HealthDay News — For patients with high-risk hepatocellular carcinoma (HCC), adjuvant therapy of atezolizumab with bevacizumab (atezo + bev) prolongs recurrence-free survival, according to a study presented at the annual meeting of the American Association for Cancer Research, held from April 14 to 19 in Orlando, Florida.

Pierce Chow, MBBS, PhD, from the National Cancer Center in Singapore, and colleagues examined the efficacy of adjuvant atezo + bev for delaying or preventing recurrence in patients with high-risk HCC following resection or ablation, with high risk based on tumor burden, vascular invasion, and tumor differentiation. Patients were randomly assigned to receive atezo + bev for a period of one year or 17 cycles or to undergo active surveillance (arms A and B, respectively); patients in arm B were eligible for crossover to atezo + bev following confirmed recurrence. The intention-to-treat population included 334 patients in each arm.

The researchers found that the primary end point of independent review facility recurrence-free survival was met with a hazard ratio of 0.72 at interim analysis with a median follow-up of 17.4 months; across clinical subgroups, the results were generally consistent. Similar investigator-assessed recurrence-free survival was seen (hazard ratio, 0.70). The safety of atezo + bev was consistent with the well-established safety profiles of each therapeutic agent.

“Due to the lack of proven adjuvant therapy strategies for HCC, patients who are treated with surgical resection or thermal ablation with curative intent tend to have significantly higher recurrence rates and shorter overall survival than patients with other types of cancer; for example, colorectal and breast cancer treated with similar curative intent,” Chow said in a statement. “The positive results of IMBrave050 address this huge and urgent unmet clinical need in HCC.”

Chow disclosed financial ties to pharmaceutical companies, including Genentech, the manufacturer of atezolizumab and bevacizumab. Parent company F. Hoffmann-La Roche funded the study.

Press Release

More Information

Adagrasib is a highly selective, potent oral small molecule inhibitor of KRAS^G12C designed to sustain target inhibition by irreversibly locking the mutant protein in its inactive state. The application is supported by data from the multicohort phase 2 KRYSTAL-1 study (ClinicalTrials.gov Identifier: NCT03785249), which evaluated adagrasib in heavily pretreated patients with KRAS^G12C-mutated advanced CRC.

Study participants received either adagrasib 600mg orally twice daily as monotherapy (n=44) or in combination with cetuximab administered intravenously once or twice weekly (n=32); median follow-up was 20.1 months and 17.5 months, respectively. The primary endpoint was the objective response rate (ORR). 

Among 28 evaluable patients in the adagrasib plus cetuximab arm, the ORR was 46% (95% CI, 28-66). Median duration of response (DOR) was 7.6 months (95% CI, 5.7-not estimable) and median progression-free survival (PFS) was 6.9 months (95% CI, 5.4-8.1).

Among 43 evaluable patients in the adagrasib monotherapy arm, the ORR was 19% (95% CI, 8-33). Median DOR was 4.3 months (95% CI, 2.3-8.3) and median PFS was 5.6 months (95% CI, 4.1-8.3). 

The safety profile of adagrasib plus cetuximab was well tolerated. The incidence of Grade 3 or 4 treatment-related adverse events was 34% in the monotherapy arm and 16% in the combination arm. There were no Grade 5 adverse events observed. 

A Prescription Drug User Fee Act target date of June 21, 2024 has been set for this application.

“Pretreated KRAS^G12C-mutated CRC is associated with poor outcomes and the current standard of care offers limited clinical benefit for patients,” said Anne Kerber, senior vice president, head of late clinical development, Hematology, Oncology, Cell Therapy (HOCT) at Bristol Myers Squibb. “It [sNDA acceptance] reinforces our commitment to developing potentially transformative targeted cancer therapies for patients for whom few treatment options exist.”

Adagrasib is currently marketed under the trade name Krazati^® and is approved for the treatment of adults with KRAS^G12C-mutated locally advanced or metastatic NSCLC, who have received at least 1 prior systemic therapy.

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.

First-Line Therapy

For patients with Child-Pugh class A advanced HCC who have an ECOG performance status score of 0 or 1, the guidelines recommend atezolizumab plus bevacizumab or durvalumab plus tremelimumab as first-line treatment (a strong recommendation based on moderate- to high-quality evidence).

Patients with contraindications to atezolizumab plus bevacizumab or durvalumab plus tremelimumab can receive sorafenib, lenvatinib, or durvalumab as alternatives (a strong recommendation based on moderate-quality evidence).

Second-Line Therapy

For patients with Child-Pugh class A advanced HCC who have good performance status, recommendations for second-line treatment vary based on the first-line treatment a patient received.

