Sacituzumab govitecan, an antibody drug conjugate, maintained progression-free survival (PFS), overall survival (OS), and response benefits over chemotherapy regimens, regardless of the agents used, according to data from a subanalysis of the phase 3 ASCENT trial (NCT02574455), presented during the 2021 ASCO Annual Meeting.

Sacituzumab govitecan resulted in a longer median PFS compared with any of the physician’s choice chemotherapy options, which included eribulin, vinorelbine, capecitabine, or gemcitabine (HR, 0.41; 95% CI, 0.32-0.52; 

 <.001). The median PFS, by blinded independent central review, was 5.6 months (95% CI, 4.3-6.3) with the ADC, 2.1 months (95% CI, 1.5-2.8) with eribulin, 1.6 months (95% CI, 1.4-2.7) with vinorelbine, 1.6 months (95% CI, 1.4-2.4) with capecitabine, and 2.7 months (95% CI, 1.6-4.8) with gemcitabine.

The ADC also prolonged the median OS over eribulin, vinorelbine, capecitabine, or gemcitabine, at 12.1 months (95% CI, 10.7-14.0) vs 6.9 months (95% CI, 5.8-7.8), 5.9 months (95% CI, 4.5-6.7), 5.2 months (95% CI, 3.5-8.6), and 8.4 months (95% CI, 5.0-9.6), respectively (HR, 0.48; 95% CI, 0.38-0.59; 

 <.001). Sacituzumab govitecan elicited an ORR of 35% vs 5%, 4%, 6%, and 3% with eribulin, vinorelbine, capecitabine, or gemcitabine, respectively.

“The efficacy benefit for median PFS, median OS, and ORR with sacituzumab govitecan vs single-agent chemotherapy in the second-line or greater metastatic TNBC setting in ASCENT was retained when evaluating each chemotherapy agent individually,” Joyce A. O’Shaughnessy, MD, lead study author, cochair of Breast Cancer Research and chair of breast cancer prevention research at Baylor-Sammons Cancer Center of Texas Oncology, said in a poster presentation on the data. “These results confirm that sacituzumab govitecan should be considered as a new standard of care in this patient population.”

For patients with previously treated TNBC, standard treatment has comprised single-agent chemotherapy; however, this approach has been linked with responses rates of under 20% and a short PFS ranging from just 2 to 3 months. Eribulin is a frequently used agent in this population, but median PFS continues to be poor, at less than 3 months.

Sacituzumab govitecan is comprised of a Trop-2 antibody that is paired with SN-38 through a proprietary hydrolysable linker. The agent is unique from other available ADCs in that the antibody is highly specific for Trop-2 and it has a high drug-to-antibody ratio of 7:6:1. Moreover, internalization and enzymatic cleavage by tumor cell is not needed to free SN-38 from the antibody. Notably, the ADC also has a bystander effect because hydrolysis of the linker releases SN-38 extracellularly in the tumor microenvironment.

In April 2021, the FDA granted a full approval to sacituzumab govitecan for the treatment of patients with unresectable locally advanced or metastatic TNBC who have received 2 or more prior systemic therapies, at least 1 of them for metastatic disease. The regulatory decision was based on earlier data from ASCENT, which showed that the agent significantly improved survival over physician’s choice of single-agent chemotherapy in patients with metastatic TNBC who were receiving treatment in the second- or later-line setting.

Earlier data from the trial showed that the median PFS with the ADC was 5.6 months (95% CI, 4.3-6.3) vs 1.7 months (95% CI, 1.5-2.6) with chemotherapy (HR, 0.41; 95% CI, 0.32-0.52; 

 <.001). Moreover, the median OS in the investigative and control arms was 12.1 months (95% CI, 10.7-14.0) and 6.7 months (95% CI, 5.8-7.7), respectively (HR, 0.48; 95% CI, 0.38-0.59; 

In the subanalysis presented during the meeting, investigators evaluated the safety and efficacy of sacituzumab govitecan vs each chemotherapy agent to determine how each drug performed individually.

Of the 529 patients enrolled to the phase 3 study, 235 patients in the ADC arm were negative from brain metastases, as were 233 patients in the chemotherapy arm. In the control arm, eribulin was noted to be the most frequently selected agent (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29).

At the time of data cutoff, 6% (n = 15) of those on the sacituzumab govitecan arm remained on treatment vs 0% of those on the chemotherapy arm. The most frequently reported reasons for study discontinuation included disease progression and withdrawn consent.

Across the arms, the majority of patients were female, and the median age ranged from 50 years to 56 years. The majority of patients were White, had an ECOG performance status of 1, and received more than 3 prior lines of chemotherapy. The median number of prior anticancer regimens received ranged from 3 to 5 lines.

Additional data showed that of those who responded to treatment with sacituzumab govitecan, the complete response (CR) rate was 4% and the partial response (PR) rate was 31%. The clinical benefit rate achieved with the ADC was 45% vs 8% with eribulin, 6% with vinorelbine, 10% with capecitabine, and 14% with gemcitabine. The median duration of response across these subsets was 6.3 months (95% CI, 5.5-9.0), 3.6 months (95% CI, 2.9-4.2), 2.8 months (not evaluable [NE]), NE, and 2.9 months (NE), respectively.

Regarding safety, key treatment-related adverse effects (TRAEs) that were grade 3 or higher in severity experienced with the ADC vs eribulin comprised neutropenia (51% vs 31%), leukopenia (10% vs 5%), diarrhea (10% vs 0%), anemia (8% vs 2%), febrile neutropenia (6% vs 2%), fatigue (3% vs 5%), and peripheral neuropathy (0% vs 2%).

