Bristol-Myers Squibb gave oncologists a look at the results of its trial of first-line Opdivo in non-small cell lung cancer (NSCLC), and the data were as bad as feared.
The PD-1 inhibitor actually performed worse than chemotherapy in the CheckMate-026 trial, extending progression-free survival (PFS) by 4.2 months compared to 5.9 months in the comparator arm, which was described by Sanford Bernstein analyst Tim Anderson as a "worst-case scenario".
Overall survival came in at 14.4 months and 13.2 months respectively, which was not a statistically significant difference, and even a look at different patient subgroups separated by levels of PD-L1 expression yielded no comfort for BMS.
There was no evidence of a beneficial effect for Opdivo (nivolumab) regardless of PD-L1 expression level. Meanwhile rival PD-1 inhibitor Keytruda (pembrolizumab) from Merck & Co showed it could outperform chemo in NSCLC patients with 50% or greater PD-L1 expression levels. In that trial, the median PFS for Keytruda was 10.3 months, compared to six months for chemotherapy.
Both studies presented reported at the European Society of Medical Oncology (ESMO) conference in Copenhagen.
Even though BMS gave advance warning of the disappointing data in August, the unveiling of the actual figures spurred a sell-off in BMS' shares as the realisation dawned that Opdivo (nivolumab) has ceded control of the first-line NSCLC category to Keytruda - at least for now. Keytruda is under regulatory review for untreated NSCLC and an FDA decision is due by 24 December.
The CheckMate-026 results "strengthen our belief that the majority of previously untreated NSCLC patients may require combination therapy in order to experience an improved benefit versus chemotherapy," commented Fouad Namouni, BMS' head of cancer drug development.
The company is hopeful that the combination of Opdivo with CTLA4 inhibitor Yervoy (ipilimumab) in PD-L1-positive NSCLC, and alongside chemotherapy in low-expressers, will give the drug a role to play in first-line NSCLC therapy.
That is a big deal for the future success of the two drugs as NSCLC is so common, although Opdivo is still expected to grow strongly thanks to its use in other approved indications such as melanoma, previously-treated NSCLC and second-line renal cancer, as well as new uses.
At ESMO, BMS also reported encouraging results for Opdivo in previously-treated patients with bladder cancer as well as providing a detailed look at the results of the phase III CheckMate-141 trial in advanced head and neck cancer, which has already formed the basis of regulatory filings.
The company also presented preliminary results from a trial of two doses of Opdivo in neoadjuvant (pre-surgery) lung cancer, suggesting use of the drug is "safe and feasible" in this setting. All told, 40% of patients in the study showed a "major pathological regression" on tumour biopsies. Whether that has any clinical impact remains to be seen in further studies.