Abstract
The war in Ukraine is disrupting routine patient care, clinical trials, and basic cancer research—with potentially dire consequences. Physicians and researchers are helping patients as best they can, but cancer mortality is expected to rise in the country, and the impact on research could slow medical progress.
In a typical year, about 100,000 people in Ukraine die from cancer—but this is not a typical year. With war raging throughout much of the country, oncologists are warning about the increased death rates that disturbances to routine patient care, clinical trials, and basic cancer research could bring.
“War is a disaster for all people, especially cancer patients,” said Oleksandr Dudnichenko, MD, of V.T. Zaitsev Institute of General and Emergency Surgery in Kharkiv.
“We try to do everything possible to ensure that patients continue their treatment,” he said. Despite relentless bombardments and shortages of essential medicines, that means physicians are attending to any patients who have stayed in conflict-torn cities in eastern, central, and southern Ukraine. They are also assisting with patient transfers to clinics in safer parts of western Ukraine and, when possible, to hospitals in nearby countries or further afield.
But invariably, many patients will miss appointments, forgo essential treatments, skip screenings, or possibly never see an oncologist again, cautioned Richard Sullivan, MD, PhD, codirector of the Centre for Conflict & Health Research at King's College London, UK. “We know from previous refugee crises that many cancer patients are lost—they simply do not present with their symptoms once they become refugees,” he said during a recent Web broadcast focused on cancer and the war.
What's more, those who never leave often have trouble maintaining treatment because, as Sullivan pointed out: “Even if the war stopped tomorrow, it's going to take between a year and a year and a half to rebuild cancer care in Ukraine.”
At Ukraine's National Cancer Institute (NCI) in Kyiv, patients are still receiving life-saving treatment, albeit from the relative safety—and discomfort—of the hospital's basement, which is serving as a bomb shelter. However, treatment options are more limited than before Russia attacked.
Cancer geneticist Mariia Inomistova, PhD, ordinarily helps design personalized dendritic cell vaccines for patients there. She also provides molecular diagnostic testing, mostly for children with pediatric tumors, to identify targeted drug therapies. However, Inomistova, like many others on her team, fled the Ukrainian capital. Others, including her laboratory leader, are stuck in their Kyiv-area homes, unable to cross through battle zones to reach the hospital.
Yet physicians and researchers are helping patients as best they can. For example, Inomistova, now in southern Poland, is translating medical records from Ukrainian to English for those fortunate enough to receive cancer care abroad. Mariia Kukushkina, MD, a melanoma specialist from Ukraine's NCI who is temporarily residing in Lviv, is offering telemedicine consultations for anyone with skin cancer who needs assistance. “It's very difficult for patients to find specialists nowadays,” she said. “So, I try to connect these patients with the right doctor.”
Many displaced patients have found oncologists in Poland, Romania, Slovakia, and other neighboring countries. Others have been evacuated to hospitals in Spain, the UK, the United States, Canada, and elsewhere. But an untold number of Ukrainian patients—including participants in clinical trials that could be halted, disrupted, or delayed because of the war—have stayed behind.
One is Iryna Kozeretska, PhD, a geneticist at the National Antarctic Scientific Center of Ukraine in Kyiv. Kozeretska enrolled in a phase II clinical study last year after finding a cancerous lymph node linked to her ongoing battle with breast cancer. When the war started, she moved 210 miles west to Rivne, where she has been able to receive shipments of her experimental treatment, a selective estrogen receptor degrader (SERD) called camizestrant (AZD9833; AstraZeneca).
Kozeretska's regular bimonthly checkup is approaching, but because of family obligations and threats of military attacks, she can't return to the Kyiv City Clinical Oncology Center to see her doctors. “I would like to,” she said, “but it's absolutely impossible.”
Unable to find a trial investigator in Rivne to draw blood and perform CT scans, she is looking for a participating study site in Poland to continue her care and help ensure that the clinical study of camizestrant operates with minimal gaps in data collection.
Despite the best efforts of patients, clinicians, and industry sponsors, cancer drug trials will be impacted nonetheless, with ripple effects throughout the global oncology research ecosystem. That's because Ukraine—with its skilled medical workforce, centralized health care system, and large population of treatment-naïve patients—is home to hundreds of cancer trials, with late-stage multinational studies involving therapies for breast and lung cancers being the most common.
Most companies have halted recruitment of new participants in Ukraine for these trials while they try to address the needs of patients already enrolled.
Roche, for instance, has ongoing trials of the investigational SERD giredestrant, the PI3Kα inhibitor inavolisib, the anti-TIGIT therapy tiragolumab, and several bispecific antibody drugs—along with studies of approved therapies for novel indications—with sites in Ukraine. “The situation for those patients is currently very challenging,” said Nathalie Meetze, a Roche spokesperson, “and we are actively working on solutions to ensure continued access to treatment for these patients, including [those who] have left Ukraine and moved to other countries.”
One silver lining of the conflict for patients with cancer: Some drugs for which Ukrainians have had to pay out of pocket before the war are available for free thanks to donations from pharmaceutical companies. “The quantity of these drugs is very limited,” Kukushkina said, but at least it's one good thing to happen for her patients. “It sounds very strange, but it's true.” –Elie Dolgin