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

Ian T.T. Liu, MD, JD, MPH, from the Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues examined whether cancer drugs granted accelerated approval demonstrate clinical benefit in a cohort study using publicly available data to identify cancer drugs granted accelerated approval from 2013 to 2023.

A total of 129 cancer drug-indication pairs granted accelerated approval were included in the analysis. The researchers found that 63% of the 46 indications with more than 5 years of follow-up were converted to regular approval, and 22% and 15% were withdrawn and remained ongoing after a median of 6.3 years, respectively.

In confirmatory trials, fewer than half (43%) demonstrated a clinical benefit. There was a decrease from 9.9 to 3.6 years in the time to withdrawal; the time to regular approval increased from 1.6 to 3.6 years. Of the 48 drug-indication pairs converted to regular approval, 40%, 44%, 10%, 4%, and 2% were converted based on overall survival, progression free survival, response rate plus duration of response, and response rate and despite a negative confirmatory trial, respectively. Thirty-eight percent of indications were unchanged comparing accelerated and regular approval, while 63% had different indications.

“Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes,” the authors write.

One author disclosed ties to Gilead and serving as an expert witness. The trial was funded by Arnold Ventures.

Abstract/Full Text

More Information

HealthDay News — For patients with completely resected, high-risk cutaneous melanoma, the novel mRNA-based cancer vaccine (mRNA-4157) combined with pembrolizumab results in improved recurrence-free survival (RFS) compared with pembrolizumab alone, 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.

Adnan Khattak, MBBS, from Hollywood Private Hospital in Nedlands, Australia, and colleagues randomly assigned eligible patients with completely resected, high-risk cutaneous melanoma to receive mRNA-4157 in combination with pembrolizumab or pembrolizumab alone (107 and 50 patients, respectively).

The researchers found that recurrence or death was reported in 22.4 and 40% of patients in the combination and monotherapy arms, respectively, at a median follow-up of 101 and 105 weeks. In the combination and monotherapy arms, the 18-month RFS rates were 78.6 and 62.2%, respectively. Protocol-defined statistical significance and clinically meaningful improvement in RFS was seen with the combination versus pembrolizumab, with a 44% reduction noted in the risk for recurrence or death. The number of patients reporting treatment-related grade 3 or higher adverse events was similar between the arms (25 and 18% for combination and monotherapy, respectively); fatigue was the most common mRNA-4157-related grade 3 event.

“Our phase 2b study shows that a neoantigen mRNA vaccine, when used in combination with pembrolizumab, resulted in prolonged time without recurrence or death compared with pembrolizumab alone,” a coauthor said in a statement.

Several authors disclosed financial ties to pharmaceutical companies, including Moderna and Merck, which are jointly developing and commercializing mRNA-4157/V940.

Press Release

More Information

HealthDay News — Adults with atopic dermatitis (AD) have an increased risk for developing melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC), with significantly higher risks seen for moderate-to-severe versus mild AD, according to a study presented at the annual meeting of the American Academy of Dermatology, held from March 17 to 21 in New Orleans.

Margaret Y. Huang, from the Keck School of Medicine at the University of Southern California in Los Angeles, and colleagues examined the risk for developing melanoma, SCC, and BCC among adults with AD in a retrospective cohort study using a claims database for 2007 to 2021. Data were included for 60 million adults aged 18 years or older with and without a diagnosis of AD who subsequently developed melanoma, SCC, or BCC.

The researchers found that adults with AD had significantly higher risks for developing melanoma, SCC, and BCC compared with those without AD (relative risks 1.23, 1.27, and 1.28, respectively) after adjustment for confounding variables. Adults with moderate-to-severe AD had a significantly higher risk for developing melanoma, SCC, and BCC compared with those with mild AD (relative risks, 1.11, 1.25, and 1.17, respectively).

“In conclusion, our findings support an increased risk of melanoma, SCC, and BCC development in adult patients with AD regardless of AD severity,” the authors write. “More mechanistic studies are necessary to understand AD and the development of skin cancers.”

