Using radiotherapy to convert immunologically “cold” tumours into “hot” ones does not enhance the efficacy of checkpoint inhibitors in metastatic non-small cell lung cancer, Australian research shows.
No difference in efficacy or toxicity was seen in NSCLC patients who had radiotherapy around the time of starting treatment with anti-PD- 1 immunotherapy compared to patients who did not receive radiotherapy, a retrospective review by Victorian oncologists found.
Clinicians from Monash Health and the Alfred Hospital, Melbourne compared the outcomes of 269 patients with metastatic NSCL treated with pembrolizumab and nivolumab at three centres between 2016 and 2019.
The median age of the patients was 70 years, 63% were male, 60% were smokers, and 65% had adenocarcinoma histology. Almost all (86%) had at least one line of prior therapy.
More than a third (38%) of patients received radiotherapy within three months of starting immune checkpoint inhibitors or during treatment. Most received conventional hypofractionated with the intent of symptom control.
After a median follow up of 19.4months following the start of anti-PD1 therapy, there were no significant differences in any of the efficacy outcomes of response rates, progression-free survival (PFS), and overall survival (OS).
The median PFS was 3.0 months for patients who received radiotherapy vs 2.0 months for those who did not. The median OS was 9.0 months fr both groups.
In terms of toxicity there were no differences in overall rates of treatment-related adverse events between the two groups, with about 20% of patients experiencing TRAEs of any grade.
For high-grade TRAEs (grade 3 or higher) the rates were 8% in the immunotherapy-only group and 13% in the patients who also received radiotherapy (difference not significant).
Pneumonitis was the most common adverse event, and rates of grade 3 or higher pneumonitis were similar (2%) for both groups. Dermatitis adverse events were numerically higher in the radiotherapy-treated patients (2% vs 1%) but the difference was not significant.
The study investigators, led by Dr Evangeline Samuel and Dr Sagun Parakh, said the findings failed to support the hypothesis of improved survival using combined radiotherapy and immunotherapy, but did provide reassuring findings on toxicity, especially pneumonitis.
The lack of effect with additional radiotherapy might be due to variables such as the dose, schedule, and timing of treatment as well as size of treatment field needed to elicit an effective anti-tumour immune response, they suggested.
“The treatment paradigm of NSCLC is rapidly evolving, with immunotherapy becoming the cornerstone of treatment in patients with NSCLC with no driver mutations,” they wrote.
“There is strong rationale in combining radiotherapy and immune checkpoint inhibitors to improve response rates and to overcome resistance to checkpoint inhibitors by converting immunologically “cold” tumours into “hot” tumours. However, further research is needed to determine the optimum sequence of radiotherapy in relation to checkpoint inhibitors,” they concluded.
The findings are published in Clinical Lung Cancer.