Important grade 3 or higher TRAEs reported with sacituzumab govitecan vs vinorelbine, capecitabine, and gemcitabine combined included neutropenia (51% vs 36%), leukopenia (10% vs 6%), diarrhea (10% vs 1%), anemia (8% vs 8%), febrile neutropenia (6% vs 2%), and fatigue (3% vs 6%).

Additionally, treatment-emergent AEs resulted in discontinuation in 5% of those who received sacituzumab govitecan, 2% of those given eribulin, 10% of those who received vinorelbine, 7% of those given capecitabine, and 9% of those who were administered gemcitabine. Only 1 treatment-related death was reported in the chemotherapy arm; this patient received eribulin and had died from neutropenia sepsis. Notably, no treatment-related deaths occurred with the ADC.

“The safety profile of sacituzumab govitecan vs single-agent chemotherapy in the second-line or greater metastatic TNBC setting in ASCENT was comparable,” O’Shaughnessy concluded.

O’Shaughnessy J, Punie K, Oliveira M, et al. Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC). 

. 2021;39(suppl 15):1077. doi:10.1200/JCO.2021.39.15_suppl.1077

Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. 

. 2021;384(16):1529-1541. doi:10.1056/NEJMoa2028485

Articles

Sacituzumab govitecan, an antibody drug conjugate, maintained survival and response benefits over chemotherapy regimens.

Sacituzumab Govitecan Beats All Chemo Regimens in TNBC Treatment

Patients with BRCA1/2-mutant, early HER2-negative breast cancer at a high risk of recurrence saw a clinically meaningful benefit 1 year after standard of care when treated with olaparib (Lynparza), according to data from the phase 3 OlympiA trial (NCT02032823).

Results from the multicenter, randomized, placebo-controlled trial, which were presented during a virtual press briefing ahead of the 

 indicated that after a median follow-up of 2.5 years, patients who received olaparib experienced a 42% reduction in invasive disease-free survival (iDFS), including local and metastatic recurrence of breast cancer, other new cancers, and death due to any cause, (Hazard ratio [HR], 0.58; 99.5% CI, 0.41-0.82; 

 <.0001). Additionally, investigators noted a difference in 3-year iDFS rate between olaparib and placebo of 8.8% (95% CI, 4.5%-13.0%; stratified HR, 0.58; 99.5% CI, 0.41-0.82; 

“The OlympiA study is the first to report the benefits of [an adjuvant] PARP inhibitor for early forms of germline 

–mutation associated cancer,” presenting study author Andrew Tutt, MB, ChB, PhD, FMedSci, head of the Division of Breast Cancer Research, director of the Breast Cancer Now Toby Robins Research Centre, a clinician scientist with the Laboratory and Clinical Trials programme, and consultant clinical oncologist at the Institute of Cancer Research, said. “Patients who received olaparib after surgery and chemotherapy were more likely to be alive without cancer, [as well as] avoid metastasis than the patients who received placebo.”

Patients with HER2-negative early breast cancer who harbor a 

 mutation, which are present in approximately 5% of all breast cancers, are at a high risk of disease recurrence. Although outcomes have been positive for patients with these mutations who have received standard treatments such as surgery, radiotherapy, and chemotherapy, the risk of recurrence remains high for some patients. As such, additional novel targeted therapies are needed in order to reduce the risk of recurrence in this patient population.

Olaparib is a PARP inhibitor that targets DNA repair defects in certain germline-mutant cancers and was previously approved by the FDA in January 2018 for the treatment of patients with germline BRCA-positive, HER2-negative metastatic breast cancer. As such, investigators sought to examine the agent in patients with germline 

–mutated, HER2-negative early breast cancer.

The trial enrolled 1836 patients with HER2-negative breast cancer harboring a germline 

 mutation who were randomized 1:1 to receive either 300 mg of oral olaparib (n = 921) twice daily for 1 year or placebo (n = 915). Additionally, patients needed to have been treated for early stage (stage II-III) breast cancer and have completed surgery and chemotherapy, with or without radiotherapy. Inclusion criteria also required that patients have a high risk of disease recurrence. Those who had received prior treatment with a PARP inhibitor were not eligible to enroll.

The primary end point for the study was iDFS, while secondary end points included distant disease-free survival (DDFS), overall survival (OS), health-related quality of life, and safety.

“Stringent criteria were applied for a planned interim analysis,” Tutt said. “At this analysis, OlympiA’s Independent Data Monitoring Committee found [that] these stringent criteria were met for early reporting.”

Additional findings indicated that after a median follow-up of 2.5 years, patients who were treated with olaparib experienced a 43% reduction in DDFS, including metastatic disease, new cancer, and death due to any cause (HR, 0.57; 99.5% CI, 0.39-0.83; 

 <.0001). The difference in 3-year DDFS rate between olaparib and placebo was 7.1% (95% CI, 3.0%-11.1%; stratified HR, 0.57; 99.5%, 0.39-0.83; 

At the time of the early primary end point report, OS data were considered immature. However, while fewer deaths were reported in patients receiving olaparib vs placebo, OS was not significantly different between the 2 study cohorts at a median follow up of 2.5 years(HR, 0.68; 99% CI, 0.44-1.05; 

 = .024). Moreover, the difference in 3-year OS rate between the 2 arms was 3.7% (95% CI, 0.3%-7.1%).

In terms of the safety profile, the adverse effects (AEs) reported in the olaparib group were consistent with what has been previously reported with the agent. Additionally, Olaparib did not increase serious AEs, including hospital admissions or occurrences of other cancers such as leukemia. However, grade 3 or higher AEs were reported more often in patients receiving treatment with olaparib, and included anemia (9%), neutropenia (5%), leukopenia (3%), and fatigue (2%).