Abstract

More Information

Janssen and AbbVie are voluntarily withdrawing the accelerated approvals of Imbruvica^® (ibrutinib) for mantle cell lymphoma (MCL) in patients who have received at least 1 prior therapy, and for marginal zone lymphoma (MZL) in patients who require systemic therapy and have received at least 1 prior anti-CD20-based therapy, due to requirements related to accelerated approval status granted by the Food and Drug Administration (FDA).

Under the accelerated approval pathway, continued approval of both of these indications was contingent upon verification and description of clinical benefit in confirmatory trials. The phase 3 SHINE study (ClinicalTrials.gov Identifier: NCT01776840) and the phase 3 SELENE study (ClinicalTrials.gov Identifier: NCT01974440) served as confirmatory studies for the MCL and MZL indications, respectively.

In the SHINE study, patients 65 years and older with untreated MCL were randomly assigned to receive ibrutinib or placebo, in combination with bendamustine and rituximab. Results showed that treatment with ibrutinib significantly prolonged progression-free survival (PFS) compared with placebo (80.6 months vs 52.9 months; hazard ratio, 0.75; 95% CI, 0.59-0.96; P =.01); however, overall survival was found to be similar between the groups. The addition of ibrutinib to chemoimmunotherapy was associated with increased adverse reactions.

The randomized, double-blind, placebo-controlled SELENE study compared ibrutinib to placebo in combination with bendamustine and rituximab (BR) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated MZL. According to the Companies, the study did not meet its primary endpoint of PFS. Additional information from the SELENE trial will be presented at a future medical meeting.

Following a review of the data, the FDA concluded that the primary outcomes from these confirmatory studies were considered insufficient to support conversion to full approval.

“We pursued accelerated approvals for MCL and MZL indications for Imbruvica in the US to offer a treatment to patients who at the time had limited therapeutic options,” said Roopal Thakkar, senior vice president, chief medical officer, AbbVie. “While we are disappointed in the outcome of the confirmatory trials for these indications, we remain confident in the benefit/risk profile of Imbruvica for patients living with multiple forms of blood cancer around the world.”

The withdrawal of the MCL and MZL indications does not affect the other approved indications for Imbruvica.

HealthDay News — For asymptomatic average-risk patients, clinicians should start screening for colorectal cancer (CRC) at age 50 years, according to updated guidance from the American College of Physicians (ACP) published online August 1 in the Annals of Internal Medicine.

Amir Qaseem, MD, PhD, from ACP in Philadelphia, and colleagues developed updated guidance for clinicians on screening for CRC in asymptomatic average-risk adults.

The guidance statement included four recommendation statements. In asymptomatic average-risk adults, clinicians should start CRC screening at age 50 years. For average-risk adults aged 45 to 49 years, clinicians should consider not screening and should discuss the uncertainty relating to benefits and harms for this population. In asymptomatic average-risk adults older than 75 years or in asymptomatic average-risk adults with a life expectancy of 10 years or less, clinicians should stop screening for CRC. Selection of a screening test for CRC should be performed by clinicians in consultation with patients based on discussion of the benefits, harms, costs, availability, and frequency and considering patient values and preferences. Selection of a screening test should be between a fecal immunochemical or high-sensitivity guaiac fecal occult blood test every two years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years. Stool DNA, computed tomography (CT) colonography, capsule endoscopy, urine, or serum screening tests should not be used for CRC.

“The updated guidance statement from ACP advocates for reserving screening recommendations for tests and patient populations associated with favorable high-quality benefit-harm assessments. It shifts away from the more-testing-to-more-people approach in other U.S. guidelines,” write the authors of an accompanying editorial.

“The ACP guidance against CT colonography use to screen for CRC represents a step backward, particularly in underserved communities where screening rates are lower and CRC death rates are much higher,” the American College of Radiology wrote in a statement, adding that starting routine screening at age 50 years rather than 45 years “may also hinder recent gains against the nation’s third leading cancer killer. About a third of those who should be screened for CRC can’t or won’t get a colonoscopy. We need more testing options, not fewer.”

