Changing trastuzumab dosing strategies for breast cancer treatment can reduce greenhouse gas emissions, according to research published in JCO Oncology Practice.

Using a case-control simulation, researchers found that shortening treatment duration and lengthening the time between doses reduced greenhouse gas emissions per person, leading to a reduction in deaths due to these emissions.

For the simulation, the researchers used data from 102 patients with HER2-positive breast cancer, including 63 who received trastuzumab in the neoadjuvant setting, 57 who received it in the adjuvant setting, and 30 who received it in the metastatic setting.

A streamlined life-cycle analysis was performed for 3 different trastuzumab dosing strategies:

• A 6-month adjuvant period with dosing once every 3 weeks;
• A 6-month adjuvant period with dosing once every 4 weeks;
• A 12-month adjuvant period with dosing once every 4 weeks.

These 3 strategies were compared to the standard dosing strategy — 12 months of adjuvant therapy with a dosing interval of once every 3 weeks.

The 6-month period with dosing every 3 weeks was estimated to reduce greenhouse gas emissions per person by 9.9% in the adjuvant setting, but there were no reductions in the neoadjuvant or metastatic settings.

The 6-month period with dosing every 4 weeks was estimated to reduce greenhouse gas emissions per person by 4.5% in the neoadjuvant setting, 18.7% in the adjuvant setting, and 14.6% in the metastatic setting.

The 12-month period with dosing every 4 weeks was estimated to reduce greenhouse gas emissions per person by 4.5% in the neoadjuvant setting, 10.4% in the adjuvant setting, and 14.6% in the metastatic setting.

The estimated number of excess disability-adjusted life-years lost because of greenhouse gas emissions associated with trastuzumab treatment was:

• 8.1 with the standard dosing strategy; 
• 7.5 with the 6-month period and dosing every 3 weeks;
• 7.1 with the 12-month period and dosing every 4 weeks;
• 6.6 with the 6-month period and dosing every 4 weeks.

The estimated number of excess deaths worldwide due to greenhouse gas emissions associated with trastuzumab treatment was:

• 4.6 with the standard dosing strategy;
• 4.3 with the 6-month period and dosing every 3 weeks;
• 4.0 with the 12-month period and dosing every 4 weeks;
• 3.7 with the 6-month period and dosing every 4 weeks.

The researchers noted that there are limitations to this study, including that 6 months of adjuvant trastuzumab has not been found to be as effective as treatment for 12 months.

“Alternative dosing strategies may materially reduce the population health impacts of cancer care by reducing environmental impact,” the researchers concluded. “Clinical trials of alternative dosing strategies are justified on the basis of environmental and population health impacts.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

HealthDay News — Between ages 69 and 70 years, there is a decline in adjuvant therapy recommendations for early breast cancer, according to a study published online January 31 in the International Journal of Radiation Oncology, Biology, Physics.

Wesley J. Talcott, MD, from Yale School of Medicine in New Haven, Connecticut, and colleagues identified 2 cohorts with strong indications for adjuvant treatment, regardless of age, who underwent lumpectomy for early-stage breast cancer between 2004 and 2017. Cohort 1 (160,990 participants) had higher-risk features and was appropriate for radiation. Cohort 2 (394,946 participants) had hormone receptor positivity with tumors greater than 5mm and was appropriate for endocrine therapy.

The researchers found that the radiation recommendation among cohort 1 declined sharply at age 70 years, from 90 to 92% for those aged 50 to 69 years to 81% for those aged 70 years. At age 70 vs 69 years only, year-over-year age difference was an independent predictor of adjuvant radiation recommendation (odds ratio, 0.47). A small decline in endocrine therapy recommendation was seen at age 70 years for cohort 2, with year-over-year age difference a predictor of endocrine therapy recommendation at age 70 vs 69 years only (odds ratio, 0.86).

“Our study indicates that physicians should be mindful of how we factor age into treatment decisions and adopt a more nuanced approach, extending beyond defining patients as simply ‘young’ or ‘elderly,'” Talcott said in a statement.

Abstract/Full Text

Yu Fujiwara, MD, from Mount Sinai Beth Israel in New York City, and colleagues conducted a systematic review and meta-analysis to examine how adding an immune checkpoint blockade to perioperative therapy affects treatment-related adverse events. Data were included from 28 randomized controlled trials with 16,976 cancer patients.