The most common AEs of any grade reported in patients who received olaparib included nausea (57%), fatigue (40%), anemia (23%), vomiting (23%), and headache (20%). Moreover, the most common any grade AEs in the placebo arm were fatigue (27%), nausea (23%), headache (17%), diarrhea (14%), and arthralgia (12%).

1. Tutt A, Garber J, Kaufman B, et al. OlympiA: a phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer. Presented at: 2021 ASCO Annual Meeting; June 4-8, 2021; Virtual. Abstract LBA1

2. Olaparib as adjuvant treatment in patients with germline BRCA mutated high risk HER2 negative primary breast cancer (OlympiA). ClinicalTrials.gov. Updated March 9, 2021. Accessed June 2, 2021. 

https://clinicaltrials.gov/ct2/show/NCT02032823

Patients with BRCA1/2-mutant, early HER2-negative breast cancer at a high risk of recurrence saw a clinically meaningful benefit 1 year after standard of care when treated with olaparib.

Olaparib Is Beneficial 1 Year After Standard of Care Therapies in BRCA, High-Risk, Early HER2- Breast Cancer

Screenings for breast cancer, colorectal cancer (CRC), and prostate cancer declined sharply from March to May 2020 vs the same time span in 2019, suggesting that public health efforts, such as increased use of screening modalities that do not require a procedure, are needed to address the deficit caused by the COVID-19 pandemic, according to findings from a study that were published in 

Within the 3-month period in 2020, the sharpest decline in screening for breast cancer, CRC, and prostate cancer was observed in April 2020 compared with the same month in 2019; screenings declined by 90.8%, 79.3%, and 63.4% in breast cancer, CRC, and prostate cancer, respectively.

Compared with April 2019, the incidence of breast cancer screenings in April 2020 declined from 4287 per 100,000 individuals (95% CI, 4258-4316) to 394 per 100,000 individuals (95% CI, 385-403). The incidence of CRC screenings declined from 2073 per 100,000 individuals (95% CI, 2058-2087) to 430 per 100,000 individuals (95% CI, 423-436). The incidence of prostate cancer screenings declined from 4025 per 100,000 individuals (95% CI, 3993-4057) to 1474 per 100,000 individuals (95% CI, 1454-1493).

Notably, near complete recovery in monthly screening rates were observed by July 2020 for patients with breast cancer and prostate cancer.

"Unfortunately, by causing cancellations of appointments and cancer screenings, COVID will indirectly cause an increase in cancer deaths—another negative consequence of COVID that has not yet received much public attention," said lead study author Ronald C. Chen, MD, MPH, the Joe and Jean Brandmeyer Endowed Chair in the Department of Radiation Oncology at the University of Kansas Medical Center.

The COVID-19 pandemic significantly affected all elements of health care, including cancer treatment and screening, across the United States in 2020, Chen and co-authors wrote.1 Stay-at-home orders and safety guidelines issued by the CDC to minimize COVID-19 transmission resulted in a significant decline in non-emergency clinical visits, particularly among older, high-risk patients, explained Chen and co-authors.

The study evaluated 3 distinct cohorts of patients from the HealthCore Integrated Research Database, which comprises single-payer administrative claims data and enrollment information from about 60 million patients in Medicare Advantage and commercial insurance plans across the United States. The cohorts included women with breast cancer, men and women with CRC, and men with prostate cancer.

Cancer screenings were evaluated from 2018 to 2020. Evaluable individuals for breast cancer screening or CRC screening were aged 50 to 79 years, and evaluable individuals for prostate cancer screening were aged 50 to 69 years. Individuals had to have at least 2 years of continuous enrollment before the first day of the index month. Restrictions based on medical claims and personal history codes for cancers of interest further refined the evaluable population.

“Excluding individuals with a history of the cancer of interest allowed us to more accurately assess cancer screening,” wrote Chen and co-authors.

Additional results from the study revealed that despite the rebound in monthly cancer screening rates, a deficit in total cancer screenings from January to July 2020 remained compared with January to July 2019. This translated to a United States–population deficit in breast cancer, CRC, and prostate cancer screenings of approximately 3.9 million women, 3.8 million men and women, and 1.6 million men, respectively. Moreover, the total deficit in cancer screenings was estimated at 9.4 million individuals in 2020 compared with 2019.

By geographic region, the Northeastern United States reported the sharpest decline in cancer screenings in March, April, and May for all 3 cancer types. The Western region had a slower recovery in screening during June and July compared with the Midwest and South regions.

Regarding socioeconomic status, prior to the pandemic, screening rates were higher for all 3 cancer types in the highest 2 socioeconomic index quartiles compared with the lower 2 socioeconomic index quartiles. However, the highest socioeconomic index quartile reported the largest decline in screening for all 3 cancer types from January to July 2020 compared with the same period in 2019. Moreover, the decline narrowed the gap in screening rates across the quartiles in 2020 vs 2019.

Other key findings from the study showed that increasing age was associated with less screening in all 3 cancer types. Individuals in the higher quartiles were screened less for breast cancer and CRC in April 2020 compared with individuals in the lower quartiles.

Notably, individuals who utilized telemedicine services had higher rates of cancer screening across the 3 cancer types evaluated.

“Telehealth has a measurable positive effect on whether patients get their cancer screenings,” Chen said.2 “This study also justifies a continued use of telehealth even after the pandemic.”

Chen and co-authors reported that analyzing only insured individuals, the lack of racial/ethnic diversity in the study population, the use of nonspecific codes for screening, and the inclusion of individuals without a history of cancer were limitations of the study.

“As a physician, I wasn’t surprised to see that screenings had declined, but this study measures by how much. There needs to be a concerted public health educational campaign across the country to reinforce the importance of cancer screening. Hospitals across the country also need to devote effort to contact patients to reschedule canceled screening tests, in order to minimize the delay in screening and cancer diagnoses from the missed tests,” concluded Chen.2

Chen RC, Haynes K, Du S, et al. Association of cancer screening deficit in the United States with the COVID-19 pandemic. 

