Key clinical point: Q-122, a novel nonhormonal oral treatment, significantly improved vasomotor symptoms and was well-tolerated in women with breast cancer (BC) who received oral adjuvant endocrine therapy (ET).

Major finding: After 28 days, Q-122 led to a significantly higher improvement in the mean Vasomotor Symptom Severity Score of moderate and severe hot flushes and night sweats than placebo (−39% vs −26%; P = .018). Q-122 was well tolerated, and most adverse events were mild-to-moderate in severity.

Study details: Findings are from a multicenter, phase 2 study including 131 women with BC who were receiving oral adjuvant ET and were randomly assigned to receive 100 mg oral Q-122 or identical placebo, twice daily for 28 days.

Disclosures: This study was funded by QUE Oncology. The authors declared delivering lectures or receiving honoraria, grant funding, or personal fees from several sources. Two authors declared being current or former employees of QUE Oncology.

Source: Vrselja A et al. Q-122 as a novel, non-hormonal, oral treatment for vasomotor symptoms in women taking tamoxifen or an aromatase inhibitor after breast cancer: A phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2022;400(10364):1704-1711 (Nov 12). Doi: 10.1016/S0140-6736(22)01977-8

Key clinical point: Q-122, a novel nonhormonal oral treatment, significantly improved vasomotor symptoms and was well-tolerated in women with breast cancer (BC) who received oral adjuvant endocrine therapy (ET).

Major finding: After 28 days, Q-122 led to a significantly higher improvement in the mean Vasomotor Symptom Severity Score of moderate and severe hot flushes and night sweats than placebo (−39% vs −26%; P = .018). Q-122 was well tolerated, and most adverse events were mild-to-moderate in severity.

Study details: Findings are from a multicenter, phase 2 study including 131 women with BC who were receiving oral adjuvant ET and were randomly assigned to receive 100 mg oral Q-122 or identical placebo, twice daily for 28 days.

Disclosures: This study was funded by QUE Oncology. The authors declared delivering lectures or receiving honoraria, grant funding, or personal fees from several sources. Two authors declared being current or former employees of QUE Oncology.

Source: Vrselja A et al. Q-122 as a novel, non-hormonal, oral treatment for vasomotor symptoms in women taking tamoxifen or an aromatase inhibitor after breast cancer: A phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2022;400(10364):1704-1711 (Nov 12). Doi: 10.1016/S0140-6736(22)01977-8

Key clinical point: Q-122, a novel nonhormonal oral treatment, significantly improved vasomotor symptoms and was well-tolerated in women with breast cancer (BC) who received oral adjuvant endocrine therapy (ET).

Major finding: After 28 days, Q-122 led to a significantly higher improvement in the mean Vasomotor Symptom Severity Score of moderate and severe hot flushes and night sweats than placebo (−39% vs −26%; P = .018). Q-122 was well tolerated, and most adverse events were mild-to-moderate in severity.

Study details: Findings are from a multicenter, phase 2 study including 131 women with BC who were receiving oral adjuvant ET and were randomly assigned to receive 100 mg oral Q-122 or identical placebo, twice daily for 28 days.

Disclosures: This study was funded by QUE Oncology. The authors declared delivering lectures or receiving honoraria, grant funding, or personal fees from several sources. Two authors declared being current or former employees of QUE Oncology.

Source: Vrselja A et al. Q-122 as a novel, non-hormonal, oral treatment for vasomotor symptoms in women taking tamoxifen or an aromatase inhibitor after breast cancer: A phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2022;400(10364):1704-1711 (Nov 12). Doi: 10.1016/S0140-6736(22)01977-8

Key clinical point: Margetuximab failed to demonstrate a survival advantage over trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer (BC).

Major finding: After a median follow-up of 20.2 months, no benefit in overall survival (OS) was observed with margetuximab vs trastuzumab (hazard ratio [HR] 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab.

Study details: Findings are from the phase 3 SOPHIA study including 536 patients with HER2+ advanced BC who received ≥2 prior anti-HER2 regimens and were randomly assigned to receive chemotherapy with margetuximab or trastuzumab.

Disclosures: This study was supported by MacroGenics, Inc. The authors declared serving as employees, consultants, or on speaker’s bureaus, holding stock options, or receiving honoraria, research funding, or travel or accommodation expenses from several sources, including MacroGenics.

Source: Rugo HS et al  on behalf of the SOPHIA Study Group. Margetuximab versus trastuzumab in patients with previously treated her2-positive advanced breast cancer (SOPHIA): Final overall survival results from a randomized phase 3 trial. J Clin Oncol. 2022 (Nov 4). Doi: 10.1200/JCO.21.02937

Key clinical point: Margetuximab failed to demonstrate a survival advantage over trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer (BC).

