Overcoming Treatment Barriers With Adjuvant Durvalumab in Unresectable Stage III NSCLC

Because of the survival benefit demonstrated in the phase 3 PACIFIC trial (NCT02125461) with adjuvant durvalumab (Imfinzi) post chemoradiation in patients with stage III non–small cell lung cancer (NSCLC), the approach has become a standard of care, according to Benjamin H. Kann, MD, who added that factors like toxicity and patient hesitancy are existing barriers to treatment that may be overcome with the institution of prescheduled follow-up visits, a strong support system, and early discussions detailing the journey to come.

Updated data from the trial presented during the 2021 ASCO Annual Meeting showed that the median overall survival (OS) with adjuvant durvalumab was 47.5 months (95% CI, 38.1-52.9) vs 29.1 months (95% CI, 22.1-35.1) with placebo (HR, 0.72; 95% CI, 0.59-0.89). The median progression-free survival (PFS) with the immunotherapy vs placebo was 16.9 months (95% CI, 13.0-23.9) vs 5.6 months (95% CI, 4.8-7.7), respectively (HR, 0.55; 95% CI, 0.45-0.68). These data were consistent with findings from the primary analyses of the trial.

“We tend to inundate our patients with information. Many do not have medical backgrounds and are trying to juggle all this information and keep track of it. When they have other preexisting conditions, they may have a whole slew of other appointments with other types of practitioners, and this can be a real challenge,” Kann said. “Having constant reminders about appointments, scheduling, a broad overview of what they are doing for treatment, and continually assessing their understanding of what the next steps are in [their journey], can be helpful and can sometimes prevent things from falling through the cracks.”

In an interview with OncLive^®, Kann, a physician at the Dana-Farber Cancer Institute, and assistant professor of Radiation Oncology at Harvard Medical School, discussed the significance of the PACIFIC trial in patients with stage III NSCLC, existing barriers to treatment, and shared strategies to overcome common challenges faced in clinical practice.

OncLive^®: Could you provide an overview of the PACIFIC study and the data that have been reported from that research?

Kann: PACIFIC was essentially one of the first studies to explore the use of adjuvant immunotherapy in the non-metastatic cancer setting, specifically for [patients with] locally advanced lung cancer. [The study] looked at patients who had received chemoradiation who were then randomized to receive either placebo or adjuvant durvalumab, a PD-L1 inhibitor. This was an exciting study in that a PFS and OS benefit was demonstrated in the patients who received the adjuvant immunotherapy.

Based on the OS advantage observed with the PACIFIC regimen, what are some best practices to ensure that patients not only receive durvalumab after chemoradiotherapy as opposed to other treatments, but that they also stay on the treatment?

[We need to ensure] that all patients have a pre-scheduled follow-up for when they finish their chemoradiation; we usually like to get restaging scans within 1 month afterward. Additionally, we need to educate [patients from the beginning] that their treatment is not going to only consist of chemoradiation, but that it is now standard of care for them to receive adjuvant therapy for up to 1 year. Giving patients the broad overview up front helps them conceptualize and set their expectations for what is to come.

Are any challenges faced with this approach?

Something that can happen on chemoradiation is that patients can get worn out. [They can] develop adverse effects [AEs]. We see [toxicities] like esophagitis, changes in their respiratory status, as well as just feeling tired. [Because of this,] toward the end of treatment, [patients] are not very excited about going on to [yet] another treatment for another year. That can be a barrier.

It is also important to set expectations around the AEs of chemoradiation [and to let patients know] that most of them do resolve over the course of a few weeks after their treatment is over. Again, [we must ensure] that we have a follow-up [appointment] set up with them for about 1 month after [completing their treatment]; at [that] point, they are often in a better place and are more amenable to thinking about next steps in terms of more treatment.

Regarding toxicity, what are some strategies for managing common AEs like pneumonitis?

Pneumonitis is the most common AE we see, and we do know that there is a bit of an increased risk of that with adjuvant durvalumab compared with just chemoradiation alone. [This effect] is something that we see [often], and the first thing we do when a patient comes in, is we always want to make a thorough assessment of their symptoms. [We do a] physical exam to rule out any other types of etiologies for shortness of breath, and we perform a computed tomography scan. If it does look like [the pneumonitis was induced by] chemoradiation and/or immunotherapy, we will consider steroids as our mainstay of treatment.

Obviously, we must have a discussion with medical oncology at that point [to discuss] the risks and benefits of [using] steroids in conjunction with immunotherapy because we know there are interactions there. Generally, a course of steroids will resolve [those] symptoms.

Is there an optimal time for patients to undergo scans after chemoradiotherapy is completed?

There is a range, but somewhere between 2 and 4 weeks after treatment is reasonable.

Are there any patients for whom you would not utilize chemoradiation? What factors do you consider to inform that decision?

Generally, that will come up in situations where the patient has many preexisting comorbidities or a very poor performance status. [Those would be] patients who have preexisting cardiovascular disease, kidney disease, or very poor lung function. [We may] drop the chemotherapy, modify the chemotherapy, or [use] radiation alone if the patient is very frail and it is felt that they are just not going to be able to tolerate the chemotherapy. Even more rarely than that, we might go with just systemic therapy, and not radiation. [However,] that is usually only done in situations where a patient has extremely severe underlying lung disease and we believe that radiation is going to tip them over the edge and cause life-threatening harm to them; that is a rare circumstance.

In your experience as a radiation oncologist, are patients still receiving consolidation chemotherapy after chemoradiotherapy?

At my institution, we never see that anymore. Over the past couple of years, I can’t think of any patients in whom we have used consolidation chemotherapy. We have only been giving consolidation immunotherapy.

What barriers to treatment are still faced by this population, and what is your advice on how to optimally address them?

We certainly encounter many barriers [to treatment]. Different patients experience difference psychosocial barriers, [for example]. Sometimes their support systems at home may be suboptimal, and we find that having family or friends [around] that can help with certain situations, like getting them to appointments and helping them organize information, is very helpful.

When we are assessing our patients and it seems that they lack a good support network, we will have them meet with our social work team. [These teams] can be very [in terms of] emotional support, but also with logistical support and working through some of the issues. Having social work as a presence on the oncology team can really help.

Reference

1. Spigel DR, Faivre-Finn C, Gray JE, et al. Five-year survival outcomes with durvalumab after chemoradiotherapy in unresectable stage III NSCLC: an update from the PACIFIC trial. J Clin Oncol. 2021;39(suppl 15):8511. doi:10.1200/JCO.2021.39.15_suppl.8511