The addition of durvalumab after chemoradiation (CRT) in unresectable stage 3 non-small cell lung cancer (NSCLC) can be safely delivered in elderly patients ≥70 years with comparable improvement in overall survival (OS), as compared with younger patients. Physician’s Weekly speaks with author Dr. Adrian Sacher (Princess Margaret Cancer Centre, Toronto, ON, Canada) about this analysis presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, which was held virtually 4-10 June, 2021 [1].

The increased toxicity associated with CRT followed by durvalumab weighs heavily in considering the clinical benefit of treatment options in elderly NSCLC patients, but evidence to support this concern is lacking. Accordingly, CRT followed by durvalumab in elderly patients is likely underutilized despite the demonstrated superiority of this approach in the overall population. Curative treatments should be pursued, as indicated in the guidelines, yet many centers deviate based on concerns of frailty in elderly patents.

The single center study reviewed all stage 3 NSCLC patients treated with CRT at the Princess Margaret Cancer Center between 2018 and 2020 (n=115). Patients were sorted by age: <70 years (n=71), ≥70 years (n=44). Endpoints evaluated were treatment patterns, toxicity, progression free survival (PFS) and overall survival (OS). Baseline characteristics, including fitness and PD-L1 expression, were similar. The chemotherapy regimens (platinum in combination with etoposide, paclitaxel or pemetrexed), dose intensity (97% vs 97%) and percentage of planned cycles received (91% vs 96%) were similar. There were 2 treatment-related deaths from CRT among the younger cohort and none in the elderly patients.

After completing CRT, 75% of elderly and 72% of young patients received consolidation durvalumab. The median time to starting durvalumab was 43 days in the elderly and 37 days in young patients (P=0.19). The incidence of grade ≥3 immune-related adverse events was 9% in elderly patients compared to 6% in younger patients (P=0.68), and they were at least as likely to complete durvalumab treatment (30% in elderly vs 24% in younger patients; P=0.22). Median PFS was similar between elderly and young patients (17.9 vs 10.6 months respectively; P=0.07), even after adjusting for the CCI (HR 0.60; P=0.07). The OS rates were nearly identical (P=0.93), at 77% both groups.

Although this was a single-center study, with relatively few patients, the data certainly indicate that CRT followed by durvalumab can be safely delivered in elderly patients ≥70 years with comparable outcomes. There was even a non-significant trend towards better PFS in elderly patients. The researchers conclude that elderly patients are often undertreated.

Physician’s Weekly spoke with Dr. Sacher to understand the implications of the team’s findings:

Unmet need?

“’We initiated the study originally because we were very interested in whether elderly patients both benefited as much as your average patient from chemo-radiotherapy and durvalumab for stage 3, NSCLC as well as if they were at higher risk for adverse events.

The background on this is that most of our lung cancer patients are in older age categories. One thing that we have been worried about is, as we develop newer and better treatments, is that elderly patients might be at higher risk of side effects. Alternatively, they might be undertreated or might not be offered the optimal treatment out of concern that they might not tolerate it as well as a younger patient.

Therefore, we investigated this question in a cohort of stage 3 NSCLC patients treated at our institution looking at both outcomes in terms of progression-free survival and overall survival as well as side effects from treatment, both the chemo radiotherapy part of treatment, which is the old standard of care, as well as the durvalumab consolidation, which is the newer part that has recently started to be utilized after the PACIFIC study. What we found was that, in general, elderly patients were not at higher risk for really severe adverse events especially from the immunotherapy part, the new part of treatment. There was a trend towards a slightly higher risk of hospitalization for infections with the chemoradiotherapy, part of the older part of treatment. We also found that elderly patients derive just as much benefit as younger patients from this treatment.

Our take home point is that for elderly patients with stage 3 non-small cell lung cancer, that we would strongly advocate that they receive chemoradiotherapy followed by durvalumab. Going forward, we will try not to use age alone as a reason to exclude someone from receiving the optimal treatment for a stage three non-small cell.”

Will these data change practice?

“I think it is gonna give a lot of practitioners more comfort. And I think too, it may help to push practitioners that might hesitate about giving chemo radiotherapy and immunotherapy to their elderly patients, to at least think twice about not giving it and make sure that they have a really strong rationale other than just the patient being elderly.”

There is a non-significant trend towards better PFS, how should we take that going forward?

“I am always very cautious about over-interpreting non-significant trends, but I think what it tells us is that, and the way that I would interpret this is, at the very least elderly patients are not doing worse. And they are not being kind of knocked out of the running because they are either not benefiting from treatment or they are having really bad side effects. Patients are getting the same benefit, whether elderly or not, and that kind of behooves you to try to give that benefit to every patient. Part of the genesis of this study was that there might be a bit of a well intentioned nihilism such that elderly patients might preferentially receive palliative treatment as opposed to a more aggressive curative approach. I hope that the study results kind of give people a bit of comfort that they are doing the right thing by giving their elderly patients the most aggressive treatment.”

Next steps?

“We are looking to validate these findings in a multi-center fashion. I suspect we will see the same outcomes but I think it is important to look at this type of real-world evidence, especially when it comes to elderly patients, because there are fewer elderly patients on randomized trials generally, and the ones that are on usually are not representative of your average elderly patient.

The last thing that I would say is that I think this abstract really supports the idea of giving the best possible treatment to our elderly patients with stage three disease. I think we are going to need to ask similar questions in even earlier stage lung cancer, where we are now seeing data suggesting that either neoadjuvant chemo immunotherapy or adjuvant immunotherapy potentially improves the chance of cure. I think this question is probably not only relevant for stage three, but one that we are going to need to kind of look at even at earlier stages in the near future.”

  1. Ryan MI et al. Elderly patients with unresectable stage 3 NSCLC treated with definitive chemoradiation with or without durvalumab: Safety and outcomes. DOI: 10.1200/JCO.2021.39.15_suppl.8547 Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021) 8547-8547.