Guidance Statement From the American College of Physicians

Editorial (subscription or payment may be required)

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.

HealthDay News — For patients with primary advanced or recurrent endometrial cancer, dostarlimab plus carboplatin-paclitaxel increases progression-free survival vs carboplatin-paclitaxel alone, according to a study published online March 27 in the New England Journal of Medicine.

Mansoor R. Mirza, MD, from Copenhagen University Hospital in Denmark, and colleagues conducted a phase 3, global trial involving patients with primary advanced stage III or IV or first recurrent endometrial cancer who were randomly assigned to receive dostarlimab (500mg) or placebo plus carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by dostarlimab (1000mg) or placebo every 6 weeks for up to 3 years. A total of 494 patients were randomly assigned in a 1:1 ratio; 23.9% had mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors.

The researchers found that in the dMMR-MSI-H population, estimated progression-free survival was 61.4 and 15.7% in the dostarlimab and placebo groups, respectively, at 24 months (hazard ratio for progression or death, 0.28). Progression-free survival at 24 months was 36.1 and 18.1% in the dostarlimab and placebo groups, respectively, in the overall population (hazard ratio, 0.64). Overall survival was 71.3 and 56.0% with dostarlimab and placebo, respectively, at 24 months (hazard ratio for death, 0.64). Severe and serious adverse events occurred more often in the dostarlimab group.

“The progression-free survival benefit in the dostarlimab group did not appear to be consistent across all prespecified subgroups,” the authors write.

Several authors disclosed financial ties to pharmaceutical companies, including GSK, which manufactures dostarlimab and funded the study.

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

The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Citius Pharmaceuticals regarding the Biologics License Application (BLA) for denileukin diftitox for the treatment of patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) after at least 1 prior systemic therapy.

Denileukin diftitox is an engineered interleukin-2 (IL-2)-diphtheria toxin fusion protein. By binding to the IL-2 receptor on the cell surface, the drug is internalized and causes diphtheria toxin fragments to inhibit protein synthesis resulting in cell death.

Denileukin diftitox was previously approved under the brand name Ontak, which was withdrawn from the market in 2014. The product being developed by Citius under the proposed brand name Lymphir is a reformulation of Ontak.

The BLA submission included data from a phase 3 trial (ClinicalTrials.gov Identifier: NCT01871727) that assessed the safety and efficacy of the reformulated product in patients with recurrent or persistent CTCL. Sixty-nine patients were included in the primary efficacy analysis set. Findings showed the treatment was considered efficacious with an objective response rate (primary endpoint) of 36.2% (95% CI, 25.0-48.7%; 25 patients out of 69). Adverse events were consistent with those previously seen in studies with Ontak.

While no efficacy or safety issues were raised in the CRL, the FDA is requiring the Company to “incorporate enhanced product testing, and additional controls.”

“We intend to provide additional data and remain fully engaged with the FDA as we continue to work toward approval,” said Leonard Mazur, Chairman and CEO of Citius. “We remain confident in the potential of Lymphir to become an important addition to the treatment landscape for patients with relapsed or refractory CTCL and make a meaningful difference in their lives.”

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

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).

Treatment with antibody-drug conjugates may increase the risk of certain adverse events (AEs) in patients with cancer, according to a meta-analysis published in JNCI Cancer Spectrum.

Researchers found that antibody-drug conjugates, when compared to other cancer treatments or placebo, were associated with an increased risk of hepatic, gastrointestinal, ocular, and other AEs.

This meta-analysis included 10,075 patients treated in 20 randomized, phase 2-3 trials comparing antibody-drug conjugates to other treatments or to placebo.

The studies enrolled patients with breast cancer (n=6), lymphoma (n=5), small cell lung cancer (n=3), acute lymphoblastic leukemia (n=1), gastric cancer (n=1), glioblastoma (n=1), mesothelioma (n=1), renal cell carcinoma (n=1), and ovarian cancer (n=1).

