place to reduce what was considered to be excessive readmissions after a COPD admission, but there really wasn’t a lot of evidence to suggest how to do this at the time the policy went into place,” she said.

The Centers for Medicare & Medicaid Services (CMS) initiated its Hospital Readmission Reduction Program for COPD in 2014.

“The challenge with COPD is that we have not found really successful interventions to decrease readmissions,” commented Laura C. Myers, MD, MPH, in an interview. Dr. Myers, who studies optimal care delivery models for patients with COPD at Kaiser Permanente Northern California in Oakland, was not involved in the study.

She said that although the aggregate cost savings in the study by Dr. Press and colleagues are relatively modest, “if you extrapolate across the country, then those numbers could potentially be impressive.”
 

Collaboration details

Dr. Press was a subject matter expert for the collaborative, which included 47 Vizient member sites in the Southeast, Southwest, Midwest, and Northeast and Northwest coasts. Of these centers, 33 completed both parts of the collaboration.

The program included bi-monthly didactic sessions and site report and discussion sessions with peer-to-peer networking for a total of 6 months. During the sessions, meeting participants discussed best practices, received expert coaching, and provided progress updates on performance improvement projects.

“The goal was for them to identify the gaps or needs they had at their hospitals or practices, and then to try to put in place one or more interventions,” Dr. Press said. “This wasn’t a research program. It wasn’t standardized, and not all hospitals had to do the same program.”

The participants submitted reports for baseline and post-collaboration periods on both an intervention’s “reach,” defined as the percentage of patients who received a specified intervention, and on two outcome measures.

The interventions measured included spirometry, follow-up visits scheduled within 7 to 14 days of discharge, patients receiving COPD education, pulmonary referrals, and adherence to the COPD clinical pathway.

The outcome measures were the rate of COPD-related ED visits and hospital readmissions.
 

Revisits reduced

At the end of the program, 83% of participating sites had reductions in either ED visits or readmissions, and of this group, five sites had decreases in both measures.

Among all sites with improved metrics, the average rate of COPD-related ED revisits declined from 12.7% to 9%, and average inpatient readmissions declined from 20.1% to 15.6%.

As noted, the estimated cost savings in ED revisits avoided was $351,00, and the estimated savings in hospital readmission costs was $2.6 million.

“Although the centers didn’t have to participate in both parts, we did see in our results that the programs that participated fully had better results,” Dr. Press said.

“Historically, we’ve had such difficulty in decreasing COPD readmissions, and it’s nice to see something that actually works, both for patients and for conserving health resources,” Dr. Myers commented.

The study was supported by Vizient. Dr. Press disclosed honoraria from the company in her role as subject matter expert. Dr. Myers reported no conflicts of interest.

Medicare exacts a penalty whenever it deems that hospitals have too many patients with chronic obstructive pulmonary disease who have been re-admitted within 30 days of discharge for care related to the disease. For acute-care hospitals the solution to reducing chronic obstructive pulmonary disease (COPD) re-admissions has been elusive, but members of a COPD chronic care management collaborative think they have found at least a partial solution.

Among 33 centers participating in the performance improvement program, the aggregated cost avoidance for emergency department (ED) visits was estimated at $351,000, and the savings for hospital re-visits avoided was an estimated $2.6 million, reported Valerie Press, MD, MPH, from the University of Chicago, and co-authors from the health care performance-improvement company Vizient.

The investigators described their chronic care management collaborative in a thematic poster presented during the American Thoracic Society’s virtual international conference (Abstract A1688).

“I’ve been working in the space of COPD re-admissions pretty much since Medicare started its penalty program,” Dr. Press said in an interview.

“At both my own institution and nationally, we’ve been trying to understand the policy that went into place to reduce what was considered to be excessive readmissions after a COPD admission, but there really wasn’t a lot of evidence to suggest how to do this at the time the policy went into place,” she said.

The Centers for Medicare & Medicaid Services (CMS) initiated its Hospital Readmission Reduction Program for COPD in 2014.

“The challenge with COPD is that we have not found really successful interventions to decrease readmissions,” commented Laura C. Myers, MD, MPH, in an interview. Dr. Myers, who studies optimal care delivery models for patients with COPD at Kaiser Permanente Northern California in Oakland, was not involved in the study.

She said that although the aggregate cost savings in the study by Dr. Press and colleagues are relatively modest, “if you extrapolate across the country, then those numbers could potentially be impressive.”
 

Collaboration details

Dr. Press was a subject matter expert for the collaborative, which included 47 Vizient member sites in the Southeast, Southwest, Midwest, and Northeast and Northwest coasts. Of these centers, 33 completed both parts of the collaboration.

The program included bi-monthly didactic sessions and site report and discussion sessions with peer-to-peer networking for a total of 6 months. During the sessions, meeting participants discussed best practices, received expert coaching, and provided progress updates on performance improvement projects.

“The goal was for them to identify the gaps or needs they had at their hospitals or practices, and then to try to put in place one or more interventions,” Dr. Press said. “This wasn’t a research program. It wasn’t standardized, and not all hospitals had to do the same program.”