The researchers found no significant association for addition of an immune checkpoint blockade with increased treatment-related deaths, and this finding was consistent across immune checkpoint blockade subtypes. Across 9864 patients treated with an immune checkpoint blockade, 40 fatal toxicities were identified, with pneumonitis the most common (15.0%); among 7112 patients who were not treated with an immune checkpoint blockade, 13 fatal toxicities were identified. The incidence rates of grade 3 to 4 treatment-related adverse events, adverse events leading to treatment discontinuation, and treatment-related adverse events of any grade were increased with the addition of an immune checkpoint blockade (odds ratios, 2.73, 3.67, and 2.60, respectively). Increased incidence rates of treatment-related deaths and grade 3 to 4 adverse events were seen in association with an immune checkpoint blockade vs placebo design primarily used as adjuvant therapy (odds ratios, 4.02 and 5.31, respectively), while incidence was not increased with the addition of an immune checkpoint blockade in the neoadjuvant setting.

“Our analysis points to a need for further research into risk factors and identification of appropriate biomarkers to predict both efficacy and toxicity associated with cancer immunotherapy,” Fujiwara said in a statement.

Several authors disclosed ties to the biopharmaceutical industry.

Abstract/Full Text (subscription or payment may be required)

Editorial (subscription or payment may be required)

Artificial intelligence (AI) chatbots can sometimes provide accurate information about cancers, but these tools have limitations, according to a pair of studies published in JAMA Oncology.^1,2

In the first study, researchers assessed chatbots’ responses to the top Internet searches related to 5 cancers.¹ The chatbots provided information that was generally of high quality but not always actionable, and it was written at a college reading level.

In the second study, researchers found that a chatbot’s responses to queries about cancer treatments did not always align with recommendations in National Comprehensive Cancer Network (NCCN) guidelines.²

Most-Searched Queries About Cancers

Alexander Pan, of SUNY Downstate Health Sciences University in Brooklyn, New York, and colleagues evaluated chatbots’ responses to the top 5 search queries for skin, colorectal, prostate, lung, and breast cancers.¹ All queries contained the terms “cancer symptoms” and “what is [specific cancer].”

The researchers tested 4 chatbots, ChatGPT, Perplexity, Chatsonic, and Bing AI. The team used the DISCERN validation tool to assess the quality of information the chatbots provided and the Patient Education Materials Assessment Tool (PEMAT) to analyze the understandability and actionability of responses. On a scale of 1-5 (DISCERN) or 0%-100% (PEMAT), higher scores on the validation tools indicated higher-quality responses.

The quality of the cancer information provided by the chatbots was high, with a median DISCERN score of 5 (range, 2-5). However, the information was of moderate understandability. The median PEMAT score was 66.7% (range, 33.3%-90.1%), which the researchers deemed “college reading level.” Furthermore, the chatbots often failed to provide actionable responses, with a median PEMAT score of 20.0% (range, 0%-40.0%).

“These limitations suggest that AI chatbots should be used supplementarily and not as a primary source for medical information,” the researchers concluded.

ChatGPT and Cancer Treatment Recommendations

Shan Chen, of Mass General Brigham in Boston, and colleagues evaluated whether ChatGPT responded to queries about cancer treatments with recommendations that were in line with NCCN guidelines.²

Because ChatGPT’s knowledge cutoff was September 2021, the researchers measured responses against the 2021 NCCN guidelines. Responses were assessed by board-certified oncologists. The researchers used 104 queries for breast, prostate, and lung cancer. The chatbot provided at least 1 treatment recommendation for 102 of the queries (98%). All of these responses included at least 1 NCCN-concordant recommendation, but 35 (34.3%) also included at least 1 non-concordant recommendation. Additionally, 13 of 104 chatbot responses (12.5%) were “hallucinated”, that is, they were not part of any recommended treatment for the specified cancer.

“The chatbot did not purport to be a medical device and need not be held to such standards,” the researchers noted. “However, patients will likely use such technologies in their self-education, which may affect shared decision-making and the patient-clinician relationship. Developers should have some responsibility to distribute technologies that do not cause harm, and patients and clinicians need to be aware of these technologies’ limitations.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.

Alisertib monotherapy has shown activity in postmenopausal patients with endocrine-resistant, HER2-negative, metastatic breast cancer, according to research published in JAMA Oncology.

