A Surgeon’s Perspective: How to Optimize Outcomes With Neoadjuvant Chemo/IO in Lung Cancer

The potential of induction chemoimmunotherapy to elicit responses in previously inoperable patients with lung cancer, thus making operation a possibility, has been raised as surgery’s role evolves, according to Eric Vallieres, MD, FRCSC. Vallieres added that despite this new treatment outlook, challenges continue to persist regarding resectability and optimizing treatment.

“There is no doubt in my mind that if we can achieve [an optimal role for induction chemoimmunotherapy], the role of surgery for [eligible] patients is going to go up. However, we cannot leave cancer behind [following operation]. If we leave cancer behind, it’s the wrong treatment,” Vallieres explained in an interview following an OncLive®State of the Science Summit™, which he co-chaired.

In the interview, Vallieres, who is a surgical oncologist and serves as the medical director of the Division of Thoracic Surgery at the Swedish Medical Center in Seattle, Washington, discussed the evolving role of surgery in lung cancer treatment following the implementation of new neoadjuvant and adjuvant treatments. He also highlighted the potential benefit of induction chemoimmunotherapy prior to surgery and expanded on the importance of assessing resectability and the strategic use of preoperative treatments to improve patient outcomes.

OncLive: How has the role of surgery evolved with the implementation of additional neoadjuvant and adjuvant treatment options?

Vallieres: We don’t have all the answers; however, as a result of giving patients induction chemoimmunotherapy, we will be able to offer surgery to a group of patients who historically were not deemed surgical candidates and would have been placed on the phase 3 PACIFIC trial [NCT02125461] regimen [or a similar regimen]. The rationale is [because] we’re seeing response rates that we had never seen before with cytotoxic [agents] alone. For local control surgery is the best strategy, and looking at the PACIFIC data, the only thing that changed was the addition of a checkpoint inhibitor on the back end—it is not that the radiation [administered] changed. If we do the same [therapy] and add a checkpoint inhibitor to the best local treatment that there is, this will lead to surgery being offered to more patients in the future.

The failure of surgery for these patients historically [occurred] more commonly outside of the surgical box [as it was due to] systemic [therapy]. If we have better systemic treatment, it makes sense that we’re going to be asked to do a better job in controlling the [disease], and surgery is a better option for that. Overall, it remains to be seen [if] we will have a study [for] individuals who are at the high end of where we would consider surgery an option [to evaluate] preoperative chemoimmunotherapy, surgery, and maybe post-operative immunotherapy vs the PACIFIC regimen? I don’t know if we’ll ever get there, though it would be ideal.

How do you define resectability and what factors are you looking for when trying to identify who may be a candidate to go to surgery?

Regarding resectability, particularly with advanced disease, you have to be as certain as you can that you’re going to remove all disease. If you know ahead of time that you’re going to be leaving disease behind, you have no business [operating]. The big question [is] if it is possible [for] patients where—[based on] imaging at diagnosis—you know that you’d be leaving disease behind [following operation]. [If you] give induction chemoimmunotherapy [to these patients, can you] bring [them] to a stage of cancer where you’re not going to leave disease behind? That’s the big unknown question.

However, it’s not always easy [to determine optimal timing for treatments], and a lot of that comes with experience. A lot of it comes with how aggressive individuals are in a particular center and how much experience they have in making those decisions. It’s possible that we’re going to learn more in that window about what we can and can’t do with induction chemoimmunotherapy. Overall, if we know we’re going to leave disease behind, there is no business doing surgery—that’s true for T disease or N disease.

How do you weigh the benefits vs toxicity concerns with perioperative treatment?

There are patients in the trials that we’ve seen so far who don’t make it to surgery. This is where, up-front, you have [treatments that don’t work for these patients]. However, if a patient [has disease that is] borderline to start with physiologically, unless there’s something you can improve upon [such as] quitting smoking, they’re not going to be in a better shape physiologically after induction chemoimmunotherapy. For those patients, you have to make a decision up-front [regarding course of treatment].

If patients who are surgical [candidates] are going to need adjuvant treatment because they already have N1 or N2 disease or their tumor is large and evolving [at a size of] 40 mm, those are individuals I would like to give [therapy] to in the preoperative setting. This is because I believe there are theoretical advantages in exposing patients to these agents before you take out the lymph nodes in the cancer.

Although we have data to support the use of these agents in the adjuvant setting, the response rates are significantly higher if you give them to patients before surgery. If someone has a small cancer and their risk of needing any form of adjuvant therapy is very low, I’m not going to give them induction therapy; instead, I’m going to go straight to surgery.

Another group of patients who are uncommon are those who will need more than a lobectomy, [where] they need a bilobectomy—[they have] resectable [disease and] don’t have any nodal disease—but they’re going to need a bigger operation. I will try to give those patients induction chemoimmunotherapy if possible to give them less of an operation afterward. That’s not fully known territory yet, but this is [something] I would like to give to these patients.