. Published online April 29, 2021. Accessed May 13, 2021. doi:10.1001/jamaoncol.2021.0884

Massive negative impact of COVID-19 on cancer screenings quantified in KU Medical Center faculty study published in JAMA Oncology. News release. April 29, 2021. Accessed May 13, 2021. https://bit.ly/3ojB2fJ.

This article was originally published on OncLive as, "

Routine Screening Rates for Breast, Colorectal, and Prostate Cancers Decline During COVID-19 Pandemic

Public health efforts must address new methods of cancer screening, an expert says.

Routine Cancer Screening Declined During the COVID-19 Pandemic

Updated survival data from the phase 3 Short-HER trial (NCT00629278) presented during the ESMO Breast Cancer Virtual Congress 2021 confirm the promising long-term results obtained with 9 weeks of adjuvant trastuzumab (Herceptin) in patients with HER2-positive early breast cancer who have low and intermediate risk factors, a population that is representative of most patients seen in clinical practice.

After a median follow-up of 8.7 years, patients who received 1 year of trastuzumab had a 5-year disease-free survival (DFS) rate of 87.9% vs 85.8% those who received it for 9 weeks (hazard ratio [HR], 1.09; 90% CI, 0.88-1.35). Moreover, patients had a 5-year overall survival (OS) rate of 95.1% in both arms, respectively (HR, 1.18; 90% CI, 0.86-1.62).

“Patients classified as low/intermediate risk on the basis of [tumor] size and nodal status represent 84.6% of the Short-HER study population. In this patient population, long-term DFS and OS are superimposable between the 2 treatment arms,” Pier Franco Conte, MD, a full professor of oncology at the University of Padova, Italy; director of the Division of Medical Oncology at the Istituto Oncologico Veneto in Padova; and chairman of Rete Oncologica Veneta, said in a presentation on the findings. “Although 1 year of trastuzumab remains a standard, de-escalation of treatment is a reasonable option for a large proportion of a real-world population of [patients with] HER2-positive early breast cancer.”

The superiority of combining 1 year of trastuzumab with adjuvant chemotherapy over chemotherapy alone in patients with HER2-positive early breast cancer was demonstrated in the phase 3 HERA (NCT00045032), Joint Analysis B31-N9831, and N9831 trials.

 In November 2006, trastuzumab was approved by the FDA as an adjuvant therapy for patients with HER2-positive, node-positive breast cancer as part of a treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel.

“It was very clear at the time that the choice of a 1-year duration of trastuzumab administration was based empirically and that a similar degree of benefit had already been reported with the small FinHER study with 9 weeks of trastuzumab,” Conte noted.

The Short-HER trial, which was an investigator-driven, noninferiority study, started off with an initial sample size of 2500 patients; however, as of February 2011, this was amended to 1250 patients. The study was conducted across 82 investigational sites in Italy and had a recruitment period that ran from December 2007 to October 2013. The primary analysis was completed after 189 DFS events at 5.2 years median follow-up.

The trial enrolled patients with HER2-positive, node positive, or high-risk node-negative disease. “Patients were then randomized to receive either 1 year of trastuzumab plus chemotherapy, which included 4 courses of doxorubicin and cyclophosphamide, followed by 4 courses of a taxane, vs 3 courses of docetaxel combined with 9 weeks of weekly trastuzumab followed by 3 courses of fluorouracil, epirubicin hydrochloride, and cyclophosphamide,” Conte said. Stratification factors included hormone receptor status and nodal status. Patients who were aged 65 years or older received docetaxel at 80 mg/sqm dose of docetaxel. Eleven percent of patients who received the longer duration of trastuzumab were given paclitaxel at 175 mg/sqm.

The overall patient population had a median age of 55 years (range, 25-78), and 64.0% were postmenopausal. Moreover, 40.6% of patients had stage I disease, 43.8% had stage II disease, and 15.2% had stage III disease. Most patients were node negative (53.5%), although 30.7% of patients had 1 to 3 positive nodes and 15.8% had at least 4 positive nodes. Additionally, 68.2% of patients had hormone receptor–positive status.

The DFS reported in the primary analysis of the trial showcased a HR of 1.13 (90%, CI, 0.89-1.42). Investigators reported that the probability that the shorter duration of treatment would be noninferior to that of the longer duration was 78% .

 Moreover, the primary analysis identified an association between a longer duration of treatment and a longer and higher incidence of cardiac events. The incidence of grade 2 or higher cardiac events was 13.1% in the long-duration treatment arm vs 4.3% in the short-duration treatment arm.

The updated results of the study had a median follow-up of 8.7 years with 237 DFS events and 109 deaths.

Investigators also examined DFS and OS outcomes with respect to risk category. “The high-risk group clearly has worse outcomes in terms of both DFS and OS, while both low- and intermediate-risk groups had very good DFS and OS estimates,” Conte said.

Patients in the low-risk group experienced a 5-year DFS of 91% in both treatment arms (HR, 0.91). In the intermediate-risk group, those who were treated with the longer duration of treatment had a 5-year DFS rate of 88% vs 89% with the shorter duration (HR, 0.88); the 5-year DFS rates in the high-risk group for the longer and shorter treatment durations were 82% and 64%, respectively (HR, 2.06).

Additionally, the 5-year OS rate for patients in the low-risk group who received the longer duration of treatment was 97% vs 99% with the shorter duration (HR, 0.57). In the intermediate-risk group, these rates were 96% and 95%, respectively (HR, 1.14), while they were 95% ad 91%, respectively, in the high-risk group (HR, 1.09).