However, alisertib was not able to restore sensitivity to fulvestrant in this patient population. There was no difference in response or survival outcomes between patients who received alisertib monotherapy and those who received fulvestrant and alisertib in combination. 

This phase 2 trial (ClinicalTrials.gov Identifier: NCT02860000) included 91 patients with endocrine-resistant, HER2-negative, metastatic breast cancer who had received prior endocrine therapy and CDK4/6 inhibitor therapy in the metastatic setting.

The patients were randomly assigned to receive alisertib monotherapy (n=46) or alisertib plus fulvestrant (n=45). Prior chemotherapy for metastatic disease was more common in the combination arm (68.9%) than in the monotherapy arm (47.8%). Most patients had secondary endocrine resistance, 76.1% in the monotherapy arm and 82.2% in the combination arm.  

Patients received a median of 6 cycles of alisertib monotherapy (range, 1-34) and a median of 4 cycles of combination treatment (range, 1-44). Disease progression was the most common reason for treatment discontinuation in the monotherapy arm (82.6%) and the combination arm (68.9%). The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were similar between the treatment arms. “[W]hile alisertib did not restore fulvestrant sensitivity and increase ORRs, promising clinical activity was observed with alisertib monotherapy,” the researchers wrote.

The ORR was 19.6% with alisertib and 20.0% with the combination. The median duration of response was 15.1 months in the monotherapy arm and 8.5 months with the combination. The median PFS was 5.6 months in the monotherapy arm and 5.4 months in the combination arm. The median OS was 22.7 months and 19.8 months, respectively. 

There were 17 patients who crossed over from the monotherapy arm to the combination arm after disease progression. After crossover, 1 patient achieved a partial response, and the median PFS was 3.7 months.

The most common grade 3 or higher adverse events in the monotherapy arm were neutropenia (43.4%), leukopenia (17.4%), and anemia (19.6%). The most common grade 3 or higher adverse events in the combination arm were neutropenia (42.2%), leukopenia (31.1%), lymphopenia (15.6%), fatigue (11.1%), and anemia (8.9%).

The researchers concluded that alisertib “is among the first investigational targeted therapies demonstrating promising clinical activity and a tolerable safety profile” in patients with endocrine- and CDK4/6 inhibitor-resistant metastatic breast cancer.

Disclosures: This research was supported by Takeda Oncology. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Haddad TC, Suman VJ, D’Assoro AB, et al. Evaluation of alisertib alone or combined with fulvestrant in patients with endocrine-resistant advanced breast cancer: The phase 2 TBCRC041 randomized clinical trial. JAMA Oncol. Published online March 9, 2023. doi:10.1001/jamaoncol.2022.7949

The American Society of Clinical Oncology (ASCO) has released guidelines on how to treat patients amid current cancer drug shortages. The guidelines were published in JCO Oncology Practice.

Cancer drug shortages in the US have “reached unprecedented levels,” according to the guideline authors.

With this in mind, ASCO convened an advisory group of 44 experts to draft general principles on managing patient care during cancer drug shortages. The group also split into subgroups to address disease-specific guidance.

The advisory group’s general recommendations include:

• Do not order an agent with limited supply if an alternative treatment with comparable efficacy and safety is available.
• When clinically acceptable, increase the interval between cycles and/or reduce the total treatment dose of the agent in limited supply.
• Avoid using or minimize the use of a limited agent in recurrent cancers that are resistant to that agent.
• Minimize waste of limited agents by optimizing vial size, rounding doses, and using multiuse vials.
• If a particular agent is unavailable, use an evidence-based alternative regimen, obtaining a second opinion if necessary.
• Institutions should establish multidisciplinary committees to communicate internal policies on drug utilization.
• Providers should offer counseling referrals for patients who are feeling distress about drug shortages.
• Institutions should offer support services for clinicians who are feeling distress.

The guidelines also include disease-specific treatment recommendations related to drugs in short supply.

For example, in patients with early-stage HER2-positive breast cancer, combination treatment with docetaxel, carboplatin, trastuzumab, and pertuzumab is recommended as neoadjuvant and adjuvant therapy. The guidelines recommend that, if carboplatin is in short supply, these patients can receive the drug at an area under the curve of 5.