In 2 of the studies, the control intervention was placebo. In the remaining 18 studies, the control treatment was an unconjugated antibody, hormone therapy, or cytotoxic/targeted therapy.

In 15 studies, an antibody-drug conjugate was evaluated alone. In 7 studies, it was combined with other anticancer agents. The antibody-drug conjugates studied were trastuzumab emtansine (n=5), brentuximab vedotin (n=4), rovalpituzumab tesirine (n=2), inotuzumab ozogamicin (n=2), trastuzumab deruxtecan (n=1), depatuxizumab mafodotin (n=1), anetumab ravtansine (n=1), AGS-16C3F (n=1), IMGN901 (n=1), mirvetuximab soravtansine (n=1), and sacituzumab govitecan (n=1).

Results

There were no significant differences in the risk of high-grade AEs between patents who received antibody-drug conjugates and patients who did not. However, there were a range of all-grade AEs that were more common among patients who received antibody-drug conjugates.

The researchers identified 4 “clinically relevant” treatment-related AEs of any grade that were significantly more likely for patients who received antibody-drug conjugates. They were fatigue, anorexia, nausea, and sensory neuropathy, as seen in the table below.

There was no increased risk of cardiovascular AEs or renal AEs among patients who received antibody-drug conjugates. However, there was an increased risk of ocular, hepatic, gastrointestinal, and other AEs.

The all-grade AEs that were significantly more likely among patients receiving antibody-drug conjugates were:

• Thrombocytopenia (OR, 2.07; 95% CI, 1.00-4.30)
• Increased alanine aminotransferase (OR, 2.51; 95% CI, 1.84-3.40)
• Increased aspartate aminotransferase (OR, 2.83; 95% CI, 2.04-3.93)  
• Cataracts (OR, 3.92; 95% CI, 1.52-10.13)
• Eye pain (OR, 9.54; 95% CI, 2.64-34.46)
• Photophobia (OR, 6.84; 95% CI, 2.26-20.67)
• Blurred vision (OR, 3.12; 95% CI, 1.02-9.55)
• Epistaxis (OR, 2.45; 95% CI, 1.50-4.01)
• Abdominal pain (OR, 1.29; 95% CI, 1.01-1.66)
• Upper abdominal pain (OR, 1.53, 95% CI, 1.23-1.89)
• Dry mouth (OR, 4.46; 95% CI, 2.56-7.78)
• Vomiting (OR, 1.32; 95% CI,1.01-1.74)
• Gingival bleeding (OR, 6.50, 95% CI, 2.80-15.12)
• Headache (OR, 1.49; 95% CI,1.24-1.79)
• Peripheral motor neuropathy (OR, 3.91; 95% CI, 1.14-13.42).

Several AEs were less likely to occur among patients receiving antibody-drug conjugates. These were hot flashes (OR, 0.57; 95% CI, 0.37-0.88), febrile neutropenia (OR, 0.46; 95% CI, 0.22-0.96), leukopenia (OR, 0.47; 95% CI, 0.29-0.77), lymphopenia (OR, 0.69; 95% CI, 0.48-0.98), and neutropenia (OR, 0.56; 95% CI, 0.31-1.01).

“To the best of our knowledge, this is the first study to comprehensively compare the tolerability of ADC [antibody-drug conjugate]-based regimens with other standard treatments across multiple malignancies,” the researchers wrote. “While our results provide valuable information for clinicians to balance the benefits and risks of treatment options in their decision-making, it is crucial to consider the limitations of our study, particularly the heterogeneity of included studies, when applying these findings to clinical practice.”

Disclosures: One of the study authors declared affiliations with Merck. Please see the original reference for a full list of disclosures.

