Adstiladrin^® (nadofaragene firadenovec-vncg) is now fully available for the treatment of adults with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. 

Adstiladrin is a nonreplicating adenoviral vector-based gene therapy that delivers a copy of a gene encoding a human interferon-alfa 2b (IFNα2b) to the bladder urothelium. The treatment, which is administered by intravesical instillation once every 3 months, is expected to produce anti-tumor effects as a result of cell transduction and transient local expression of the IFNα2b protein.

The efficacy and safety of Adstiladrin was based on data from an open-label, multicenter, single-arm phase 3 trial (ClinicalTrials.gov Identifier: NCT02773849), which included 103 adults with BCG-unresponsive, high-risk, NMIBC with CIS with or without papillary tumors following transurethral resection. Results showed a complete response rate of 51% (95% CI, 41-61). Median duration of response was 9.7 months (range, 3 to 52+ months), and 46% of responders continued to remain free of high-grade recurrence at 12 months.

The most common adverse reactions reported were increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition, increased creatinine, hematuria, decreased phosphate, chills, pyrexia, and dysuria.

Adstiladrin is supplied in a carton containing 4 vials. All vials contain a nominal concentration of 3 x 10¹¹ viral particles per mL, and each vial contains an extractable volume of no less than 20mL. The treatment is administered by intravesical instillation and should be retained in the bladder for 1 hour before voiding.

To evaluate early utilization and outcomes with Adstiladrin in a real world setting, Ferring has initiated the non-interventional ABLE-41 study (ClinicalTrials.gov Identifier: NCT06026332).

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.

The Food and Drug Administration (FDA) has approved Anktiva^® (nogapendekin alfa inbakicept-pmln) with Bacillus Calmette-Guérin (BCG) for adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

Nogapendekin alfa inbakicept-pmln is an interleukin-15 receptor agonist. Binding of nogapendekin alfa inbakicept-pmln to its receptor results in proliferation and activation of natural killer, CD8+, and memory T cells. 

“This novel mechanism of action, which mimics the biology of the dendritic cell, begins the evolution of immunotherapy beyond T cells alone,” said Patrick Soon-Shiong, MD, Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. “The combination of the proliferation of key cancer-killing immune cells, together with the activation of T cells with memory, results in durable complete responses.”

The approval was based on data from the phase 2/3, open-label QUILT-3.032 study (ClinicalTrials.gov Identifier: NCT03022825), which included 77 patients with BCG-unresponsive, high-risk, NMIBC with CIS with or without Ta/T1 papillary disease following transurethral resection.

Study participants (median age, 73 years; 86% male; 90% White) received nogapendekin alfa inbakicept-pmln administered intravesically with BCG during the induction period followed by maintenance therapy for up to 37 months. The major efficacy outcomes were complete response (defined by negative results for cystoscopy and urine cytology) and duration of response.

Findings showed 62% (95% CI, 51-73) of patients achieved a complete response. The duration of response ranged from 0 to 47.0+ months; 58% (n=28) of patients with complete response had responses lasting at least 12 months and 40% (n=19) had responses lasting at least 24 months.

The most common adverse reactions reported with treatment were increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills and pyrexia.

Anktiva is supplied as a 400mcg/0.4mL solution in single-dose vials for intravesical instillation after dilution. According to the Company, the product is expected to be available by mid-May 2024.

The American Urological Association (AUA) and Society of Urologic Oncology (SUO) have released a new guideline on the management of nonmetastatic upper tract urothelial carcinoma (UTUC). The guideline, published in The Journal of Urology, provides evidence-based recommendations on diagnosis, risk stratification, and treatment of UTUC, a rare but often fatal disease. Below is a synopsis of the report’s major recommendations to surgeons.

Diagnosis and Evaluation

For patients with suspected UTUC, perform cystoscopy and cross-sectional imaging of the upper tract with contrast, according to the guideline report. In likely cases, perform diagnostic ureteroscopy, biopsy of lesions, and cytologic washing of the upper tract.

When ureteroscopy is not possible, attempt selective upper tract washing or barbotage for cytology. Use pyeloureterography in the absence of computed tomography or magnetic resonance urography.

In patients with high probability of Lynch-related cancers, perform universal histologic testing of UTUC with additional studies, such as immunohistochemical or microsatellite instability.