If carboplatin is unavailable, these patients may receive doxorubicin and cyclophosphamide plus paclitaxel, trastuzumab, and pertuzumab. Simply eliminating carboplatin and treating patients with docetaxel, trastuzumab, and pertuzumab is also an option, as “data from the metastatic setting offers evidence that carboplatin does not add a significant benefit,” the guideline authors wrote.

However, for some cancers, non-platinum regimens are considered inferior, and no suitable alternatives exist. In these cases, the advisory group recommends that patients to travel to an area where the appropriate treatment is available.

“While it is recognized that this strategy may cause additional financial toxicity, hardship, and distress, to optimize patient outcomes, it is encouraged if feasible,” the authors wrote.

For patients enrolled in clinical trials, the advisory group suggests that providers contact the lead investigator for guidance on maintaining compliance with study protocols. “Shortages will endure until the pharmaceutical supply chain is strengthened and investment in quality production of generic injectable drugs occurs,” the authors wrote.

Up-to-date information on cancer drug shortages is available at asco.org/drug-shortages.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Results from the AVIATOR trial showed that incorporating avelumab into treatment with vinorelbine and trastuzumab improved the response rate and progression-free survival (PFS).

This phase 2 study (ClinicalTrials.gov Identifier: NCT03414658) enrolled patients with advanced, HER2-positive breast cancer who were heavily pretreated but had not received prior immunotherapy or vinorelbine.

Patients were randomly assigned into 1 of 3 treatment arms: vinorelbine plus trastuzumab (n=18), vinorelbine plus trastuzumab and avelumab (n=45), and vinorelbine plus trastuzumab, avelumab, and utomilumab (n=34).

Clinical development of utomilumab was stopped in 2021, and that arm was closed to further enrollment. Results from the utomilumab arm were not presented at the symposium. 

The median PFS was 2.0 months with vinorelbine plus trastuzumab and 3.8 months with avelumab plus vinorelbine and trastuzumab (hazard ratio [HR], 0.53, 90% CI, 0.31-0.91; P =.025).

The overall response rate was 11.1% in the vinorelbine-trastuzumab arm (2 partial responses) and 20.0% in the avelumab arm (1 complete response and 8 partial responses).

The median duration of response was not evaluable in the vinorelbine-trastuzumab arm and was 15.8 months in the avelumab arm.

The rate of grade 3-4 adverse events (AEs) was 61.1% in the vinorelbine-trastuzumab arm and 62.2% in the avelumab arm. The most common grade 3-4 AEs were anemia (11.1% vs 2.2%), decreased neutrophil count (38.9% vs 55.6%), and decreased white blood cell count (5.6% vs 17.8%). Two grade 3 immune-related AEs occurred in the avelumab arm.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Jacqueline W. Miller, MD, from the CDC in Atlanta, and colleagues estimated the prevalence of mammography use within the previous 2 years among women aged 40 to 74 years using data from the 2022 Behavioral Risk Factor Surveillance System.

The researchers found that state-level mammography use varied from 64.0 to 85.5% among women aged 50 to 74 years. There was an association noted for having health insurance and a personal health care provider with having had a mammogram within the previous 2 years. Mammography prevalence was 83.2 and 65.7% for those with no adverse SDOH and HRSNs and for those with 3 or more adverse SDOH and HRSNs, respectively, among women aged 50 to 74 years. Strong associations with not having had a mammogram within the previous 2 years were seen for life dissatisfaction, feeling socially isolated, experiencing lost or reduced hours of employment, receiving food stamps, lacking reliable transportation, and reporting cost as a barrier for access to care.

“Health care facilities, providers, and public health programs could consider developing policies and effective practices to conduct risk assessments for adverse SDOH and HRSNs and address SDOH and HRSNs such as cost to access health care, social isolation, lack of reliable transportation, and food insecurity,” the authors write.

Abstract/Full Text

Avzivi is a vascular endothelial growth factor inhibitor indicated for the treatment of:

• Metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment.
• Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen.
• Unresectable, locally advanced, recurrent or metastatic nonsquamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first-line treatment.
• Recurrent glioblastoma in adults.
• Metastatic renal cell carcinoma in combination with interferon alfa.
• Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.
• Epithelial ovarian, fallopian tube, or primary peritoneal cancer, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens.

