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

Coverage determination for oncology drugs can be delayed for months after regulatory approval, according to research published in JAMA Oncology.

Researchers found that coverage determination by pharmacy and therapeutics committees (PTCs) is “frequently delayed for months” after a cancer drug is approved by the US Food and Drug Administration (FDA). However, lag times vary, and the determination delay has improved over time, “suggesting that PTC determinations are becoming more efficient,” the researchers wrote.

For this study, the researchers evaluated the time from FDA approval to PTC determination between 2010 and 2019 for 127 payers. There were a total of 89 oncology drugs with 974 PTC determination dates.

The median coverage lag was 4.2 months, and the median lag range was 32.2 months. The median lag between oncology drug approval and PTC determination was 10.9 months in 2010, and this decreased to 3.4 months in 2018. The median lag range decreased from 39.8 months in 2010 to 14.4 months in 2018.

A more recent year of FDA approval was significantly associated with lower odds of a long lag between approval and determination (odds ratio [OR], 0.20; 95% CI, 0.07-0.59) and of a large lag range (OR, 0.54; 95% CI, 0.34-0.85).

There was no association between determination lag and drug class, orphan drug status, or FDA expedited review pathways, including fast track designation, priority review, and accelerated approval.

“These results indicate that PTC determinations are frequently delayed for months after initial FDA approval and that lag periods are highly variable among payers,” the researchers concluded. “Coupled with drug coverage being frequently subject to formulary exclusions and restrictions across many coverage plans, our results indicate that the existing payer system for oncology care may severely hamper patient access to effective drugs.”

Ranitidine does not pose an increased risk of cancer when compared to other histamine-2 receptor antagonists (H₂RAs), according to a study published in JAMA Network Open.

For this study, researchers analyzed data from health claims and electronic health record databases in the US, UK, Germany, Spain, France, South Korea, and Taiwan.

The study included more than 1.1 million individuals who were at least 20 years of age, had no history of cancer, and who used H₂RAs for more than 30 days between January 1986 and December 2020. The cohort included 909,168 new users of ranitidine and 274,831 new users of other H₂RAs.

The crude incidence rate of cancer was 14.30 events per 1000 person-years among ranitidine users and 15.03 events per 1000 person-years for users of other H₂RAs.

After propensity score matching (n=217,406 in each group), the risk of all cancers was similar with ranitidine and other H₂RAs; 18.11 and 17.82 per 1000 person-years, respectively (hazard ratio [HR], 1.04; 95% CI, 0.97-1.13; P =.24). For all cancers excluding nonmelanoma skin cancer, the primary outcome, the risk was similar with ranitidine and other H₂RAs; 15.92 and 15.65 per 1000 person-years, respectively (HR, 1.04; 95% CI, 0.97-1.12).

When the researchers looked at individual cancers, they found no association between ranitidine and an increased risk of leukemia or breast, prostate, lung, colorectal, bladder, liver, pancreatic, stomach, thyroid, uterine, ovarian, esophageal, gallbladder and biliary tract, cervical, or lip/oral cavity/pharynx cancers.

The researchers also looked at the primary outcome, all cancers excluding nonmelanoma skin cancer, across databases and regions. They found no significant differences in risk between the ranitidine and H₂RA groups in the AmbEMR (HR, 1.00; 95%CI: 0.97-1.03) and CUIMC (HR, 0.97; 95%CI, 0.87-1.08) databases. However, ranitidine use was associated with a higher risk of the primary outcome in the SIDIAP (HR, 1.16; 95% CI, 1.01-1.34) and NHIS-NSC (HR, 1.11; 95% CI, 1.02-1.20) databases.

The risk of all cancers excluding nonmelanoma skin cancer was not significantly higher with ranitidine in the primary meta-analysis of results from 4 databases (HR, 1.04; 95% CI, 0.97-1.12) or in the meta-analysis of results across 11 databases (HR, 1.03; 95% CI, 0.99-1.08).  

In addition, a subgroup meta-analysis showed no significant difference in the risk of the primary outcome between ranitidine users and other H₂RA users in the US (HR, 1.00; 95% CI, 0.97-1.03) or Europe (HR, 1.09; 95% CI, 0.99-1.19). However, the risk of the primary outcome was higher among ranitidine users in Asia (HR, 1.09; 95% CI, 1.02-1.18).

“These findings suggest that a history of ranitidine use is not associated with an increased risk of cancer compared with use of other H2 receptor antagonists, but further research is needed on the long-term effects of ranitidine on cancer development,” the researchers concluded.

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

Redispensing unused oral cancer drugs is associated with waste reduction and cost savings, according to research published in JAMA Oncology.