Patients who received first-line atezolizumab plus bevacizumab can receive any of the following second-line treatments:

• A tyrosine kinase inhibitor (TKI) — such as sorafenib, lenvatinib, or cabozantinib — or ramucirumab (a weak recommendation based on low-quality evidence)
• Nivolumab plus ipilimumab (supported by data from case series)
• Durvalumab plus tremelimumab. (There are no data to support this recommendation.)

If durvalumab plus tremelimumab is given in the first line, second-line therapy with a TKI is recommended (a weak recommendation based on low-quality evidence). Atezolizumab plus bevacizumab may also be considered, but there are no data to support this recommendation.

If a patient received sorafenib or lenvatinib in the first line, second-line therapy may consist of any of the following (a weak recommendation based on low-quality evidence):

• Another TKI (cabozantinib or regorafenib)
• Ramucirumab
• Nivolumab plus ipilimumab
• Durvalumab
• Atezolizumab plus bevacizumab (for patients who did not have access to this combination in the first line)
• Durvalumab plus tremelimumab (for patients who did not have access to this combination in the first line).

Pembrolizumab and nivolumab may also be options for patients who previously received sorafenib or lenvatinib.

Third-Line Therapy and Child-Pugh Class B HCC

For third-line therapy, patients with Child-Pugh class A disease and good performance status can receive any of the aforementioned agents, as long as they do not have an identical mechanism of action to prior therapies (weak recommendation based on low-quality evidence).

For patients with Child-Pugh class B disease and good performance status, health care providers should consider the patients’ underlying liver function, bleeding risk, presence of portal hypertension, extent of extrahepatic spread, tumor burden, and major vascular invasion. There are limited data to suggest that regimens typically used for Child-Pugh A disease can be beneficial in untreated patients with Child-Pugh B cirrhosis (weak recommendation based on low-quality evidence).

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

Ottavia De Simoni, MD, from Veneto Institute of Oncology IOV‐IRCCS in Padova, Italy, and colleagues conducted a retrospective analysis of 238 patients with a diagnosis of CRC operated on from 2015 to 2019 (METACCRE cohort) to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and the healthy mucosa surrounding cancer. mRNA expression of immune surveillance‐related genes (PD‐L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin was extracted; the experiment was repeated in cell lines. In a subgroup of patients, the mucosal immune microenvironment was analyzed with immunohistochemistry and flow cytometry.

Overall, 12% of the patients in the METACCRE cohort were aspirin users. The researchers found that aspirin users had nodal metastasis significantly less frequently and higher tumor-infiltrating lymphocyte infiltration. CD80 mRNA expression was increased following aspirin treatment in the CRC primary cells and selected cell lines. The ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users in the healthy mucosa surrounding rectal cancer.

“Our data suggested that aspirin use may be associated with a lower grading and nodal metastasis rate and a higher tumor-infiltrating lymphocytes infiltration in patients with CRC,” the authors write. “These results are more evident in the right colon where, realistically, the bioavailability of aspirin is higher.”

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.”

CTX-009 is a bispecific antibody that simultaneously blocks Delta-like ligand 4 and vascular endothelial growth factor A signaling pathways. The designation is supported by data from an open-label, single-arm phase 2 study (ClinicalTrials.gov Identifier: NCT04492033), which evaluated the safety, tolerability, and pharmacokinetics of CTX-009 in combination with paclitaxel in patients with unresectable advanced, metastatic or recurrent biliary tract cancer (N=24).

Findings showed an overall response rate (ORR) of 37.5% (95% CI, 18.8-59.4). Median duration of response and progression free survival were 9.4 months for both endpoints. Median overall survival was 12.5 months.

CTX-009 is currently being evaluated in combination with paclitaxel in the phase 2/3 COMPANION-002 study (ClinicalTrials.gov Identifier: NCT05506943) in adults with unresectable advanced, metastatic or recurrent biliary tract cancers who have received 1 prior systemic chemotherapy regimen. Topline data are expected by the end of 2024. 

“We are delighted that CTX-009 has received FDA Fast Track Designation highlighting the large unmet need in patients with advanced BTC where current therapies have low, single digit response rates, and limited effect on patient survival,” said Thomas Schuetz, MD, PhD, Co-founder, President of R&D, and Vice Chairman of the Compass board.

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.

Noting that the cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using Amphiphile (Amph)-modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909), Shubham Pant, MD, MBBS, from the University of Texas MD Anderson Cancer Center in Houston, and colleagues treated 25 patients (20 with pancreatic cancer; 5 with colorectal cancer) positive for minimal residual mKRAS disease after locoregional treatment in a phase 1 study involving fixed-dose Amph-Peptides-2P and ascending dose Amph-CpG-7909.

The researchers found no dose-limiting toxicities; the recommended phase 2 dose was 10mg Amph-CpG-7909. Overall, 21, 21, and 6 patients (84, 84, and 24%) had direct ex vivo mKRAS-specific T-cell responses, tumor biomarker responses, and biomarker clearance, respectively. Median relapse-free survival was 16.33 months. There was a correlation seen for efficacy with T-cell response; the median tumor biomarker reduction was −76.0 vs −10.2%. Median relapse-free survival was not reached compared with 4.01 months (hazard ratio, 0.14).