The approval was based on a comprehensive data package that included a pharmacokinetic study (ClinicalTrials.gov Identifier: NCT05865574) in healthy individuals, as well as a phase 3 comparative study (ClinicalTrials.gov Identifier: NCT03329911) in patients with advanced nonsquamous non-small cell lung cancer.

“The global phase 3 clinical trial has confirmed that Avzivi is highly similar to Avastin in terms of efficacy, safety and immunogenicity,” said professor Li Zhang, leading investigator for global phase 3 study of Avzivi. “The approval of Avzivi by the FDA will provide lung and colorectal cancer patients a new cost-effective treatment option.”

Undergoing a bilateral mastectomy does not decrease the risk of death in breast cancer patients who have a BRCA1 pathogenic variant, according to a study presented at the San Antonio Breast Cancer Symposium 2023.

The study showed that patients who underwent bilateral mastectomy were less likely to develop contralateral breast cancer than patients who underwent unilateral mastectomy or received breast-conserving treatment (BCT).

In addition, patients who developed contralateral breast cancer had a higher risk of death. However, there was no significant difference in the risk of death between patients who had a bilateral mastectomy and those who had a unilateral mastectomy or received BCT.

This study included 2482 patients from 11 countries who had stage I-III breast cancer and a BRCA1 pathogenic variant. The patients’ mean age was 43.1 (range, 18-70) years at breast cancer diagnosis, 46.0% underwent unilateral mastectomy, 34.3% underwent BCT, and 19.7% underwent bilateral mastectomy.

There were significant differences across the 3 surgical groups. Patients in the bilateral mastectomy group tended to be younger, diagnosed more recently, and had shorter follow-up than the other groups (P <.0001 for all).

Patients in the unilateral mastectomy group had larger tumors (P <.0001) and were more likely to have node-positive disease (P =.03). Patients who underwent bilateral mastectomy were more likely to undergo oophorectomy (P <.0001) and less likely to receive radiotherapy, chemotherapy, and tamoxifen (P £.0002 for all).

Over a mean follow-up of 8.9 years, 11.5% of patients were diagnosed with contralateral breast cancer, and 11.5% of patients died of breast cancer. The rate of contralateral breast cancer was higher in patients who underwent unilateral mastectomy (11.4%) and BCT (10.8%) than in patients who underwent bilateral mastectomy (0.8%; P <.0001).

In a multivariate analysis, patients with contralateral breast cancer had an increased risk of death (adjusted hazard ratio [aHR], 2.22; 95% CI, 1.49-3.32; P <.0001). This increased risk was seen in patients aged 40 years or younger (aHR, 2.71; 95% CI, 1.40-5.24; P =.003) and those older than 40 years of age (aHR, 1.99; 95% CI, 1.19-3.31; P =.008).

The mortality rate was higher in patients who underwent unilateral mastectomy (15.2%) than in those who underwent bilateral mastectomy (7.4%) or BCT (6.9%; P <.0001). The 15-year breast cancer-specific survival rates were 88.7% for bilateral mastectomy, 86.2% for BCT, and 78.7% for unilateral mastectomy.

In a multivariate analysis, however, there were no significant differences in the risk of death between patients who had BCT, those who underwent unilateral mastectomy (aHR, 1.22; 95% CI, 0.92-1.62; P =.17), and those who underwent bilateral mastectomy (aHR, 0.88; 95% CI, 0.58-1.13; P =.19).

“What we see from [these] data is that women with a BRCA1 pathogenic variant who elect for bilateral mastectomy [are] significantly less likely to develop a contralateral breast cancer,” said study presenter Kelly A. Metcalfe, RN, PhD, of the University of Toronto in Ontario, Canada.

“And women with a BRCA1 mutation who develop a contralateral breast cancer are twice as likely to die of breast cancer. However, bilateral mastectomy […] was not significantly associated with reduction in mortality compared to women with breast-conserving surgery. I think [these] data raise a lot of questions that we still need to answer.”

Disclosures: Dr Metcalfe declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a list of those disclosures.

Breakthroughs in targeted therapy and immunotherapy are partly responsible for the recent decline in cancer deaths seen in the United States, according to the AACR Cancer Progress Report 2023.¹

The overall rate of cancer death in the US fell by 33% between 1991 and 2020, which translates to 3.8 million lives saved, according to the report. Death rates have decreased for lung cancer, colorectal cancer, prostate cancer, female breast cancer, and melanoma.