Conte P, Frassoldati A, Bisagni G, et al. Nine weeks vs 1 year adjuvant trastuzumab: long term outcomes of the Short-HER randomized trial. Presented at: ESMO Breast Cancer Virtual Congress 2021. May 5-8, 2021; Virtual. Abstract 401.

Herceptin (Trastuzumab) in treating women with human epidermal growth factor receptor (HER) 2-positive primary breast cancer (HERA). ClinicalTrials.org. Updated April 27, 2017. Accessed May 7, 2021. https://clinicaltrials.gov/ct2/show/NCT00045032

Doxorubicin and cyclophosphamide plus paclitaxel with or without trastuzumab in treating women with node-positive breast cancer that overexpresses HER2. ClinicalTrials.gov. Updated April 29, 2021. Accessed May 7, 2021. 

https://clinicaltrials.gov/ct2/show/NCT00004067

Doxorubicin hydrochloride, cyclophosphamide, and paclitaxel with or without trastuzumab in treating women with HER2-positive node-positive or high-risk node-negative breast cancer. ClinicalTrials.gov. Updated August 2020. Accessed May 7, 2021. 

https://clinicaltrials.gov/ct2/show/NCT00005970

FDA approves Herceptin for the adjuvant treatment of HER2-positive node-positive breast cancer. News release. FDA. November 16, 2006. Accessed May 7, 2021. 

Conte P, Bisagni G, Frassoldati A, et al. Final analysis of the phase III multicentric Italian study Short-HER: 9 weeks vs 1 year adjuvant trastuzumab for HER21 early breast cancer. 

. 2017;28(suppl 6):vi1-vi2. doi:10.1093/annonc/mdx421

Shorter Duration of Adjuvant Trastuzumab Shows Long-Term Survival Benefit in Select HER2+ Early Breast Cancer.

A 9-week trastuzumab regimen may be favorable for patients with HER2-positive early breast cancer who have low and intermediate risk factors. 

Shorter Adjuvant Trastuzumab Has Long-Term Benefits for HER2+ Breast Cancer

Post-treatment care for breast cancer survivors must be personalized to address each survivor’s unique experiences, according to a study presented at the ESMO Breast Cancer Virtual Congress 2021. Women in the low- and intermediate-burden subgroups had symptom scores better or equal to the average Dutch woman but many in the high-burden subgroup were significantly worse than average for all 11 symptoms evaluated.

The low subgroup reported a lower symptom burden compared to the general population. The intermediate subgroup experienced burden similar to the general population, although scores for fatigue, insomnia, and cognitive symptoms were slightly worse.

Symptom burden in the high subgroup was significantly than the general population. Compared with the intermediate subgroup, patients in the high burden group were more likely to have at least 1 comorbidity (relative risk ratio (RRR), 2.75; 95% CI, 1.22-6.19; 

 = .015) and more likely to have multiple comorbidities (RRR, 9.19; 95% CI; 3.70-22.8; 

“I was pleasantly surprised to find that so many survivors were doing as well or even better than the average Dutch woman,” lead author Kelly de Ligt, PhD, from the Netherlands Cancer Institute in Amsterdam, said in a news release.

de Ligt added that the findings in the high-burden subgroup were alarming. “This was the smallest group, only 15% of our population, but nonetheless, 1 in 6 women in our study had worse scores than the general population for all symptoms. The differences, ranging between 15 and 20 percentage points, were large enough to be considered not just statistically significant, but clinically relevant as well.”

More and more women are living longer following a diagnosis of breast cancer. The 10-year survival rate is greater than 70% in Europe and 84% for non-metastatic invasive disease in the United States.

 Quality of life is extremely important for these patients and de Ligt said these findings confirm the necessity for personalized approaches to the follow-up of cancer patients, some of whom still require special attention as long as 5 years after diagnosis.

de Ligt and her colleagues surveyed 404 women who received surgery with or without adjuvant treatment for stage I to III breast cancer selected from the Netherlands Cancer Registry. Participants were 1 to 5 years postdiagnosis and compared with a representative sample of 1300 women from the general population.

Investigators assessed participants for fatigue, nausea, pain, dyspnea, insomnia, appetite, constipation, diarrhea, financial burden, and emotional and cognitive symptoms on a scale 0-100 through the EORTC-QLQ-C30. Participants were then segregated into low- (28.7%), intermediate- (55.4%), and high-burden groups (14.6%) based on their responses.

de Ligt and her team also determined that patients with comorbidities such as heart disease and diabetes were more likely to experience a high symptom burden. de Ligt said the association was so strong that investigators could not connect the level of symptom burden with the type of therapy received.

“Future research should attempt to measure patients’ health-related quality of life through Patient Reported Outcome Measures (PROMs) before the start of treatment for breast cancer and afterwards to allow us to measure the effect of the therapy,” she said.

de Light KM, de Rooij BH, Walraven I, et al. Towards tailored follow-up care for breast cancer survivors: cluster analyses based on symptom burden. Presented at: ESMO Breast Cancer Virtual Congress 2021. Abst # 134P_PR. 

Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow up. 

Breast cancer: statistics. Cancer.net. January 2021. Accessed May 4, 2021. https://www.cancer.net/cancer-types/breast-cancer/statistics

Breast Cancer Survivors Need More Tailored Follow-Up Care

Each patient with breast cancer has a unique experience. Their survivorship care should reflect that.

Tailored Survivorship Care Is Needed in the Breast Cancer Space

It is well known that fear of recurrence is a major issue in the cancer community, but can genetic test results outlining risk impact those feelings?

For this episode of “The Vitals,” we spoke with Maurade Gormley, CPNP, RN, assistant professor and post-doctoral fellow at the NYU Rory Myers College of Nursing. Her recent research analyzed how Oncotype DX genomic test results may increase fear of recurrence in breast cancer survivors.

