Bristol Myers joins AstraZeneca, Merck in touting positive lung cancer drug use around surgery

It’s not a proper market showdown without all the players. And in the perioperative treatment of early-stage, non-small cell lung cancer with a PD-1/L1 inhibitor, the field is quickly taking shape.

Compared with using chemotherapy alone before surgery, adding Bristol Myers Squibb’s Opdivo—both before and after surgery—significantly reduced the risk of tumor recurrence, progression or death in patients with early-stage NSCLC, the company said Friday. The patients had resectable cancers ranging from stages 2 to 3b.

The positive readout from the phase 3 CheckMate-77T trial puts Bristol on a collision course with fellow anti-PD-1/L1 drug developers AstraZeneca and Merck & Co., which have recently trumpeted their own data in this perioperative NSCLC setting.

All the datasets in early-stage NSCLC have prompted doctors to voice concerns about a “messy” situation, where treatment choices are difficult to make. Besides which agent to pick, a key debate focuses on whether a PD-1/L1 inhibitor is necessary both before and after surgery, or if just one treatment period is enough.

While no trial so far can directly answer that question, CheckMate-77T may offer some clarity.

Before CheckMate-77T, Opdivo last year already won the FDA’s approval as a neoadjuvant therapy used before surgery based on data from the CheckMate-816 trial. There, Opdivo’s addition to chemo reduced the risk of disease recurrence, progression or death by 37%.

With CheckMate-77T, BMS tested Opdivo after surgery as well in the adjuvant setting. So, if the magnitude of improvement in event-free survival is larger than in CheckMate-816, it may suggest that adjuvant treatment is beneficial on top of neoadjuvant therapy.

Still, that cross-trial comparison should be made with caution. For one thing, CheckMate-816 randomized patients with stage 1b to 3a disease, whereas the 77T study enrolled in stages 2 to 3b.

CheckMate-77T will also give industry watchers a chance to compare Opdivo with Merck’s Keytruda and AstraZeneca’s Imfinzi in the same perioperative setting.

Previously, Keytruda showed a 42% event-free survival benefit in the Keynote-671 trial, and Imfinzi pulled off a 32% improvement in the AEGEAN trial after a shorter follow-up time. All three studies enrolled stage 2 to 3b patients.

Like the other two competitor trials, CheckMate-77T remains ongoing to assess whether the Opdivo regimen can extend patients’ lives. At an interim analysis of Keynote-671, perioperative Keytruda cut the risk of death by 27%, which hasn’t met statistical significance.

In a three-year follow-up of CheckMate-618, neoadjuvant Opdivo showed an overall survival improvement of 38%, which also remained immature at the time of analysis.

Meanwhile, Roche is looking to join the perioperative NSCLC game with Tecentriq. The PD-L1 inhibitor got the class’s first adjuvant NSCLC nod in 2021, only to be outshone by Keytruda with a broader label this January.

Roche is testing Tecentriq in a similar neoadjuvant-plus-adjuvant setting in the Impower-030 trial, with a delayed readout now expected in 2024.