“These gains have really reflected a whole variety of different advances, but mostly this has been about efforts in basic science,” AACR President Philip D. Greenberg, MD, of Fred Hutchinson Cancer Research Center in Seattle, said during a presentation about the AACR report.

Dr Greenberg noted that initiatives such as the Human Genome Project and The Cancer Genome Atlas have enabled the creation of targeted therapies, which are “increasingly precise and decreasingly toxic.”

Immunotherapy breakthroughs have also reduced the toxicity of treatments, leading to improved quality of life for patients. “Precision oncology, personalized medicine; it’s about creating drugs and using them to very selectively target the disease and not injure the person,” Dr Greenberg summarized.

The AACR report highlighted several targeted therapies with unique mechanisms of action that have been approved by the US Food and Drug Administration (FDA) since the early 2000s, including gefitinib in 2003, crizotinib in 2011, and sotorasib in 2021.

All of these therapies were approved to treat lung cancer, and these approvals coincided with declining lung cancer deaths. The decrease in lung cancer deaths per year grew from 0.9% between 1995 and 2005 to nearly 5% between 2014 and 2020.

The report also highlighted more recent FDA approvals. Between August 1, 2022, and July 31, 2023, the FDA approved 14 new cancer therapies and expanded the approved use of 12 therapies to encompass new cancers. The therapies include a range of cell-signaling inhibitors, antibody-drug conjugates, bispecific antibodies, and immune checkpoint inhibitors.

“A decade ago, there was 1 single immune checkpoint inhibitor,” Dr Greenberg pointed out. “Now . . . 11 checkpoint inhibitors have now been approved by the FDA up through 2023. And rather than using it to treat the single disease that it was approved for a decade ago, we now use it to treat 20 diseases.”

Two new imaging agents — pafolacianine and flotufolastat fluorine-18 —were also approved by the FDA between August 1, 2022, and July 31, 2023.

Ongoing Challenges

“Of course, despite all this progress, there’s a whole lot of work that needs to be done,” Dr Greenberg said. “There are still, even now, structural barriers for lots of people. There’s clearly disproportionate medical care being delivered to medically underserved populations. This includes, of course, racial and ethnic minorities, but it also includes the rural populations, which is not commonly appreciated, but rural populations participate very minimally in cancer trials.”

“Similarly, although precision medicine has really improved outcomes, we need ways of expanding that so that it includes more diseases,” Dr Greenberg added. “Pancreatic cancer, for example, and glioblastoma still have horrible 5-year relative survival rates, and so we need new advances.”

To address some of these challenges, the AACR has launched a new initiative known as the AACR Cancer Centers Alliance.²  The initiative aims to encourage collaboration among US cancer centers and “accelerate the pace of discovery by providing an ongoing mechanism for transferring new knowledge, sharing resources . . ., and driving innovation that impacts cancer science, cancer care delivery, and science and health policy.”²

Dr Greenberg suggested that the future of cancer research is bright. “I really enthusiastically look forward to what can happen,” he said. “I think there’s no reason not to be optimistic. . . . We’re in this time of unparalleled opportunities.”

Disclosures: Dr Greenberg has relationships with Affini-T, Rapt Therapeutics, Elpiscience, Fibrogen, Immunoscape, Metagenomi, Earli, Catalio, and Nextech. No disclosures were provided in relation to the AACR Cancer Progress Report 2023. Some authors of the Cancer Discovery article declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the article for a full list of disclosures.

HealthDay News — For women with multiple ipsilateral breast cancer, breast-conserving therapy (BCT) with adjuvant radiation results in a low 8-year local recurrence rate, according to a study published online March 28 in the Journal of Clinical Oncology.

Judy C. Boughey, MD, from the Mayo Clinic in Rochester, Minnesota, and colleagues examined oncologic outcomes in women aged 40 years and older with 2 to 3 foci of biopsy-proven cN0-1 breast cancer undergoing BCT. Participants underwent lumpectomy with negative margins, which was followed by whole-breast irradiation with a boost to all lumpectomy beds. A total of 204 eligible patients (median age, 61 years) underwent protocol-directed BCT.