The findings suggest that redispensing unused therapies may improve the affordability and sustainability of cancer treatment, researchers reported. The researchers evaluated the impact of redispensing unused cancer drugs in the multicenter ROAD trial.

The study included 1071 cancer patients in the Netherlands who had a prescription for an oral cancer drug that could be stored at room temperature. Treatments included targeted therapies (56.8%), cytotoxic agents (22.1%), endocrine therapy (13.2%), and immunosuppressants (7.9%).

The drugs were dispensed in sealed packaging with a time-temperature indicator. Patients were instructed to return unused drugs to the pharmacy during planned hospital visits.

Drugs that met quality requirements were redispensed to other patients. Quality requirements included unopened and undamaged packaging, a shelf life of 6 months or more, and drug storage per the summary of product characteristics, measured by a time-temperature indicator.

A total of 13,069 drug packages containing an average of 27 daily doses were dispensed during the study period. Ultimately, 171 patients returned 335 unused drug packages, and 228 of the packages were redispensed. This resulted in a 68.1% reduction in waste when compared to drug disposal. In other words, for every 8 patients receiving oral anticancer drug treatment, redispensing unused drugs enabled waste avoidance for 1 patient.

The quality requirements were met for 73.4% of returned packages. Reasons for returned drugs not meeting the quality standard included opened packaging (77.5%), damaged outer packaging (60.7%), lack of a time-temperature indicator (31.5%), short shelf life (21.3%), and/or temperature breach (10.1%).

Eighteen packages were not redispensed due to reasons other than quality, such as no need for that particular drug or change in stock.

Of the returned drugs, 68.0% were targeted therapies, 18.0% were endocrine therapies, 7.5% were immunosuppressants, and 6.6% were cytotoxic agents. Reasons for the return of drugs included disease progression (47.4%), drug switch (44.8%), discontinuation (34.0%), toxicity (29.4%), and dose adjustments (18.0%).

Redispensing of unused drugs resulted in a mean net annual cost savings of $680 to $1591 USD per patient. Waste reduction through redispensing drugs comprised 2.4% of total drug costs.

The cost savings could be increased by minimizing quality assurance and focusing on subgroups of patients, the researchers noted. “Nevertheless, these findings indicate that redispensing unused drugs has the potential to improve sustainability and affordability in cancer treatment,” they concluded.

The sNDA is supported by data from the phase 1/2 TRIDENT-1 trial (ClinicalTrials.gov Identifier: NCT03093116), which included adult patients with NTRK-positive solid tumors. Findings showed treatment with repotrectinib resulted in clinically meaningful and durable responses in patients with NTRK-positive locally advanced or metastatic solid tumors, including those whose tumors harbor common resistance mutations.

The application also includes data from the phase 1/2 CARE trial (ClinicalTrials.gov Identifier: NCT04094610), which is evaluating repotrectinib in pediatric patients with locally advanced or metastatic solid tumors harboring ALK, ROS1 or NTRK1-3 gene alterations.

Repotrectinib is currently approved under the brand name Augtyro for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer.

“While great advancements have been made over the last decade, patients with NTRK-positive locally advanced or metastatic solid tumors still experience significant unmet needs,” said Joseph Fiore, vice president, Bristol Myers Squibb, and global program lead for Augtyro. “New and effective treatment options that may improve durability of response and address resistance to existing tyrosine kinase inhibitors are critical to helping patients with these aggressive tumors. We look forward to working closely with the FDA on the review of our application for Augtyro for this tumor-agnostic indication and potentially offering patients with NTRK-positive disease a new, durable treatment option.”

The FDA is expected to make a decision on the sNDA on June 15, 2024.

Vitrakvi is a kinase inhibitor indicated for the treatment of adult and pediatric patients with solid tumors that: have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation; are metastatic or where surgical resection is likely to result in severe morbidity; and have no satisfactory alternative treatments or that have progressed following treatment. Patients treated with Vitrakvi may be immunocompromised and therefore at greater risk of serious adverse events if they receive the contaminated product.

The affected product has a lot# of 2114228 and an expiration date of February 29, 2024. The oral solution is packaged in 100mL glass bottles and was distributed nationwide between January 2, 2023 and February 13, 2023. 

The microbial contamination was identified as Penicillium brevicompactum, a type of fungus. Based on cases of invasive disease caused by similar Penicillium species, it is believed that ingestion among patients with immunosuppression may result in invasive fungal infections. At this time, there have been no reports of adverse events related to this recall. Patients who have received the affected product should discontinue use immediately.

Patients and prescribers with questions should contact Bayer Medical Information at 888-842-2937. Adverse reactions should be reported to the FDA’s MedWatch program.