Major finding: After a median follow-up of 20.2 months, no benefit in overall survival (OS) was observed with margetuximab vs trastuzumab (hazard ratio [HR] 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab.

Study details: Findings are from the phase 3 SOPHIA study including 536 patients with HER2+ advanced BC who received ≥2 prior anti-HER2 regimens and were randomly assigned to receive chemotherapy with margetuximab or trastuzumab.

Disclosures: This study was supported by MacroGenics, Inc. The authors declared serving as employees, consultants, or on speaker’s bureaus, holding stock options, or receiving honoraria, research funding, or travel or accommodation expenses from several sources, including MacroGenics.

Source: Rugo HS et al  on behalf of the SOPHIA Study Group. Margetuximab versus trastuzumab in patients with previously treated her2-positive advanced breast cancer (SOPHIA): Final overall survival results from a randomized phase 3 trial. J Clin Oncol. 2022 (Nov 4). Doi: 10.1200/JCO.21.02937

Key clinical point: Margetuximab failed to demonstrate a survival advantage over trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer (BC).

Major finding: After a median follow-up of 20.2 months, no benefit in overall survival (OS) was observed with margetuximab vs trastuzumab (hazard ratio [HR] 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab.

Study details: Findings are from the phase 3 SOPHIA study including 536 patients with HER2+ advanced BC who received ≥2 prior anti-HER2 regimens and were randomly assigned to receive chemotherapy with margetuximab or trastuzumab.

Disclosures: This study was supported by MacroGenics, Inc. The authors declared serving as employees, consultants, or on speaker’s bureaus, holding stock options, or receiving honoraria, research funding, or travel or accommodation expenses from several sources, including MacroGenics.

Source: Rugo HS et al  on behalf of the SOPHIA Study Group. Margetuximab versus trastuzumab in patients with previously treated her2-positive advanced breast cancer (SOPHIA): Final overall survival results from a randomized phase 3 trial. J Clin Oncol. 2022 (Nov 4). Doi: 10.1200/JCO.21.02937

Key clinical point: The risk for uterine diseases was significantly increased in premenopausal women with breast cancer (BC) who received tamoxifen as an adjuvant hormone therapy.

Major finding: Compared with patients who did not receive adjuvant hormone therapy, those who received tamoxifen had a significantly higher risk for endometrial cancer (hazard ratio [HR] 3.77; 95% CI 3.04-4.66), endometrial polyps (HR 3.90; 95% CI 3.65-4.16), hyperplasia (HR 5.56; 95% CI 5.06-6.12), and other uterine cancers (HR 2.27; 95% CI 1.54-3.33).

Study details: Findings are from a nationwide, retrospective, longitudinal cohort study including 78,320 premenopausal women with BC who received (tamoxifen only; n = 34,637) or did not receive (n = 43,683) an adjuvant hormone treatment.

Disclosures: This study was supported by a National Research Foundation of Korea grant. The authors declared no conflicts of interest.

Source: Ryu KJ et al. Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment in premenopausal women with breast cancer. JAMA Netw Open. 2022 5(11):e2243951 (Nov 28). Doi: 10.1001/jamanetworkopen.2022.43951

Key clinical point: The risk for uterine diseases was significantly increased in premenopausal women with breast cancer (BC) who received tamoxifen as an adjuvant hormone therapy.

Major finding: Compared with patients who did not receive adjuvant hormone therapy, those who received tamoxifen had a significantly higher risk for endometrial cancer (hazard ratio [HR] 3.77; 95% CI 3.04-4.66), endometrial polyps (HR 3.90; 95% CI 3.65-4.16), hyperplasia (HR 5.56; 95% CI 5.06-6.12), and other uterine cancers (HR 2.27; 95% CI 1.54-3.33).

Study details: Findings are from a nationwide, retrospective, longitudinal cohort study including 78,320 premenopausal women with BC who received (tamoxifen only; n = 34,637) or did not receive (n = 43,683) an adjuvant hormone treatment.

Disclosures: This study was supported by a National Research Foundation of Korea grant. The authors declared no conflicts of interest.

Source: Ryu KJ et al. Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment in premenopausal women with breast cancer. JAMA Netw Open. 2022 5(11):e2243951 (Nov 28). Doi: 10.1001/jamanetworkopen.2022.43951

Key clinical point: The risk for uterine diseases was significantly increased in premenopausal women with breast cancer (BC) who received tamoxifen as an adjuvant hormone therapy.