Risk Stratification

To facilitate clinical staging and risk assessment, the report recommends documenting the focality, location, appearance, and size of lesions based on endoscopy and recording features such as invasion, obstruction, and lymphadenopathy observed on imaging.

After standardized assessment, stratify patients as “low” or “high” risk for invasive pT2 or higher disease based on endoscopic, cytologic, pathologic, and radiographic findings. Further stratify patients into favorable and unfavorable risk groups.

Treatment

Tumor ablation, a nephron-sparing option, is recommended for patients with favorable low-risk UTUC. Tumor ablation also may be offered to patients with unfavorable low-risk UTUC and select patients with favorable high-risk UTUC who have low-volume tumors or cannot undergo radical nephroureterectomy (RNU), according to the report. After ablation and ruling out perforation, consider instilling adjuvant pelvicalyceal chemotherapy. When tumor ablation isn’t feasible or progression has occurred, perform RNU or segmental resection of the ureter.

Surgery: Perform RNU or segmental ureterectomy in suitable high-risk UTUC cases. When performing RNU or distal ureterectomy, excise the entire distal ureter including the intramural ureteral tunnel and ureteral orifice, and seal the urinary tract. Also perform lymph node dissection. Follow with a single dose of perioperative intravesical chemotherapy. Clinicians also may consider lymph node dissection in low-risk cases.

Chemotherapy and Immunotherapy

Clinicians should offer cisplatin-based neoadjuvant chemotherapy to surgery patients with high-risk UTUC. They should offer platinum-based adjuvant chemotherapy to patients with advanced pathologic stage UTUC after RNU or ureterectomy if they have not received neoadjuvant platinum-based therapy.

Adjuvant nivolumab therapy may be given to patients who received neoadjuvant platinum-based chemotherapy and have ypT2-T4 or ypN+ disease or patients with pT3, pT4a, or pN+ disease who are ineligible for perioperative cisplatin.

The full guideline also provides recommendations for UTUC surveillance.

Applying the Guideline

At the American Urological Association’s 2023 Annual Scientific Meeting, Surena F. Matin, MD, of MD Anderson Cancer Center in Houston, Texas, asked a panel of urologists focused on UTUC treatment for advice on applying the new AUA/SUO guideline in clinical practice. The panel included Jay D. Raman, MD, of Penn State Health Milton S. Hershey Medical Center in Pennsylvania, Sima P. Porten, MD, MPH, of University of California, San Francisco, and Tomonori Habuchi, MD, of Akita University in Japan. The panel debated management of real-world patients with low-grade UTUC, and high-grade, high-risk UTUC who had good kidney function.

Dr Matin summarized the take-home messages from the debate in an AUA news article:

Managing low-grade UTUC

• Consider mitomycin hydrogel for low-grade recurrent UTUC
• Use intravesical chemotherapy with nephroureterectomy
• Consider intravesical chemotherapy after ureteroscopic biopsy, based on anecdotal evidence

Managing high-risk UTUC

• Risk stratify upper tract tumors
• Estimate post-nephroureterectomy kidney function to help patients decide between initial surgery or neoadjuvant chemotherapy
• Consider lymphadenectomy

The new AUA/SUO guideline follows the release of the European Association of Urology’s 2020 update to its UTUC guideline.

The efficacy of erdafitinib was supported by data from cohort 1 of the phase 3 THOR study (ClinicalTrials.gov Identifier: NCT03390504), which compared erdafitinib to standard of care chemotherapy (investigator’s choice of docetaxel or vinflunine). Cohort 1 included 266 adults with advanced urothelial cancer harboring selected FGFR3 alterations. 

All patients had disease progression after 1 or 2 prior treatments, at least 1 of which included a programmed death receptor 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. The major efficacy endpoints were overall survival (OS), progression free survival (PFS) and objective response rate (ORR).

Findings showed treatment with erdafitinib reduced the risk of death by 36% compared with chemotherapy (hazard ratio [HR], 0.64 [95% CI, 0.47-0.88]; P =.005). Median OS was 12.1 months in the erdafitinib arm vs 7.8 months in the chemotherapy arm. Median PFS was 5.6 months in the erdafitinib arm vs 2.7 months in the chemotherapy arm (HR, 0.58 [95% CI, 0.44-0.78; P =.0002). ORR was 35.3% (5.1% with complete response and 30.1% with partial response) with erdafitinib vs 8.5% (0.8% with complete response and 7.7% with partial response) with chemotherapy.