Podcasts

Genetic Testing May Increase Fear of Recurrence

Patients with breast cancer may benefit a rehabilitation program that provides guidance as they transition from active treatment to survivorship, according to a poster presentation at the 46th Annual ONS Congress.

“Patients often expressed feeling anxious and overwhelmed as they transition to survivorship. In addition, they noted decrease in support from their health care team. Therefore, our team created the breast cancer rehabilitation program to provide guidance and support to patients as they transition from active treatment to survivorship,” Laura Kaminski BSN, RN, OCN, a nurse navigator at INOVA Life with Cancer, said in a recording presented at the meeting.

The Breast Cancer Rehabilitation Program – led by a specialist team comprised of an oncology nurse navigator, physical therapist, oncology dietician, fitness instructor, and oncology clinical therapist – is a 6-week multidisciplinary series, with each week addressing a different survivorship topic.

“A multidisciplinary team is particularly valuable for addressing the variety of challenges that survivorship patients face,” Kaminski wrote in her poster.

Each specialist led sessions that focused on the following:

survivorship and surveillance with a nurse navigator

physical therapy, occupational therapy, and speech-language pathology’s roles in survivorship with a physical therapist

brain fog with an oncology clinical therapist

coping with survivorship’s emotional impact with an oncology clinical therapist

exercise guidelines for survivors with a fitness instructor

nutrition in survivorship with an oncology dietician.

To evaluate the effectiveness of the program, survivors completed a survey before and after the program. Before the program, patients, on average, rated their knowledge of survivorship topics as 3.2 on a 5-point scale. Post-survey responses showed that there was an increase in knowledge of all survivorship topics, with an average knowledge score of 4.7. Knowledge of survivorship/surveillance and brain fog were the topics of greatest improvement.

Kaminski noted that this program could offer similar education across various cancer types to contribute to improved survivorship outcomes.

INOVA Life with Cancer launched the program on January 14, 2020, and now offers it quarterly.

“Our organization plans to continue offering the breast cancer rehab program and has already made adjustments to the program based on patient feedback. For example, and 2021. A session was added to address sexual health and intimacy and survivorship,” Kaminski said.

Kaminski L. Breast Cancer Rehabilitation Program: Healing Mind, Body and Soul. Presented at: 46th Annual ONS Congress; April 20, 2021; virtual.

In particular, patients reported improved knowledge in survivorship/surveillance and brain fog following the 6-week program.

Survivorship Rehabilitation Program Provides Education to Improve Transition Following Active Treatment 

The coronavirus disease 2019 (COVID-19) pandemic had a tremendous impact on the surgical care of patients with breast cancer, according to Cindy Matsen, MD, who added that practice patterns needed to be rapidly adjusted to continue to safely provide care during a time when resources were very limited.

“When the COVID-19 pandemic hit our country, especially during March [2020], when we went into lockdown, we saw huge impacts on surgical care,” Matsen said. “We were anticipating a big surge of patients who would affect our system's capacity to be able to [manage] these patients. As such, we very quickly had to start triaging patients into different groups to understand who needed [surgery immediately] versus who could [have their procedures] delayed safely.”

® during an Institutional Perspective in Cancer webinar on Breast Cancer, Matsen, a breast surgeon and an assistant professor in the Department of Surgery at the Huntsman Cancer Institute, of the University of Utah, shared the protocols her institution put into place to ensure safe surgical practice for patients with breast cancer during the COVID-19 pandemic and how protective measures have evolved over the past year.

: What were some of the main challenges that arose during lockdown with regard to surgery in patients with breast cancer?

: The main challenge was that we were asked to cancel all surgeries very quickly; it all happened basically over a weekend. We got an email on Friday, saying, ‘Hey, we think that we're going to need to cancel all surgeries.’ As such, over that weekend, we had to come up with lists of who we could cancel versus who we could not. There still was some operating room availability [at that time], but it was much more limited than it had been.

A lot of phone calls [were being made], with both our patients and our clinic staff. We were trying to get everything worked out and deal with the psychological consequences of having to cancel [these procedures]. Everyone was reeling from the idea of a lockdown. We were all hoping that by shutting everything down, we were going to be able to truly flatten the curve and return to normal in about 4 to 6 weeks; that obviously didn't happen. However, it did allow us time to plan a little better for when the surge did actually happen.

At that time, we were also dealing with a scarcity of personal protective equipment [PPE], which was very concerning. This was something that really impacts surgery specifically, because we need to wear masks, gowns, and gloves [for those procedures]. If that equipment is not available, then we can't do surgery. [Our concerns went beyond] seeing a big surge and not having enough beds. [We were worried about] whether we would have the basic equipment available to us to be able to perform any sort of surgery.

[We also had to figure out] who to have in the operating room. All of a sudden, all our residents, all our students, everyone is gone. Even if you went to the operating room, it was a very limited team, which is very different from how this normally works for us.

You mentioned that a lot of important decision making happened via phone over that weekend. What did you discuss and what are some of the solutions you came up with?

We used those phone calls among our group to come up with some protocols for canceling all non–time sensitive surgery. Who is time sensitive and who is not? Receptor status, the type of surgery that was scheduled, and the phase of treatment were all factors we took into account to come up with a triage system for who would be most at risk for having bad outcomes if we delayed their surgery, and who we felt could safely be delayed with strategies like neoadjuvant endocrine therapy.

That was probably the biggest shift: patients with estrogen receptor–positive, HER2-negative, early-stage disease, who would normally go to surgery first [turned to] other options. We're lucky in breast cancer that we have other options for these patients. Many received neoadjuvant endocrine therapy during that time period.