Major finding: Compared with patients who did not receive adjuvant hormone therapy, those who received tamoxifen had a significantly higher risk for endometrial cancer (hazard ratio [HR] 3.77; 95% CI 3.04-4.66), endometrial polyps (HR 3.90; 95% CI 3.65-4.16), hyperplasia (HR 5.56; 95% CI 5.06-6.12), and other uterine cancers (HR 2.27; 95% CI 1.54-3.33).

Study details: Findings are from a nationwide, retrospective, longitudinal cohort study including 78,320 premenopausal women with BC who received (tamoxifen only; n = 34,637) or did not receive (n = 43,683) an adjuvant hormone treatment.

Disclosures: This study was supported by a National Research Foundation of Korea grant. The authors declared no conflicts of interest.

Source: Ryu KJ et al. Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment in premenopausal women with breast cancer. JAMA Netw Open. 2022 5(11):e2243951 (Nov 28). Doi: 10.1001/jamanetworkopen.2022.43951

Key clinical point: The addition of weekly carboplatin to standard anthracycline-weekly paclitaxel-based neoadjuvant chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC).

Major finding: The rate of pCR was significantly higher in the anthracycline-paclitaxel+carboplatin vs anthracycline-paclitaxel treatment group (51.9% vs 34.2%; odds ratio 2.40; P = .01); however, no significant differences were observed in grade ≥3 hematological toxicities between both groups.

Study details: Findings are from a multicenter study including 247 patients with TNBC who received sequential treatment with anthracycline and weekly paclitaxel with or without weekly carboplatin.

Disclosures: This study was supported by the Italian Ministry of Health. The authors declared receiving personal fees, grants, or non-financial support from several sources.

Source: Dieci MV et al. Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: Propensity-score matching analysis and TIL evaluation. Br J Cancer. 2022 (Nov 17). Doi: 10.1038/s41416-022-02050-8

Key clinical point: The addition of weekly carboplatin to standard anthracycline-weekly paclitaxel-based neoadjuvant chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC).

Major finding: The rate of pCR was significantly higher in the anthracycline-paclitaxel+carboplatin vs anthracycline-paclitaxel treatment group (51.9% vs 34.2%; odds ratio 2.40; P = .01); however, no significant differences were observed in grade ≥3 hematological toxicities between both groups.

Study details: Findings are from a multicenter study including 247 patients with TNBC who received sequential treatment with anthracycline and weekly paclitaxel with or without weekly carboplatin.

Disclosures: This study was supported by the Italian Ministry of Health. The authors declared receiving personal fees, grants, or non-financial support from several sources.

Source: Dieci MV et al. Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: Propensity-score matching analysis and TIL evaluation. Br J Cancer. 2022 (Nov 17). Doi: 10.1038/s41416-022-02050-8

Key clinical point: The addition of weekly carboplatin to standard anthracycline-weekly paclitaxel-based neoadjuvant chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC).

Major finding: The rate of pCR was significantly higher in the anthracycline-paclitaxel+carboplatin vs anthracycline-paclitaxel treatment group (51.9% vs 34.2%; odds ratio 2.40; P = .01); however, no significant differences were observed in grade ≥3 hematological toxicities between both groups.

Study details: Findings are from a multicenter study including 247 patients with TNBC who received sequential treatment with anthracycline and weekly paclitaxel with or without weekly carboplatin.

Disclosures: This study was supported by the Italian Ministry of Health. The authors declared receiving personal fees, grants, or non-financial support from several sources.

Source: Dieci MV et al. Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: Propensity-score matching analysis and TIL evaluation. Br J Cancer. 2022 (Nov 17). Doi: 10.1038/s41416-022-02050-8

Key clinical point: Breast cancer (BC) survivors who were active or moderately active had an ~60% lower risk for mortality compared with those who were insufficiently active.

Major finding: Compared with insufficiently active participants, the risk for mortality was ~60% lower in active (hazard ratio [HR] 0.42; 95% CI 0.21-0.85) and moderately active (HR 0.40; 95% CI 0.17-0.95) participants.

Study details: Findings are from a cohort study including 315 postmenopausal BC survivors who were followed for a minimum of 2 years post-diagnosis.

Disclosures: This study was supported by the US National Cancer Institute. The authors declared no conflicts of interest.

Source: Chen LH et al. Association of physical activity with risk of mortality among breast cancer survivors. JAMA Netw Open. 2022;5(11):e2242660 (Nov 17). Doi: 10.1001/jamanetworkopen.2022.42660

Key clinical point: Breast cancer (BC) survivors who were active or moderately active had an ~60% lower risk for mortality compared with those who were insufficiently active.

