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In a 2022 interview at the World Conference on Lung Cancer, Gerard M. Walls, MB, MRCP, MSc, of Queen's University Belfast in Northern Ireland, summed up the aims of radioimmunotherapy, explaining that "in lung cancer, we're interested in combining novel agents along with radiotherapy [RT] because a lot of our patients aren't able to tolerate chemotherapy at the same time as radiotherapy."

"By using novel, radiosensitizing agents, we hope to avoid the need for [IV] chemotherapy, and actually give these oral ... treatments, along with radiotherapy, to improve the effectiveness, but also keep it very safe for patients so that they are able to tolerate the full treatment, and we're really interested if there's a novel benefit with these drugs in terms of efficacy, and how well the radiotherapy works," he told .

Nitin Ohri, MD, MS, of Montefiore Einstein Comprehensive Cancer Center in New York City, and colleagues, put that approach into practice, testing a strategy of sequential pembrolizumab (Keytruda) and risk-adapted RT, but without chemotherapy, in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). These patients also had a PD-L1 tumor proportion score (TPS) ≥50%.

As the team explained in the study in the, the patients received three cycles of induction pembrolizumab, followed by a 20-fraction course of risk-adapted thoracic RT, followed by consolidation pembrolizumab to complete a 1-year treatment course.

Among the 25 patients, two developed disease progression during induction pembrolizumab, while two others stopped pembrolizumab after a single infusion because of immune-related adverse events (AEs). Still, nearly half exhibited a partial or complete response after induction pembrolizumab, and nearly all were able to get thoracic RT.

Ohri's group reported a 1-year progression-free survival rate of 76% and 1- and 2-year overall survival rates of 92% and 76%, respectively, with common grade 3 AEs of colitis and esophagitis.

"Our de-intensified treatment regimen was tolerated well," the researchers wrote. "Clinical outcomes thus far have exceeded expectations, supporting further investigation of this treatment strategy," and the study results "suggest that omitting chemotherapy may not compromise outcomes for patients with LA-NSCLC with high PD-L1 TPS who are receiving immunotherapy."

SPRINT's estimated study is November 2026. In the meantime, other researchers have advanced a radioimmunotherapy protocol in NSCLC. Here are some of their recent comments:

What's the current status of radioimmunotherapy in the real-world setting, and what's needed to improve the delivery of radioimmunotherapy in NSCLC?

Xiaomei Gong, MD, PhD, of Shanghai Pulmonary Hospital/Tongji University School of Medicine, and colleagues in : Currently, delivery of radiotherapy and PD-1/PD-L1 blockades in the clinical practice is still imprecise, with a limited ability to identify patients who will get survival benefit from immune blockades and radiation treatments or patients who are likely to suffer from adverse effects caused by these modalities.

Predictive biomarkers are in urgent need in order to tailor the treatment strategy. Currently, tumor PD-L1 expression level is the only approved biomarker to drive ICIs [immune checkpoint inhibitors] in clinical practice. PD-L1 is not a perfect biomarker to predict response to PD-1/PD-L1 inhibitors.

It is difficult to obtain enough lung biopsy in some cases; therefore, invasive biomarkers derived from peripheral blood are attractive options compared with tissue-derived biomarkers ... Inflammatory indexes such as high level of baseline neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and low level of lymphocyte to monocyte ratio are reliable indicators of poor survival in advanced NSCLC ... A similar association of NLR with patient survival was also observed in radiotherapy ... Integrating NLR and other known biomarkers has demonstrated better predictive value for immunotherapy.

Which trials have highlighted the potential of radioimmunotherapy in NSCLC, and what are some questions still to be answered?

Jinming Yu, MD, PhD, of Shandong University Cancer Center in China, and colleagues in : Radioimmunotherapy has shown an exciting impact on patients with certain cancers. The trial has laid a framework of adjuvant administration of durvalumab after chemoradiotherapy for patients who are suffering from NSCLC in stage III. The trial showed that 81.8% of patients who received durvalumab [Infinizi] after concurrent chemoradiotherapy had pneumonitis and 59.5% were asymptomatic pneumonitis.

Although the has been quite well-known since its initial description, the underlying mechanisms of how RT influences immune cells and induces abscopal regression of tumor remain unknown. Meanwhile, according to the rarity of the abscopal effect, we should take into account how to amplify the occurrence of this phenomenon so as to expand the beneficial population.

Second, the optimal patterns of radioimmunotherapy largely remain unresolved. The agents, sequence, dose, fractionation, and irradiated sites required further exploration.

What are some of the unique follow-up needs for long-term NSCLC survivors after radioimmunotherapy?

Markus Stana, PhD, Paracelsus Medical University in Salzburg, Austria, and colleagues in : Post-treatment pulmonary function is especially important for long-term survivors. It has been argued that carbon monoxide diffusing capacity (DLCO) may be a better parameter for these lung function changes after RT than forced expiratory volume in one second (FEV1) as it represents the alveolar compartment.

Regarding our study, in the current analysis we can show that DLCO correlates with radiation dosimetry and the incidence of pneumonitis; 112 patients treated for inoperable NSCLC stage III with curative intent were included. Following two cycles of platinum-based induction chemotherapy, all patients received sequential high-dose RT. As of September 2017, patients received durvalumab maintenance therapy for 1 year at a dose of 10 mg/kg within the Austrian early access program.

The clinical endpoints were based on the thresholds jointly published by the European Respiratory Society and the American Thoracic Society. Pre-treatment DLCO of 60% was correlated to the incidence of pneumonitis, whereas the post-treatment DLCO decline of 10% was related to radiation dose.

Patients with a pre-treatment DLCO < 60% had a higher probability of pneumonitis, which could be reproduced in the subgroup of patients who did not receive durvalumab. In these individuals, the decline in DLCO ≥10% depended significantly on the size of the lung volume receiving between 45% and 65% (V65-45%) of the total radiation dose and V20 Total Lung.

The current analysis revealed that DLCO is a predictor for clinically relevant pneumonitis and a monitoring tool for post-treatment lung function as it correlates with radiation dose. From a clinical point of view, peri-treatment lung function testing is indispensable as it helps to optimize radiation treatment planning and predicts pulmonary toxicity.

Read the JCO study here.