Esclusione: il buco nero della ricerca

Si stima che il rischio di cancro al polmone sia fino a tre volte maggiore tra le persone con  HIV. Lo studio retrospettivo dell’Università di Georgetown ha confermato di recente che la prevalenza era maggiore tra coloro che fumavano, avevano una conta di CD4 inferiore (<400) e la carica virale non soppressa.

Le diagnosi erano state fatte quando il cancro era già allo stadio 3 e, in alcuni casi, allo stadio 4. La sopravvivenza maggiore si è registrata tra coloro che hanno seguito la chemioterapia. Ma, purtroppo, in considerazione dell’assenza di studi sulle terapie in fase di studio, si è registrata una sopravvivenza più breve tra le PWH rispetto alla popolazione generale. Ovviamente, si è registrata anche una risposta alla chemioterapia inferiore tra le PWH che avevano già alcune co-morbosità (Tina Roy, MD). La ricerca ha sottolineato anche che vi potrebbero essere fattori biologici specifici  nelle differenze mostrate tra le diverse PWH che hanno partecipato allo studio.

Un altro studio della American Society of Oncology, che ha analizzato i risultati sull’efficacia della chemioterapia (su una coorte di 21 mila persone) , conferma che gli aventi avversi più comuni della chemioterapia tra le PWH erano endocrinologici e neurologici e non vi sono motivi per escluderle dagli studi sui nuovi chemioterapici e sull’immunoterapia (Dr. D. Hsu) in quanto è grave non conoscerne l’efficacia e gli eventi avversi che non dovrebbero essere diversi da quelli registrati nella popolazione generale che ha mostrato risultati migliori in termini di sopravvivenza.

Ci appelliamo alla community affinché anche in Italia si chieda ai ricercatori di esigere l’inclusione delle PWH negli studi verso l’innovatività della terapia oncologica.

People living with HIV are at an increased risk for lung cancer, with some studies estimating risk to be 1.5 to 3-fold higher compared with the general population.

The exact reasons for this increased risk are not entirely clear but may be associated with lower CD4 cell counts, increased viral loads, and an increased prevalence of smoking. Additionally, people living with HIV often have worse survival outcomes for lung cancer.

“This is something that has been appreciated for a long time, but there is a lack of understanding as to why it is the case,” said Tina Roy, MD, of MedStar Georgetown University Hospital in Washington, D.C. “There is not great understanding whether there is a biological reason, if outcomes are different because of immunosuppression, or if it is related to socioeconomic factors or treatment differences among patients who are HIV-positive, who are excluded from important lung cancer trials.”

People living with HIV are often excluded from clinical trials testing new cancer therapies “because of concerns that the treatments may be unsafe for them,” National Cancer Institute researchers noted. This exclusion results in uncertainty and “doctors are less likely to prescribe these newly approved cancer treatments to their patients with HIV.”

Characteristics of HIV-Associated Disease

Two studies presented at this year’s American Society of Clinical Oncology (ASCO) annual meeting turned their attention to HIV and lung cancer in order to add to growing knowledge related to this patient population.

Roy and colleagues conducted a retrospective study to compare the demographic, clinical, pathologic, and therapeutic characteristics of lung cancer among people living with HIV and people without HIV within MedStar Health.

People living with HIV were younger at lung cancer diagnosis (61.8 vs 64.5; P=0.01), more likely to be unmarried, and more likely to have Medicaid insurance compared with people without HIV. In addition, they had a higher number of comorbidities and were more likely to have a history of chronic obstructive pulmonary disease (51% vs 41%; P=0.0476).

Stage at diagnosis and receipt of stage-appropriate treatment was similar between the two groups of patients. However, there was a trend towards worse survival for people living with HIV at all stages of disease, including early-stage disease.

“One important takeaway finding is that when we looked at the subset of patients who were HIV-positive, those patients that had a lower CD4 count had significantly worse overall survival,” Roy said. Specifically, patients with low CD4 counts (<400 cells/mm3) had significantly worse overall survival compared with those with a high CD4 count (P=0.013).

This reflects the importance of ensuring that people living with HIV treated for lung cancer are also very closely followed by an infectious disease team to make sure the HIV remains under control, she added.

“This could point to there being a potential biological difference in those patients that are less immunosuppressed in terms of survival,” Roy said. “We are working at the Department of Microbiology and Immunology at Georgetown to further assess the microenvironment of HIV-positive and HIV-negative patients to gain a better understanding of this.”

Among people living with HIV, there was improved survival among those patients who received chemotherapy (P<0.001) or immunotherapy (P=0.042) compared with those who did not, and worse survival among patients diagnosed with stage III (P<0.001) or stage IV (P<0.001) disease. Among this population, 97 patients were eligible for lung cancer screening per U.S. Preventive Services Task Force (USPSTF) criteria; however, only seven patients were diagnosed with lung cancer through a screening CT scan.

“In combination that highlights that patients that are screened and captured earlier in this disease process, and the ones that are getting treatment, are the ones doing better,” said Roy, who plans to do additional research to further characterize social determinants of health and biological differences among HIV patients diagnosed with lung cancer.

Real-World Outcomes

second study from ASCO added to growing research looking at real-world outcomes of people with HIV and lung cancer treated with immune checkpoint inhibitors (ICIs). Melinda L. Hsu, MD, of University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland, and colleagues conducted a retrospective study of adults diagnosed with lung cancer treated with ICIs from 2015 to 2021 and grouped them into two cohorts by HIV status. Conferma la differenza tra HIVì- e HIV+

They identified 21,259 people, of whom 105 had HIV (median age 61, 81.9% men).

Taken together, these results indicate “that in a large, real-world population, ICIs are both safe and efficacious in people living with HIV with lung cancer,” Hsu said. “This study suggests that we should not withhold ICIs from [this population] for fear of lack of safety or efficacy, and people living with HIV should be included in clinical trials of new and emerging lung cancer treatments.”

By Leah Lawrence