Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: The addition of bevacizumab to osimertinib does not extend progression-free survival (PFS) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) with an EGFR activating mutation, say Japanese researchers.
The WJOG9717L phase II study of patients with untreated IIIB–IV disease or recurrence after surgery was presented at the ESMO Congress 2021 by Hirotsugu Kenmotsu, from Shizuoka Cancer Center in Nagaizumi, Japan.
After a median 30.4 months, the primary endpoint of PFS by blinded independent central review did not differ significantly between the 61 patients randomly assigned to receive osimertinib 80 mg/day plus bevacizumab 15 mg/kg every 3 weeks and the 61 patients given only osimertinib, at a median 20.2 and 22.1 months, respectively.
Regarding the trial’s secondary endpoints, the objective response rate was also comparable in the combination and osimertinib-only arms, at 82% and 86%, respectively, as was overall survival, with median duration unreached in both groups. The corresponding overall survival rates were 90.2% versus 98.3% at 1 year and 81.7% versus 76.4% at 2 years.
Subgroup analysis found was no significant difference in the PFS durations of never smokers in the combination and osimertinib-only arms. There was a trend towards improved survival with the combination regimen among patients who had ever smoked, with a median PFS of 32.4 versus 13.6 months with monotherapy, but the hazard ratio (HR) of 0.481 was not significant, reported Hirotsugu Kenmotsu.
When assessed by EGFR mutation, patients with a deletion in exon 19 showed a trend towards a longer PFS with osimertinib plus bevacizumab than osimertinib alone (not reached vs 20.3 months, HR=0.622), although this did not reach statistical significance. There was also no significant difference between the treatment groups among patients with a Leu858Arg mutation in exon 21 (20.0 vs 15.7 months, HR=1.246).
Safety analysis showed that addition of bevacizumab did not shorten the duration of osimertinib treatment, at a median of 94.0 versus 57.6 weeks, but patients using the combination experienced a higher rate of grade 3–5 adverse events (AEs, 55.7 vs 48.3%) and serious AEs (32.8 vs 20.0%).
Osimertinib plus bevacizumab was also associated with a higher rate of AEs leading to treatment discontinuation (55.7 vs 26.7%) and dose modifications (63.9 vs 41.7%). There were no treatment-related deaths.
However, Hirotsugu Kenmotsu highlighted that the rate of any-grade pneumonitis in the study was markedly lower with the combination than the monotherapy, at 3.3% versus 18.3%. At grade 3, the rates were 1.6% versus 1.7%.
“This combination might reduce the risk of pneumonitis related with osimertinib”, he hypothesized.
Session discussant Natasha Leighl, from the Princess Margaret Cancer Center in Toronto, Ontario, Canada, described this “novel finding” as “extremely exciting”, raising the potential for bevacizumab being given “as a potential therapy for patients with TKI-induced ILD [interstitial lung disease] and no other options and those at very high risk of ILD, for example, perhaps, post-immunotherapy or in high-risk populations as we find in Japan.”
Natasha Leighl also commented on the finding that ever-smokers might do better with bevacizumab, saying that the finding is “largely driven by the poor outcome of patients in the osimertinib alone arm that had a smoking history.”
Nevertheless, she noted that a similar trend for smokers has also been reported in the FLAURA, WJOG8715L and ETOP 10-16 BOOSTER trials, and questioned whether there may be a “molecular basis” behind these findings.
Reference
LBA44 - Kenmotsu H, Wakuda K, Mori K, et al. Primary results of a randomized phase II study of osimertinib plus bevacizumab versus osimertinib monotherapy for untreated patients with non-squamous non-small-cell lung cancer haboring EGFR mutations; WJOG9717L study. Ann Oncol 2021;32(suppl_5):S1283–S1346. doi:10.1016/annonc/annonc741
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