Major finding: Compared with insufficiently active participants, the risk for mortality was ~60% lower in active (hazard ratio [HR] 0.42; 95% CI 0.21-0.85) and moderately active (HR 0.40; 95% CI 0.17-0.95) participants.

Study details: Findings are from a cohort study including 315 postmenopausal BC survivors who were followed for a minimum of 2 years post-diagnosis.

Disclosures: This study was supported by the US National Cancer Institute. The authors declared no conflicts of interest.

Source: Chen LH et al. Association of physical activity with risk of mortality among breast cancer survivors. JAMA Netw Open. 2022;5(11):e2242660 (Nov 17). Doi: 10.1001/jamanetworkopen.2022.42660

Key clinical point: Breast cancer (BC) survivors who were active or moderately active had an ~60% lower risk for mortality compared with those who were insufficiently active.

Major finding: Compared with insufficiently active participants, the risk for mortality was ~60% lower in active (hazard ratio [HR] 0.42; 95% CI 0.21-0.85) and moderately active (HR 0.40; 95% CI 0.17-0.95) participants.

Study details: Findings are from a cohort study including 315 postmenopausal BC survivors who were followed for a minimum of 2 years post-diagnosis.

Disclosures: This study was supported by the US National Cancer Institute. The authors declared no conflicts of interest.

Source: Chen LH et al. Association of physical activity with risk of mortality among breast cancer survivors. JAMA Netw Open. 2022;5(11):e2242660 (Nov 17). Doi: 10.1001/jamanetworkopen.2022.42660

Key clinical point: Trastuzumab deruxtecan demonstrated superior survival outcomes compared with trastuzumab emtansine in the second-line setting and also had a manageable safety profile in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: Trastuzumab deruxtecan vs trastuzumab emtansine resulted in a ~36% reduction in the risk for death (hazard ratio 0.64; P = .0037) and the longest reported improvement in progression-free survival (28.8 months vs 6.8 months; nominal P < .0001). The rate of grade ≥3 adverse events was similar with trastuzumab deruxtecan vs trastuzumab emtansine (56% vs 52%).

Study details: Findings are from the phase 3, DESTINY-Breast03 trial including 524 patients with HER2+ metastatic BC who had progressed during or after treatment with trastuzumab and a taxane and were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine.

Disclosures: This study was funded by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daiichi Sankyo, and the other authors reported ties with various sources, including Daiichi Sankyo and AstraZeneca.

Source: Hurvitz SA et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2022 (Dec 7). Doi: 10.1016/S0140-6736(22)02420-5

Key clinical point: Trastuzumab deruxtecan demonstrated superior survival outcomes compared with trastuzumab emtansine in the second-line setting and also had a manageable safety profile in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: Trastuzumab deruxtecan vs trastuzumab emtansine resulted in a ~36% reduction in the risk for death (hazard ratio 0.64; P = .0037) and the longest reported improvement in progression-free survival (28.8 months vs 6.8 months; nominal P < .0001). The rate of grade ≥3 adverse events was similar with trastuzumab deruxtecan vs trastuzumab emtansine (56% vs 52%).

Study details: Findings are from the phase 3, DESTINY-Breast03 trial including 524 patients with HER2+ metastatic BC who had progressed during or after treatment with trastuzumab and a taxane and were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine.

Disclosures: This study was funded by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daiichi Sankyo, and the other authors reported ties with various sources, including Daiichi Sankyo and AstraZeneca.

Source: Hurvitz SA et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2022 (Dec 7). Doi: 10.1016/S0140-6736(22)02420-5

Key clinical point: Trastuzumab deruxtecan demonstrated superior survival outcomes compared with trastuzumab emtansine in the second-line setting and also had a manageable safety profile in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: Trastuzumab deruxtecan vs trastuzumab emtansine resulted in a ~36% reduction in the risk for death (hazard ratio 0.64; P = .0037) and the longest reported improvement in progression-free survival (28.8 months vs 6.8 months; nominal P < .0001). The rate of grade ≥3 adverse events was similar with trastuzumab deruxtecan vs trastuzumab emtansine (56% vs 52%).

Study details: Findings are from the phase 3, DESTINY-Breast03 trial including 524 patients with HER2+ metastatic BC who had progressed during or after treatment with trastuzumab and a taxane and were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine.

Disclosures: This study was funded by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daiichi Sankyo, and the other authors reported ties with various sources, including Daiichi Sankyo and AstraZeneca.

Source: Hurvitz SA et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2022 (Dec 7). Doi: 10.1016/S0140-6736(22)02420-5

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

A version of this article first appeared on Medscape.com.

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

A version of this article first appeared on Medscape.com.

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

A version of this article first appeared on Medscape.com.