Patients should be selected for treatment based on the presence of susceptible FGFR3 generic alterations in tumor specimens as detected by an FDA-approved companion diagnostic. Balversa is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy.

Balversa is supplied as a tablet in 3mg, 4mg, and 5mg dosage strengths. 

The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental News Drug Application (sNDA) for belzutifan for the treatment of adults with advanced renal cell carcinoma (RCC) following immune checkpoint and anti-angiogenic therapies.

Belzutifan is a hypoxia-inducible factor inhibitor currently marketed under the brand name Welireg for the treatment of adult patients with von Hippel-Lindau disease who require therapy for associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery. Merck is seeking approval of belzutifan in patients with advanced RCC based on data from the LITESPARK-005 trial (ClinicalTrials.gov Identifier: NCT04195750).

The open-label phase 3 study compared belzutifan to everolimus in patients with advanced RCC who had progressed after treatment with a programmed cell death 1 ligand 1 checkpoint inhibitor and a vascular endothelial growth factor – tyrosine kinase inhibitor (in sequence or in combination). Study participants (n=746) were randomly assigned to receive belzutifan 120mg orally once daily or everolimus 10mg orally once daily. The coprimary endpoints were progression free survival (PFS) and overall survival (OS).

Findings showed a statistically significant and clinically meaningful improvement in PFS with belzutifan compared with everolimus. A statistically significant improvement in objective response rate (secondary endpoint) was also noted. While an improvement in OS was observed at the interim analysis, it was not considered statistically significant, and is expected to be tested at a subsequent analysis, according to the Company. 

“Patients with advanced RCC whose cancer progresses following immune checkpoint and anti-angiogenic therapies face a poorer prognosis, and for those patients, there is a crucial unmet need for new options with an alternative mechanism of action,” said Dr Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. “The FDA’s Priority Review designation of this application reinforces the urgency to provide new options to previously treated patients with advanced RCC, and we are committed to working closely with the FDA to bring Welireg to these patients as quickly as possible.”

A Prescription Drug User Fee Act target date of January 17, 2024 has been set for the application.

HealthDay News — For patients with advanced renal cell carcinoma, progression-free survival and overall survival are improved with lenvatinib plus pembrolizumab vs sunitinib, according to a study published in the March issue of The Lancet Oncology.

Toni K. Choueiri, MD, from the Dana-Farber Cancer Institute in Boston, and colleagues conducted a protocol-prespecified updated overall survival analysis of the phase 3 CLEAR trial. Patients with clear-cell advanced renal cell carcinoma who had not received any systemic anticancer therapy were eligible and randomly assigned to receive lenvatinib plus pembrolizumab, lenvatinib plus everolimus, or sunitinib (355, 357, and 357, respectively). This updated analysis did not report on patients in the lenvatinib plus everolimus group.

The median follow-up for progression-free survival was 27.8 and 19.4 months in the lenvatinib plus pembrolizumab group and the sunitinib group, respectively. The researchers found that median progression-free survival was 23.3 and 9.2 months in the lenvatinib plus pembrolizumab group and sunitinib group, respectively (stratified hazard ratio, 0.42). For overall survival, median follow-up was 33.7 and 33.4 months in the lenvatinib plus pembrolizumab group and sunitinib group, respectively; overall survival was improved with lenvatinib plus pembrolizumab vs sunitinib (hazard ratio, 0.72).

“This extended follow-up analysis shows the durable and clinically meaningful efficacy benefit with lenvatinib plus pembrolizumab over sunitinib,” the authors write. “Previously observed benefits in overall survival, progression-free survival, and objective response rate were maintained.”

Several authors disclosed financial ties to biopharmaceutical companies, including Eisai and Merck, which manufacture lenvatinib (Eisai) and pembrolizumab (Merck) and funded thev study.

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

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.”

HealthDay News — The bacillus Calmette-Guerin (BCG) vaccine is associated with a significantly lower rate and risk for Alzheimer disease and related dementias (ADRD) among patients with bladder cancer, according to a study published online May 19 in JAMA Network Open.

Marc S. Weinberg, MD, PhD, from Massachusetts General Hospital in Boston, and colleagues evaluated whether the BCG vaccine (3388 patients) has a protective association with the risk for ADRD. The analysis included 6467 patients (aged 50 years and older) initially diagnosed with non-muscle-invasive bladder cancer between May 28, 1987, and May 6, 2021.

