Refining Treatment Timelines and Immunotherapy Strategies in Early-Stage NSCLC: Jonathan Thompson, MD, MS

At a recent Institute for Value-Based Medicine® event, Jonathan Thompson, MD, MS, a hematology, medical oncology specialist and associate professor at Froedtert and the Medical College of Wisconsin in Milwaukee, emphasized that delays between biopsy and treatment initiation in non–small cell lung cancer—often lasting several weeks—can negatively impact outcomes, particularly in early-stage disease. He noted that access barriers to specialists and the lack of reflex biomarker testing are key contributors, underscoring the importance of having results available at the time of oncology consultation to avoid further delays.

Regarding immunotherapy in the perioperative setting, Thompson highlighted ongoing uncertainty about optimal strategies and duration. Drawing on data from trials such as CheckMate 816 (NCT02998528), he explained that patients who achieve a complete pathologic response to neoadjuvant chemo-immunotherapy often experience excellent long-term survival without additional therapy, suggesting that extended immunotherapy in this subgroup may not add benefit and could expose patients to unnecessary toxicity.

This is the third part of a 6-part interview series with Thompson.

This transcript was lightly edited; captions were auto-generated.

Transcript

How does time from initial presentation to treatment initiation impact outcomes, and what are the key challenges contributing to delays in molecular testing and treatment selection?

Time to treatment is a real challenge in our field. Commonly, from the time a patient has a biopsy to the time they're actually starting their cancer treatment, whether systemic therapy, radiation therapy, or surgery—commonly, we're facing weeks in between those time periods. The barriers that exist largely depend on access to health care providers, like medical oncologists, radiation oncologists, and surgeons. But beyond that, delays in biomarker testing can drive some of these treatment delays that, if we're only doing the biomarker testing after they've met the medical oncologist, we've probably lost a number of weeks of time, and that really is the argument for trying to do most of our biomarker testing as reflex, so that we have the information in hand at the time of the visit with the medical oncologist so we're not waiting additional weeks for that. We do know, especially for early-stage patients, that the longer we wait before they start their neoadjuvant therapy or before they have their surgery, the less favorable survival outcomes that they have.

Immunotherapy continues to evolve across the lung cancer spectrum, now extending into perioperative use. What are the key considerations for determining optimal duration of therapy?

Photomicrograph of fine needle aspiration cytology of a lung nodule showing non–small cell lung cancer. Image Credit: © Saiful52 - stock.adobe.com

We have a wealth of options nowadays in terms of using immunotherapy for early-stage patients; that includes using a neoadjuvant chemo-immunotherapy alone, that includes using neoadjuvant chemo-immunotherapy followed by surgery followed by adjuvant immunotherapy, or it includes surgery followed by adjuvant chemo-immunotherapy. Some of the challenges right now are we don't know exactly which strategy is optimal and whether there is truly one right strategy for each patient. Hopefully some of those questions will be answered in clinical trials.

In terms of duration of immunotherapy, I think we have pretty strong signals from readouts of clinical trials like CheckMate 816. In that trial, patients with early-stage Ib to III non–small cell lung cancer received 3 cycles of chemotherapy with nivolumab (Opdivo; Bristol Myers Squibb), the PD1 inhibitor, and then went on to surgery, and then most patients tend to receive adjuvant therapy from there. What that study showed is that those patients who had the best overall response to the chemo-immunotherapy, those who had a complete pathologic response, meaning no viable tumor left over in the surgical sample, those patients did extremely well, so very few patients had cancer recurrence after surgery, to the tune that at about 5 years out from starting participation in the trial, that about 95% of those patients were still alive, who had that complete pathologic response. For those patients, at least in my practice, if you have a [pathologic complete response], I tend to not have additional immunotherapy, just because there doesn't seem to be much benefit from that. On the other hand, adding a year of immunotherapy for those patients, besides not adding benefit, you do expose them to potential risk from toxicity from the checkpoint inhibitor. For that patient population, I think we can, at least in my mind, safely de-escalate their duration of therapy and still have excellent outcomes.