It's interesting because we don't have data for short-term neoadjuvant endocrine therapy, but it felt like that was the right thing to do, knowing that there was some uncertainty about when we would actually get these patients to the operating room. We knew that this would at least allow some window for us to be able to delay [surgery] safely, [while] still treating their cancer.

What are some of the steps that were taken as the lockdown started to lift?

During the lockdown, we saw fewer new patients. Fewer people were getting screened and fewer people were getting diagnosed with breast cancer during that time; that gave us a little bit of wiggle room. When we did reopen, our operating rooms were not already packed with patients who have been diagnosed during that time; that provided us with a little more flexibility to get the patients who had been delayed into [the clinic for their surgery].

During the months of June and July, things were very busy because we were trying to treat patients who were just diagnosed and also move all our patients who were on those lists that we made during lockdown into their surgical phase of treatment. It went fairly smoothly. We would talk to patients every week to determine when we might be able to get them in. Some of [these conversations were on] when reconstruction would be available; that was something we didn't start again until July 2020. Some patients were delayed longer depending on what kind of surgery they needed.

It took a lot of interpersonal communication with each individual patient to figure out what the plan was going to be for them. Our operating rooms didn't open up to full capacity right away; they kind of did a limited ramp up. This [decision was made] to protect staff and to figure out how much PPE we had; we still had concerns about those things. It took some time over the course of June 2020 and July 2020 to get everything ramped up to normal volumes. After that, things have been operating fairly normally.

What changes have been made with regard to managing patients around the time of surgery?

When we first opened up, there were no visitors of any kind; that was really hard for people. Patients had to get dropped off to have their surgery and then picked up; they were not to be able to have anyone with them during that time. That was a huge change for all of us.

Also, we now wear full PPE the whole time [that we are working]. I never take off my mask now. I always have on my goggles and I always have on my head covering. Not seeing people's faces or being able to shake their hand when you meet them [were] all things we had to get used to. That was a hard part of re-entry; it was a completely different way of practicing.

What changes were made in the operating room?

Our protocols around intubation and extubation evolved over time. When we first started up, we were very cautious, allowing only the anesthesiologist and 1 person to be at the head of the bed with full protective gear on. We would wait 15 minutes outside the room to let the circulation of the ventilation system happen before we would re-enter. Part of that had to do with the lack of availability of testing. It took some time to be able to get enough tests available that we could actually start testing all patients. Once we had more tests available, then we started testing all patients [who needed surgery]. Then we were able to feel more comfortable with adjusting some of those protocols around intubation and extubation.

In the very beginning, we were very cautious. We did a slow ramp up [until] we got back to full volume, which happened over time. We also had an increase in test capacity, which allowed us to start testing all patients. Then, things [started to feel] a little bit more normal. We also then felt safe having 1 visitor per person, which made a difference. However, a whole bunch of things changed. Nothing is truly normal about what we're doing. We get the surgeries done, but the way we do it, who's in the room, and who's not in the room—all of that is still evolving on a regular basis.

Matsen Spotlights Best Practices for Breast Cancer Surgery Amidst the COVID-19 Crisis

A breast surgeon discusses the best practices for breast cancer surgery during the COVID-19 pandemic.

Breast Cancer Surgery in a Pandemic: What's the Best Approach?

The FDA granted a regular approval to sacituzumab govitecan (Trodelvy) for the treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who had 2 or more previous systemic therapies, with at least 1 being for metastatic disease.

Recommended dosing for the drug is 10 mg/kg once a week on days 1 and 8 of 28-day treatment cycles or until progression or unacceptable toxicity.

The approval was based on findings from the multicenter, open-label, randomized ASCENT trial (NCT02574455), which included 529 patients with unresectable or locally advanced metastatic TNBC who experienced progression on 2 or more chemotherapies, one of which could have been in the neoadjuvant setting if progression occurred within 12 months.

Participants in ASCENT were randomized 1:1 to receive either intravenous sacituzumab govitecan or physician’s choice of single-agent chemotherapy.

The primary endpoint of the study was progression-free survival (PFS) in patients without brain metastases, per RECIST 1.1 criteria. Average PFS was 4.8 months in the sacituzumab govitecan arm, compared with 1.7 months in the chemotherapy arm.

Sacituzumab govitecan also bested chemotherapy when it came overall survival (OS), with median OS being 11.8 months in the treatment arm compared to 6.9 months in the control arm.

Common adverse events from sacituzumab govitecan, which occurred in more than 25% of patients, were nausea, neutropenia, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, rash, decreased appetite, and abdominal pain.

The FDA granted a regular approval to sacituzumab govitecan (Trodelvy) for previously treated patients with unresectable locally advanced or metastatic triple-negative breast cancer.

FDA Approves Sacituzumab Govitecan for Pretreated, Metastatic TNBC

Data from the pivotal phase 3 KATHERINE (NCT01772472) has led to the addition of ado-trastuzumab emtansine (T-DM1; Kadcyla) to the HER2-positive breast cancer treatment arsenal, but the toxicities associated with the approach must be appropriately managed so that patients can continue to receive it, according to Jane L. Meisel, MD.

The phase 3 KATHERINE trial examined ado-trastuzumab emtansine (T-DM1; Kadcyla) vs trastuzumab (Herceptin) and showed that the former resulted in a 50% reduction in the risk of invasive disease recurrence or death (HR, 0.50; 95% CI, 0.39-0.64; 

 <.0001). These data led to the May 2019 FDA approval of T-DM1 for use as an adjuvant treatment in select patients with HER2-positive early breast cancer.