The researchers found that 6 patients developed local recurrence at a median follow-up of 66.4 months, for an estimated 5-year cumulative incidence of local recurrence of 3.1%. No associations were seen for patient age, number of sites of preoperative biopsy-proven breast cancer, estrogen receptor status and human epidermal growth factor receptor 2 status, and pathologic T and N categories with the risk for local recurrence. In an exploratory analysis, the 5-year local recurrence rate was 22.6 and 1.7%, respectively, in patients without and with preoperative magnetic resonance imaging.

“This broadening of indications for BCT greatly benefits this growing population of patients as breast conservation is associated with better patient satisfaction and potentially improved survival,” the authors write.

Several authors disclosed financial ties to the pharmaceutical and medical technology industries; one author has a study-related patent pending.

Abstract/Full Text (subscription or payment may be required)

The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for capivasertib in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, following recurrence or progression on or after an endocrine-based regimen.

Capivasertib is an investigational, oral selective adenosine triphosphate (ATP)-competitive inhibitor of all 3 AKT isoforms (AKT 1/2/3). The NDA is supported by data from the phase 3 CAPItello-291 trial (ClinicalTrials.gov Identifier: NCT04305496). The study assessed the efficacy of capivasertib plus fulvestrant, an estrogen receptor antagonist, vs placebo plus fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following recurrence or progression on or after aromatase inhibitor therapy (N=708).

Study participants were randomly assigned to receive capivasertib plus fulvestrant (n=355) or placebo plus fulvestrant (n=353). The dual primary endpoints were progression free survival in the overall trial population and in the AKT pathway biomarker-altered population; alterations within the AKT pathway occur in up to 50% of patients with advanced HR-positive breast cancer.

Results showed in the overall population, the combination of capivasertib and fulvestrant reduced the risk of disease progression or death by 40% compared with placebo plus fulvestrant (hazard ratio [HR], 0.60 [95% CI, 0.51-0.71]; P <.001; median 7.2 vs 3.6 months). Among patients with AKT pathway-altered tumors, capivasertib plus fulvestrant reduced the risk of disease progression or death by 50% compared with placebo plus fulvestrant (hazard ratio [HR], 0.50 [95% CI, 0.38-0.65]; P <.001; median 7.3 vs 3.1 months).

At the time of the analysis, overall survival data (secondary endpoint) were immature; the trial continues to assess this endpoint.

“This Priority Review decision underscores the potential of capivasertib to extend the effectiveness of endocrine-based treatment approaches for patients with HR-positive breast cancer who experience tumor progression on, or resistance to these widely used therapies,” said Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca. “We look forward to working with the FDA to bring this potential first-in-class AKT inhibitor to patients as quickly as possible.”

A regulatory decision is expected in the fourth quarter of 2023. Capivasertib was previously granted Fast Track designation by the FDA in this setting for this patient population.

HealthDay News — Artificial intelligence (AI) chatbots generally produce accurate information for the top cancer-related web searches, according to a report published online August 24 in JAMA Oncology.

Alexander Pan, from State University of New York Downstate Health Sciences University in Brooklyn, and colleagues assessed the quality of information and presence of misinformation about cancers generated by 4 AI chatbots. The analysis included 100 text responses to the five most commonly searched queries (Google Trends) related to the five most common cancers (skin, lung, breast, colorectal, and prostate).

The researchers found that the quality of text responses generated by the 4 AI chatbots was good (median DISCERN score of 5), and no misinformation was identified. Understandability was rated as moderate using the Patient Education Materials Assessment Tool (median understandability score, 66.7%), while actionability was poor (median actionability score, 20.0%). Based on the Flesch-Kincaid Grade Level score, the responses were written at the college level.

“These limitations suggest that AI chatbots should be used supplementarily and not as a primary source for medical information,” the authors write.

Abstract/Full Text (subscription or payment may be required)

The combination yielded a clinical benefit rate of 97% and a median progression-free survival (PFS) of 21.2 months. The median overall survival (OS) was not reached at a median follow-up of 30.3 months.

This phase 1/2 trial (ClinicalTrials.gov Identifier: NCT03304080) enrolled patients with HR-positive, HER2-positive, previously untreated metastatic breast cancer.

There were 30 patients, 6 from the phase 1 portion and 24 from the phase 2 portion, who received the maximum tolerated dose (MTD) of palbociclib. Their median age was 57.6 years, 72.4% were postmenopausal, 43% had de novo disease, and 63.3% had visceral metastases.