Reference

Suzuki Y, Zhou S, Ota Y, et al. Toxicity profiles of antibody drug conjugates for anticancer treatment: A systematic review and meta-analysis. JNCI Cancer Spec. Published online September 26, 2023. doi:10.1093/jncics/pkad069

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)

Anlan Cao, MBBS, from Yale University in New Haven, Connecticut, and colleagues evaluated the effect of a 6-month aerobic exercise intervention on CIPN among women treated for ovarian cancer. The analysis included 134 participants in the Women’s Activity and Lifestyle Study in Connecticut (65 controls).

The researchers found that at 6 months, the self-reported CIPN score was 1.3 points lower in the exercise intervention arm (95% CI, −2.3 to −0.2) vs an increase of 0.4 points in the attention control arm (95% CI, −0.8 to 1.5). The between-group difference was −1.6 points (95% CI, −3.1 to −0.2). Among participants with CIPN symptoms at baseline, the point estimate was larger (−2.0; 95% CI, −3.6 to −0.5).

“While replication of the findings in other studies is warranted, incorporating referrals to exercise programs into standard oncology care could reduce CIPN symptoms and increase quality of life in patients with ovarian cancer,” the authors write.

Abstract/Full Text

Afami-cel is an autologous T-cell therapy designed to target cancer cells in solid tumors expressing melanoma-associated antigen A4 (MAGE A4), a protein highly expressed in synovial sarcoma. The BLA submission included data from cohort 1 of the single-arm, open-label phase 2 SPEARHEAD-1 study (ClinicalTrials.gov Identifier: NCT04044768). 

The study evaluated the efficacy and safety of a single intravenous infusion of afami-cel in HLA-A*02 eligible and MAGE-A4 positive patients with advanced synovial sarcoma, or myxoid/round cell liposarcoma, after receiving lymphodepleting chemotherapy. Study participants had received a median of 3 prior lines of systemic therapy (range, 1-12). The primary endpoint was overall response rate (ORR).

Findings showed the ORR was approximately 39%; median duration of response was approximately 12 months. Median overall survival was reported to be about 17 months for afami-ce-treated patients compared with historical outcomes of less than 12 months for patients who received 2 or more prior lines of therapy. Seventy percent of patients who responded to afami-cel were alive 2 years post treatment. 

“The FDA’s acceptance of the BLA submission brings us one step closer to redefining treatment for people with synovial sarcoma,” said Adrian Rawcliffe, Adaptimmune’s CEO. “Our franchise has great potential and, if approved, we have the capabilities and the capital to launch afami-cel – the first engineered T-cell therapy on the market for a solid tumor cancer.”

A Prescription Drug User Fee Act target date of August 4, 2024 has been set for the application.

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.

HealthDay News — Artificial intelligence (AI)-based computer-aided detection (CAD) software improves the detection of actionable lung nodules on chest radiographs, without increased false-referral rates, according to a study published online February 7 in Radiology.

Ju Gang Nam, MD, PhD, from the Artificial Intelligence Collaborative Network at the Seoul National University Hospital and College of Medicine in South Korea, and colleagues examined whether commercial AI-based CAD software can improve the detection rate of actionable lung nodules on chest radiographs in a single-center study. Participants who underwent chest radiography between July 2020 and December 2021 were enrolled and randomly assigned into an AI group and non-AI (control) group (5238 to each group). Each radiograph was interpreted by one of three radiologists with 13 to 36 years of experience.

The researchers found that the trial met the predefined primary outcome, with an improved detection rate of actionable nodules in the AI vs non-AI group (0.59 vs 0.25%; odds ratio, 2.4). For malignant lung nodules, the detection rate was higher in the AI than non-AI group (0.15 vs 0.0%). Similar false-referral rates were seen for the AI and non-AI groups (45.9 vs 56.0%); positive-report rates were also similar between the groups (2.3 vs 1.9%).

“The improved detection rate of actionable lung nodules with a similar false-referral rate suggests that using AI-based CAD may improve lung cancer diagnosis without imposing an additional radiation hazard,” the authors write.

Several authors disclosed financial ties to the medical device industry.

Abstract/Full Text

Editorial