The researchers found that treatment with the BCG vaccine was associated with a lower rate of ADRD (hazard ratio [HR], 0.80), with an even lower rate of ADRD in patients aged 70 years or older at the time of BCG vaccine treatment (HR, 0.74). The BCG vaccine was associated with a lower risk for ADRD (5-year risk difference, −0.011) and a decreased risk for death in patients without an earlier diagnosis of ADRD (5-year risk difference, −0.056) in a competing risks analysis.

“In this study, BCG vaccine was associated with a significantly lower rate and risk of ADRD in a cohort of patients with bladder cancer when accounting for death as a competing event. However, the risk differences varied with time,” the authors write. “Clinical trials are required to study its efficacy beyond treatment in patients with bladder cancer.”

Several authors disclosed ties to the biotechnology and pharmaceutical industries.

Abstract/Full Text

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.

Cancer patients were more likely to die from the BA.1 and BA.2 omicron variants of SARS-CoV-2 than from wild-type SARS-CoV-2, according to research published in JAMA Oncology.^1,2

The study showed that, among US cancer patients, COVID-19 deaths were more likely during the initial omicron wave when the BA.1 and BA.2 variants were in circulation (December 2021 to February 2022) than when wild-type SARS-CoV-2 was circulating (December 2020 to February 2021).

According to data from the US Centers for Disease Control and Prevention, there were 54,692 COVID-19 deaths among patients with cancer and 1,008,510 COVID-19 deaths in the general population from March 1, 2020, through May 31, 2022.

This study included 34,350 patients with cancer and 628,156 individuals from the general population who died from COVID-19 when wild-type SARS-CoV-2 was in circulation (December 2020-February 2021), the delta variant was in circulation (July 2021-November 2021), or the BA.1 and BA.2 omicron variants were in circulation (December 2021-February 2022).

The highest number of COVID-19-related deaths among patients with cancer occurred during the 2021-2022 omicron wave. At the peak of this wave, in January 2022, there were 18% more deaths than during the peak of the wild-type period, which occurred during January 2021.

This trend was maintained when patients were stratified by age group. The number of deaths per month among patients with cancer younger than 50 years of age was 64% higher during the 2021 to 2022 omicron wave than during the wild-type wave. The number was 62% higher among patients aged 50 to 59 years, 31% higher for those aged 60 to 69 years, and 16% higher for those aged 70 to 79 years.

When the researchers looked at individual cancer types, they found that COVID-19 deaths were more likely during the 2021-2022 omicron wave for most cancer types. The exceptions were brain cancer (mortality ratio [MR], 0.77; 95% CI, 0.65-0.90), thyroid cancer (MR, 0.76; 95% CI, 0.54-0.99), and bladder cancer (MR, 0.58; 95% CI, 0.52-0.65).

Patients with lymphoma had the greatest increase in deaths from the wild-type wave to the 2021 to 2022 omicron wave, at 38% (mortality ratio [MR], 1.38; 95% CI, 1.31-1.45).

In the general population, the highest number of COVID-19 deaths per month occurred when wild-type SARS-CoV-2 was prevalent. At the peak of the initial omicron wave in January 2022, there were 21% fewer deaths in the general US population than at the peak of the wild-type period in January 2021 (MR, 0.69; 95% CI, 0.69-0.70).

“[W]hile the general US population experienced a large reduction in COVID-19 mortality during the winter Omicron period, patients with cancer experienced the highest COVID-19 mortality during the winter Omicron period, likely due to increased SARS-CoV-2 exposure during this period combined with the reduced effectiveness of COVID-19 vaccines and increased risk of COVID-19 mortality in this population,” the researchers wrote. “With future COVID-19 waves imminent, strategies to protect those at highest risk should remain a high priority, even during future pandemic waves with less virulent SARS-CoV-2 variants.”

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

References

1. Potter AL, Vaddaraju V, Venkateswaran S, et al. Deaths due to COVID-19 in patients with cancer during different waves of the pandemic in the US. JAMA Oncol. Published online August 31, 2023. doi: 10.1001/jamaoncol.2023.3066

2. SARS-CoV-2 sequences by variant, United States, Jan 3, 2022. Our World in Data. Updated August 22, 2023. Accessed September 1, 2023.

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