Notably, 25.7% of the patients in the T-DM1 arm experienced a grade 3 or higher adverse effect (AE) vs 15.4% in the trastuzumab arm. Additionally, 18% of patients in the T-DM1 arm experienced AEs that lead to discontinuation of treatment.1

“It's tricky because these patients have been through a lot,” Meisel said. “It's a diagnosis of breast cancer, first of all, and it is a relatively toxic, intense, up-front therapy. It’s not the easiest thing, but for many patients, particularly those with high-risk disease, it really does make a difference. We try to do all we can to support patients through that.”

® during an Institutional Perspectives in Cancer webinar on breast cancer, Meisel, an associate professor for the Departments of Hematology and Medical Oncology, and Gynecology & Obstetrics at Winship Cancer Institute, Emory University School of Medicine, discussed the use adjuvant T-DM1 and the management of associated toxicities and the benefit of the combination pertuzumab (Perjeta)/trastuzumab in HER2-positive breast cancer.

®: What were the implications of the phase 3 KATHERINE and FeDeriCa trials (NCT03493854) now that more mature data have read out?

: KATHERINE was a fascinating study because it not only allowed us to take a very high-risk group and randomize them to a potential intervention, but it also showed that they really did much better when, instead of being given just 1 year of trastuzumab after not achieving a pathologic complete response [pCR], they were switched over to adjuvant T-DM1. That 3-year progression free survival [PFS] difference of 11% is really statistically significant, as well as clinically significant, and this has changed the way we treat our patients. Routinely, we are switching [patients] over to T-DM1 as was done in KATHERINE, and I believe this will start to change outcomes, as we see more and more of these patients do better.

FeDeriCa was a study that looked at pertuzumab and trastuzumab given subcutaneously as opposed to intravenously, with the primary end point being pertuzumab concentration, so more of a pharmacologic/pharmacokinetic end point as opposed to a clinical end point. The authors also looked at PCR rates with the subcutaneous administration and found that both the trough concentrations as well as the PCR rates were the same with subcutaneous versus IV administration.

[This is an] intervention that changes convenience for the patient, and in terms of safety, particularly during the pandemic, [it can prevent] time spent in the infusion center. This is a preparation which, technically, could be given in one's home as opposed to even in the clinic. Certainly, for patients who want to have the port removed or don't want to receive IV treatment for longer than they have to, this offers an opportunity to do just a little injection as opposed to an infusion. In terms of quality of life for patients, which really is a huge [factor] after they've been through so much, this represents a major step forward.

Were there any prohibitive toxicities observed in KATHERINE?

In the study, approximately 18% of patients discontinued T-DM1 because of toxicity. Generally, the populations that we see in studies are inherently a motivated, relatively well population of patients, while those we see in clinic may have more comorbidities or may not be as motivated as those who choose to join trials. As such, more [efforts are needed] to monitor these patients and to encourage them to stay on the T-DM1 because it is a little more challenging than the pertuzumab/trastuzumab. However, the benefit is there, so when patients seem as though they're going to benefit and they fit the criteria for the trial, we do try to get them to stay on [the drug].

I find it works best if I tell patients about the possibility [of toxicity] in the beginning. When I describe the neoadjuvant, anti-HER2–directed regimen, I talk about the fact that we'll use their surgery as both a part of their treatment, but also as an information-gathering piece. The result of the surgery, whether they get to PCR or not, will inform the next step. If they get to PCR, [they] would [then receive] trastuzumab, likely plus pertuzumab, or switch to T-DM1 if they don't. Once I get closer to that time point after the surgery, and if the patient is going to receive T-DM1, then we talk about what that will look like.

Often, I do see the patients each visit with T-DM1, at least in the beginning, just to see whether they're experiencing [effects] like nosebleeds, gastrointestinal distress, or worsening neuropathy. These are some of the most common [effects] that we see with the T-DM1 regimens, so we prefer to get on top of these effects and manage them right away. [Then] patients can either make the decision to discontinue and go back to pertuzumab/trastuzumab if they need to or can feel empowered that we have ways to manage the AEs and get through as much of that year of T-DM1 as possible.

Could you elaborate on some of the strategies used to manage those toxicities?

With neuropathy, one of the main strategies that we have is gabapentin, which can be helpful. Additionally, there's solid clinical trial data that support that icing the fingers and toes during chemotherapy treatment helps prevent neuropathy from getting worse; that can also be empowering: to know that there's something they can do, or can try, to help with that. In terms of the nosebleeds, which can happen with T-DM1, it's important to keep the nostrils moist. Vaseline or nasal sprays [can be used] sparingly if the nosebleeds are particularly bothersome. If a patient is having recurrent nosebleeds, we will refer them to an ear, nose, and throat [specialist].

In terms of liver function abnormalities, we do encourage patients to not drink heavily while they're on treatment and to abstain from Tylenol or other medications that might interfere with liver function tests.

Also, [we see] fatigue, [which] is multifactorial. We certainly see that [when patients are] on breast cancer therapies of all kinds.

Turning to FeDeriCa, now that the subcutaneous administration is approved, do you believe that patients will be more likely to pursue that option if they experience a milder toxicity?

They might, because options are everything. Some patients may be sticklers for the data, who may say they want to wait a little longer and see more before they make the switch. For other patients, the pharmacokinetics, and the fact that it's FDA approved, may be enough for them. They may want to make the switch if they feel like it's palatable.

Insurance coverage may be another issue. I'm not sure that every insurance company is going to cover it to the same degree as they cover intravenous administration. Finances may play a role, but I do believe this is going to be something that has legs, for sure.

von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. 

. 2019;380(7):617-628. doi:10.1056/NEJMoa1814017

Miesel on Managing Toxicities With T-DM1 in HER2+ Breast Cancer

Data from the pivotal phase 3 KATHERINE has led to the addition of ado-trastuzumab emtansine to the HER2-positive breast cancer treatment arsenal, but the toxicities associated with the approach must be appropriately managed so that patients can continue to receive it.

Breast Cancer