New research from Flinders University suggests that patients whose progressive disease comes from existing lesions have better survival than patients with new lesions.
It turns out new is not always better, especially when it comes to progressive disease in non-small cell lung cancer.
The quest for a more standardised assessment of solid tumours was greatly assisted by the revision of the Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1) guidelines. But limitations still exist, like the fact that the guidelines do not consider lesion type or heterogeneity when considering disease progression. This is a significant oversight when you consider that previous research has linked the development of new lesions or a mix of new and old lesions with poorer survival outcomes.
A modified progressive disease classification has since been put forward, but the suitability of this system in patients with non-small cell lung cancer who undergo chemoimmunotherapy has yet to be fully explored. Now, the results of a new Australian study suggest patients treated with chemotherapy and chemoimmunotherapy have different associations between the type of progressive lesions and post-progression survival time.
“If we know which patients are at higher risk after progression, we can tailor follow-up and consider different treatment strategies sooner,” said Ms Yuan Gao, a research officer from the College of Medicine and Public Health at Flinders University and lead author of the new research.
The researchers pooled data from four randomised clinical trials where patients with advanced NSCLC received either chemoimmunotherapy (atezolizumab and chemotherapy with optional bevacizumab) or standard treatment (chemotherapy with or without bevacizumab) to explore the potential associations between different types of progressive lesions, treatments and post-progression survival.
There were 2363 NSCLC patients included in the combined analysis. A greater proportion of these patients received chemoimmunotherapy (1437, 60.8%) compared to chemotherapy (926, 39.2%). Existing lesions were the most common progressive lesion type (43%), ahead of new lesions alone (31%) and the combination of existing and new lesions (26%). There was a similar proportion of patients receiving chemoimmunotherapy and chemotherapy in each of the lesion progression groups.
The researchers found an association between the progressive lesion type and post-progression survival. Patients with progressive disease of only existing lesions had the longest median progression-free survival (9.9 months), ahead of new lesions only (7.3 months) and both existing and new lesions (5.6 months).
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This association remained when considering the treatment the patient received, with a more noticeable association in the chemotherapy group compared to the chemoimmunotherapy group. For patients who received chemoimmunotherapy, the median post-progression survival was 8.8 months for existing lesions, 7.2 months for new lesions and 5.8 months for existing and new lesions. For individuals receiving chemotherapy, median post-progression survival was 11.0 months for patients with existing lesions, 7.6 months for patients with new lesions and 4.9 months for patients with both new and existing lesions.
“People whose cancer comes back with new tumours have a much poorer outlook than those whose existing tumours re-grow. And if both happen – old tumours grow and new ones appear – that’s the worst scenario,” said Michael Sorich, the paper’s senior author and a professor of clinical pharmacology from the College of Medicine and Public Health at Flinders University.
“These differences are significant because they show that not all progression is equal. Understanding this can help doctors and patients make better decisions about what to do next.”
The researchers suggested the differences in survival could be explained by differences in the tumour microenvironment, given that existing and new lesions develop from separate biological contexts.
“[The] prognostic difference might be also explained by exhibiting dissociated response. Control of metastasis or growth in existing lesions may reflect treatment efficacy. Patients with progression of existing lesions or new lesions might still benefit from therapy, potentially exhibiting [a] dissociated response, where lesion progression coexists with tumour shrinkage (i.e., existing lesions shrinkage when developing new lesions),” they wrote in Cancer Letters.
“Differences in post-progression survival across lesion-type subgroups likely reflect variation in disease biology and aggressiveness, potentially influenced by prior treatment exposure. Immunotherapy’s distinct response/progression patterns may contribute to heterogeneity between treatment groups. The underlying mechanisms are uncertain and warrant further investigation.”