The participants submitted reports for baseline and post-collaboration periods on both an intervention’s “reach,” defined as the percentage of patients who received a specified intervention, and on two outcome measures.

The interventions measured included spirometry, follow-up visits scheduled within 7 to 14 days of discharge, patients receiving COPD education, pulmonary referrals, and adherence to the COPD clinical pathway.

The outcome measures were the rate of COPD-related ED visits and hospital readmissions.
 

Revisits reduced

At the end of the program, 83% of participating sites had reductions in either ED visits or readmissions, and of this group, five sites had decreases in both measures.

Among all sites with improved metrics, the average rate of COPD-related ED revisits declined from 12.7% to 9%, and average inpatient readmissions declined from 20.1% to 15.6%.

As noted, the estimated cost savings in ED revisits avoided was $351,00, and the estimated savings in hospital readmission costs was $2.6 million.

“Although the centers didn’t have to participate in both parts, we did see in our results that the programs that participated fully had better results,” Dr. Press said.

“Historically, we’ve had such difficulty in decreasing COPD readmissions, and it’s nice to see something that actually works, both for patients and for conserving health resources,” Dr. Myers commented.

The study was supported by Vizient. Dr. Press disclosed honoraria from the company in her role as subject matter expert. Dr. Myers reported no conflicts of interest.

Medicare exacts a penalty whenever it deems that hospitals have too many patients with chronic obstructive pulmonary disease who have been re-admitted within 30 days of discharge for care related to the disease. For acute-care hospitals the solution to reducing chronic obstructive pulmonary disease (COPD) re-admissions has been elusive, but members of a COPD chronic care management collaborative think they have found at least a partial solution.

Among 33 centers participating in the performance improvement program, the aggregated cost avoidance for emergency department (ED) visits was estimated at $351,000, and the savings for hospital re-visits avoided was an estimated $2.6 million, reported Valerie Press, MD, MPH, from the University of Chicago, and co-authors from the health care performance-improvement company Vizient.

The investigators described their chronic care management collaborative in a thematic poster presented during the American Thoracic Society’s virtual international conference (Abstract A1688).

“I’ve been working in the space of COPD re-admissions pretty much since Medicare started its penalty program,” Dr. Press said in an interview.

“At both my own institution and nationally, we’ve been trying to understand the policy that went into place to reduce what was considered to be excessive readmissions after a COPD admission, but there really wasn’t a lot of evidence to suggest how to do this at the time the policy went into place,” she said.

The Centers for Medicare & Medicaid Services (CMS) initiated its Hospital Readmission Reduction Program for COPD in 2014.

“The challenge with COPD is that we have not found really successful interventions to decrease readmissions,” commented Laura C. Myers, MD, MPH, in an interview. Dr. Myers, who studies optimal care delivery models for patients with COPD at Kaiser Permanente Northern California in Oakland, was not involved in the study.

She said that although the aggregate cost savings in the study by Dr. Press and colleagues are relatively modest, “if you extrapolate across the country, then those numbers could potentially be impressive.”
 

Collaboration details

Dr. Press was a subject matter expert for the collaborative, which included 47 Vizient member sites in the Southeast, Southwest, Midwest, and Northeast and Northwest coasts. Of these centers, 33 completed both parts of the collaboration.

The program included bi-monthly didactic sessions and site report and discussion sessions with peer-to-peer networking for a total of 6 months. During the sessions, meeting participants discussed best practices, received expert coaching, and provided progress updates on performance improvement projects.

“The goal was for them to identify the gaps or needs they had at their hospitals or practices, and then to try to put in place one or more interventions,” Dr. Press said. “This wasn’t a research program. It wasn’t standardized, and not all hospitals had to do the same program.”

The participants submitted reports for baseline and post-collaboration periods on both an intervention’s “reach,” defined as the percentage of patients who received a specified intervention, and on two outcome measures.

The interventions measured included spirometry, follow-up visits scheduled within 7 to 14 days of discharge, patients receiving COPD education, pulmonary referrals, and adherence to the COPD clinical pathway.

The outcome measures were the rate of COPD-related ED visits and hospital readmissions.
 

Revisits reduced

At the end of the program, 83% of participating sites had reductions in either ED visits or readmissions, and of this group, five sites had decreases in both measures.

Among all sites with improved metrics, the average rate of COPD-related ED revisits declined from 12.7% to 9%, and average inpatient readmissions declined from 20.1% to 15.6%.

As noted, the estimated cost savings in ED revisits avoided was $351,00, and the estimated savings in hospital readmission costs was $2.6 million.

“Although the centers didn’t have to participate in both parts, we did see in our results that the programs that participated fully had better results,” Dr. Press said.

“Historically, we’ve had such difficulty in decreasing COPD readmissions, and it’s nice to see something that actually works, both for patients and for conserving health resources,” Dr. Myers commented.

The study was supported by Vizient. Dr. Press disclosed honoraria from the company in her role as subject matter expert. Dr. Myers reported no conflicts of interest.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.