The patients received the MTD of palbociclib (125mg on days 1 to 21 followed by 7 days off) along with standard doses of trastuzumab (8mg/kg loading dose followed by 6mg/kg every 21 days), pertuzumab (840mg/kg loading dose followed by 420mg/kg every 21 days), and anastrozole (1mg daily).

The median follow-up was 30.3 months. The objective response rate was 73%, and the clinical benefit rate was 97%. There were 4 complete responses, 18 partial responses, and 7 cases of stable disease.

The median time to response was 2.8 months, and the median duration of response was 37.8 months. The median PFS was 21.2 months. The PFS rate was 100% at 6 months, 71.2% at 12 months, 46.1% at 24 months, and 24.6% at 48 months.

The median OS was not reached. The OS rate was 100% at 6 months, 12 months, and 24 months. At 48 months, the OS rate was 88.9%. One patient had died at last follow-up.

Common adverse events (AEs) included neutropenia (87%), diarrhea (83%), leukopenia (77%), anemia (70%), fatigue (60%), nausea (53%), hyperglycemia (50%), and epistaxis (47%). Grade 3-4 AEs included neutropenia (46%), leukopenia (23%), anemia (17%), diarrhea (10%), hyperglycemia (10%), and fatigue (3%).

“Our trial found that the combination of anastrozole, palbociclib, trastuzumab, and pertuzumab in the frontline setting was well tolerated and effective, with a clinical benefit rate of 97%,” said study presenter Amy Tiersten, MD, of Mount Sinai in New York, New York. “This combination can provide a chemotherapy-free frontline regimen.”

Disclosures: This research was supported by Pfizer. Dr Tiersten disclosed relationships with AstraZeneca, Lilly/Loxo, Novartis, and Pfizer. No other disclosures were provided.

Chemotherapy-Induced Nausea and Vomiting Prophylaxis

The cisplatin shortage that has affected cancer centers and patients across the US is nearly resolved, according to a statement from the Biden Administration.¹

The White House reported last week that the cisplatin supply has been restored to almost 100% of pre-shortage levels.

According to the US Food and Drug Administration’s (FDA) drug shortage database, 3 companies had cisplatin available on allocation as of September 18.² Additional supplies of cisplatin are expected to be released this month and next month.

The shortage of cisplatin has occurred alongside prolonged shortages of several other cancer drugs, including methotrexate and carboplatin.³ In June, the National Comprehensive Cancer Network (NCCN) published survey results reporting that cisplatin was in short supply at 70% of included cancer centers, and carboplatin was in short supply at 93%.⁴

The FDA has worked to alleviate these shortages over the past several months.¹ In June, the FDA announced that it would work with Chinese drugmaker Qilu Pharmaceutical and Canadian pharmaceutical company Apotex to temporarily import cisplatin.⁵ According to the FDA, distribution of this product has been completed.²

The FDA also worked with various drug manufacturers to increase production of cisplatin, carboplatin, and methotrexate.¹ According to the FDA database, several companies have methotrexate and carboplatin available now, and additional supplies of both drugs are expected this month and next month.²

“The Administration will continue to work through the FDA, the Department of Health and Human Services, and other agencies to address and prevent drug shortages and mitigate impacts to people facing a cancer diagnosis,” the White House said in its statement.¹

Jolie Jean, MD, from Weill Cornell, and Yolanda Bryce, MD, from the Memorial Sloan Kettering Cancer Center, both in New York City, presented their technique for cryoablation of primary breast cancer (treated from January 2017 to March 2023). The analysis included 60 patients with breast cancer (48 had invasive ductal carcinoma) who were poor surgical candidates or refused surgery.

The researchers found that during a median follow-up of 16 months, there was a recurrence rate of 10% (6 patients). The risk for recurrence was higher among patients with poorly differentiated disease (risk ratio, 5.5). Invasive lobular carcinoma, estrogen receptor or progesterone receptor, and triple-negative status were not associated with risk. Furthermore, tumor size was similar between the recurrence and nonrecurrence groups (2.53 and 2.54cm, respectively).

“Surgery is still the best option for tumor removal, but there are thousands of women who, for various reasons, cannot have surgery,” Bryce said in a statement. “We are optimistic that this can give more women hope on their treatment journeys.”

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