“Overall, this study provides important proof of concept for the safety and immunogenicity of lymph node-targeting Amphiphile vaccines and yielded promising signals of clinical activity that correlate with the magnitude of ELI-002 2P-induced T-cell response,” the authors write.

Several authors disclosed ties to biopharmaceutical companies, including Elicio Therapeutics, which is developing ELI-002 2P and funded the study.

Abstract/Full Text

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)

Chemotherapy-Induced Nausea and Vomiting Prophylaxis

The findings are based on analysis of data from Explorys Inc, a validated, multicenter and research platform database of more than 360 hospitals from 26 different US health care systems from 1999 to September 2022.

Eligible participants were aged over 18 years. Those with a history of familial adenomatous polyposis, a family history of CRC, and inflammatory bowel disease were excluded.

Multivariate regression analysis was used to calculate the risk for CRC and account for potential cofounders, including male sex, smoking history, alcoholism, obesity, type 2 diabetes, and those diagnosed with CTG. A 2-sided P value less than .05 was considered statistically significant.

A total of 70,177,200 individuals were included in the final analysis; 234,840 had CRC and 69,942,360 had no CRC. Type 2 diabetes (28.57% vs 7.90%), smokers (10.98% vs 5.33%), obesity (18.71% vs 7.59%), alcoholism (3.13% vs 1.53%), and patients who have had a diagnosis of CTG (0.08% vs 0.01%) were more common in the CRC group compared with those without CRC, respectively.

According to multivariate regression analysis, the risk for CRC was calculated for the male sex (odds ratio [OR], 1.02; 95% CI, 1.01-1.03), smokers (OR, 1.54; 95% CI, 1.52-1.56), alcoholism (OR, 1.40; 95% CI, 1.37-1.43), obesity (OR, 1.52; 95% CI, 1.50-1.54), type 2 diabetes (OR, 3.53; 95% CI, 3.50-3.57), and a diagnosis of CTG (OR, 1.40; 95% CI, 2.48-3.23).

“Uric acid is likely 1 of the culprits of this association, as it leads to increased production of reactive oxygen species and promotes tumorigenesis,” the researchers wrote. “Further research is required to assess the prevalence of colon cancer in patients with gout and serum uric acid that is <7 mg/dL. This will promote additional discussion about tighter control of serum uric acid levels in this population in order to decrease the overall risk of colon cancer.”

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

Although more people have access to CRC screening through the Veterans Health Administration (VA) than the rest of the United States general population, CRC remains a leading cause of cancer in veterans. For the study, researchers examined predictors of CRC diagnosis and whether the conventional measure could provide an accurate CRC screening status among individuals aged younger or older than 50 to 75 years.

Researchers conducted a case-control study using data from the VA clinical database to examine the relationship between screening status and CRC diagnosis. Among the study participants (N=3,714), 55% where White, 23.9% did not report race or ethnicity, 15.8% were Black, 4.5% were Hispanic or Latino, and 0.8% were Asian. Patients also had diabetes (26.7%) and obesity (32.4%).

Individuals with CRC were matched to control individuals according to age, sex, and facility. Researchers also grouped patients into 5 categories regarding screening status:

1. average-risk, aged 50 to 75 years, and up-to-date.
2. average-risk, aged 50 to 75 years, and not up-to-date.
3. average-risk, aged younger or older than 50 to 75 years, and up-to-date.
4. average-risk, aged younger or older than 50 to 75 years, and not up-to-date.
5. high-risk factors, such as inflammatory bowel disease, hereditary cancer syndromes, or family history of CRC.

The study used multivariable conditional logistic regression — adjusted for race and ethnicity, smoking history, obesity, diabetes, and alcohol consumption — to analyze the association between CRC and screening status. Patients in category 5 vs category 1 had an increased risk for CRC (odds ratio [OR], 5.58; 95% CI, 4.25-7.32). Asian vs White patients had a lower risk for CRC (OR, 0.55; 95% CI, 0.34-0.90), and Black patients had a higher risk (OR, 1.53; 95% CI 1.32-1.77). Diabetes (OR, 2.01; 95% CI, 1.78-2.26), obesity (OR, 1.18; 95% CI, 1.07-1.31), and heavy alcohol consumption (OR, 3.35; 95% CI, 2.85-3.94) were all associated with developing CRC.

Individuals with a history of smoking had a lower risk for CRC compared with never smokers (OR, 0.05; 95% CI, 0.04-0.06).

“The conventional measure of CRC screening, which focuses on average-risk individuals aged 50-75, does not reflect screening status in an important minority of patients with CRC,” the study authors wrote.