In Early Lung Cancer, Immunotherapy Plus Targeted Radiation May Up Response Rate

NEW YORK (Reuters Health) – Patients with non-small-cell lung cancer (NSCLC) may respond more quickly to neoadjuvant durvalumab combined with stereotactic body radiotherapy than to immunotherapy alone, an early industry-funded trial suggests.

“In patients with early lung cancer, combining immunotherapy using an immune-checkpoint inhibitor with a very brief course of focal radiation led to significantly increased probability of a major pathological response, which means killing at least 90% of the tumor cells,” said lead study author Dr. Nasser K. Altorki of Weill Cornell Medicine and New York-Presbyterian, in New York City.

“Results achieved after five weeks of treatment appear similar to those after more prolonged treatment combining immunotherapy with chemotherapy,” he told Reuters Health by email. “These potentially paradigm-changing results, if confirmed in larger trials, would represent a new standard of care.”

The single-center, phase-2 study enrolled 60 adults with potentially resectable early-stage NSCLC (clinical stages I-IIIA) and Eastern Cooperative Oncology Group performance status of 0 or 1 over almost four years.

Half of the patients were randomly assigned to treatment with neoadjuvant durvalumab monotherapy, and half to treatment with neoadjuvant durvalumab plus stereotactic body radiotherapy. After randomization, the study was unblinded.

All patients were given two 60-minute cycles of 1.12 g intravenous durvalumab infusion, three weeks apart. Immediately before the first durvalumab cycle, participants in the combined therapy group also received three consecutive daily fractions of 8 Gy stereotactic body radiotherapy to the primary tumor. Those without systemic disease progression – 26, or 87%, in each group – received surgery.

Two (7%) patients in the monotherapy group had a major pathological response, versus 16 (53%) patients in the combined-therapy group (crude odds ratio, 16.0; p<0.0001), the researchers report in The Lancet Oncology. Eight of the 16 combined-therapy patients with a major pathological response had a complete pathological response.

The second durvalumab cycle was withheld from three (10%) patients in the combined-therapy group due to immune-related adverse events including hepatitis, pancreatitis, fatigue and thrombocytopenia.

Grade-3/-4 adverse events, occurring in five patients in the monotherapy group and in six in the combination group, included hyponatremia in three patients receiving monotherapy and hyperlipasemia in three receiving combined therapy.

No deaths related to treatment or within 30 days of treatment were reported, but two participants in each group had serious adverse events: one pulmonary embolism and one stroke in the monotherapy group, and one pancreatitis case and one fatigue case in the combination group.

Dr. Arya Amini, chief of thoracic radiotherapy at City of Hope in Duarte, California, told Reuters Health by email, “This trial suggests we may have better outcomes for our operable advanced lung cancer patients if we also incorporate some neoadjuvant radiation treatment, with even low doses that could lead to a higher pathologic response rate without compromising toxicity or delaying surgery.”

“I think these findings will not directly change current practice,” said Dr. Amini, who was not involved in the study. “But the results will impact future trial designs and how we think about approaching our operable, locally advanced lung cancer patients.”

“As oncologists treating lung cancer, we are entering an exciting period,” he added. “These complex patients require multidisciplinary care, so I encourage everyone to discuss patients in a multidisciplinary fashion when possible. From a research perspective, I believe we will succeed when all specialties work together to design future trials, and I look forward to seeing where the field of thoracic oncology goes in the next several decades.”

AstraZeneca funded the study. Several authors, including Dr. Altorki, report financial ties to the company.

SOURCE: The Lancet Oncology, online May 17, 2021.

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