FDA’s Approval of Opdivo-Chemo Regimen Spurs Another Thought-Provoking Treatment Option in Lung Cancer

In March 2022, the Food and Drug Administration (FDA) approved Opdivo (nivolumab) plus a platinum-doublet chemotherapy for patients with resectable non-small cell lung cancer (NSCLC).

It was the first immunotherapy approved to be administered to patients prior to surgery (neoadjuvant therapy), making it “hugely important,” said Upal Basu Roy, executive director of research at the LUNGevity Foundation.

“This approval definitely fills a huge unmet need in this population for sure, especially the neoadjuvant space, because this is the first drug approval in the neoadjuvant space after chemotherapy,” he explained in an interview with CURE®.

Previously, patients with diagnoses of early-stage NSCLC had different options, including either chemotherapy before (neoadjuvant) or after surgery (adjuvant).

Improvement

The approval was based on results of the phase 3 CheckMate-816 trial, which compared Opdivo plus platinum-doublet chemotherapy (179 patients) with platinum-chemotherapy alone (179 patients). Results demonstrated a significantly improved event-free survival (time after treatment ends when a patient remains free of certain complications or events) with Opdivo plus chemotherapy, at 31.6 months, compared with chemotherapy alone at 20.8 months.

“That, in my mind, is not an incremental increase; it’s a huge increase,” Basu Roy added.

Additionally, Opdivo plus chemotherapy resulted in a 37% reduction in the risk of disease progression, recurrence or death. Pathological complete response rate (no viable tumor left at the time of surgery) was 24% in the group that received Opdivo plus chemotherapy compared with 2.2% in the group that received chemotherapy alone.

Dr. Melina Elpi Marmarelis, a medical oncologist and assistant professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia called this striking.

“I would say that the snippet of results that we’ve received is good but we’re still waiting for, first of all, longer-term follow-up,” she said in an interview with CURE®. “(And) second of all, for more information about the number of patients (who) made it to surgery (and) whether there was surgical complication with this approach. The main thing we worry about in neoadjuvant clinical trials is that delaying surgery will lead to worse outcomes for patients.”

However, Basu Roy explained, this combination did not delay surgery — which is what was great about adding the immunotherapy to chemotherapy in this setting. Additionally, quality of life was similar in both groups before and after surgery, so adding immunotherapy did not affect that either.

“This particular approval is sort of a landmark approval because it’s hitting the quantity-of-life end point, which is a longer (event-free survival), but also a quality-of-life end point from a survivorship perspective because it did not add more (side effects) to a patient’s treatment,” Basu Roy explained.

Only 10% of patients receiving Opdivo plus chemotherapy experienced side effects that ultimately led to discontinuation. The most common side effects included nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%) and rash (20%) — and Basu Roy attributes most of these to the chemotherapy.

Complicating Decisions

Although this represents a significant approval for this population, Basu Roy and Marmarelis agree it may make treatment decisions more complicated.

“I think right now, this actually creates more questions than answers at this point. We have approvals for immunotherapy in the neoadjuvant and adjuvant spaces, as well as approvals for targeted therapy in the adjuvant space. We don’t yet have a good framework to think about how to combine or prioritize these. So, all of these approvals are changing our multidisciplinary workflow tremendously,” Marmarelis explained.

What that means, she added, is that patients will most likely need to start seeing a multidisciplinary team much earlier in treatment, rather than just a surgeon. Basu Roy agreed and said that with all the approvals there are different treatment options for this patient population, so patients should be treated by a multidisciplinary team including a surgeon, radiation oncologist and medical oncologist.

“I think I would be remiss in not pointing out, as a patient advocate, that in some ways this particular approval makes the treatment in early-stage lung cancer a little bit more complicated. … This care decision needs to be taken with a lot of thought and that’s why a multidisciplinary team for the treatment of early-stage lung cancer has become even more important,” Basu Roy added.

He advises patients to have open communication with their multidisciplinary care team and ask questions like why they are choosing this therapy, whether they are the right candidate for these treatment options and what the treatment decision-making process is. By asking these questions and advocating for themselves, patients can become empowered and be partners in their own care, he concluded.

Marmarelis also mentioned the importance of patients advocating for themselves, specifically in early-stage disease. She said this approval highlights the growing need for complete molecular testing at the time of biopsy. In the study that led to the approval, patients with EGFR and ALK mutations were excluded because of a known decreased efficacy of immunotherapy in this population, meaning these patients will need more personalized treatment. Patients should be advocating early for that.

“I think advocating for complete genotyping of the tumor is really important and advocating early on because the process does take several weeks often to receive those results,” she said.

Although this approval may create more uncertainty on which treatment a patient should receive, it is significant nonetheless.

“Early-stage lung cancer is still a deadly disease and any progress toward improving it is a step forward,” Marmarelis concluded.

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