Piotr Wysocki: Osimertinib after radiochemotherapy improves PFS in EGFR-mutated NSCLC patients – but is it really what they need?

Piotr Wysocki recently posted on LinkedIn:

“The results of the LAURA study were presented during a plenary session at the ASCO 2024 Annual Meeting and simultaneously published in the New England Journal of Medicine. This phase III study evaluated the role of osimertinib in stage III EGFR-mut (exon 19 deletion or exon 21 codon p.Leu858Arg) NSCLC patients who underwent chemoradiotherapy. Within 6 weeks after completion of chemoradiotherapy, 216 with disease control were randomized (2:1) to osimertinib or placebo administered until disease progression or unacceptable toxicity. The primary endpoint was PFS.

After a median follow-up of 22.0 months for osimertinib and 5.6 months for placebo, the median PFS was 39.1 months (osimertinib) and 5.6 months (placebo), which translated into an HR for PFS = 0.16 (95% CI, 0.10 to 0.24). The percentages of patients who were alive and progression-free at 12 months and 24 months, were 74 and 65% with osimertinib and 22% and 13%  with placebo, respectively.

The data maturity for overall survival was 20% (43 patients had died). The 36-month OS was 84% with osimertinib and 74% with placebo, strongly suggesting that significant improvement in PFS will probably not translate into similar benefit in long-term outcomes. It is worth noting that 79% in the placebo arm received third-generation EGFR-TKI upon progression.

Treatment-emergent adverse events, which even at low grade can negatively impact a patient’s quality of life, occurred much more often in the osimertinib arm than placebo (diarrhea G1-3 – 36% v. 14%; rash G1-2 24% v. 14%; paronychia G1-2 17% v. 1%; decreased appetite G1-3 – 15% v. 5%; stomatitis G1-2 12% v. 3%). The authors have provided no quality-of-life data.

The LAURA study demonstrates that osimertinib administered immediately (within 6 weeks) after chemoradiotherapy postpones progression but probably does not improve long-term outcomes and thus has no curative potential.

So, once osimertinib is approved in this setting, the options for EGFR-mutated NSCLC patients after aggressive and exhausting non-curative radiochemotherapy will be as follows:

1.        Immediate start of osimertinib, which will delay progression at the cost of increased toxicity and presumably impaired quality of life

2.        Active observation, time for convalescence, treatment-free interval (months or even years), maintenance of quality of life, no negative impact on long-term outcomes.

I have no doubts about what I will advise my patients.”

Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC

Authors: Shun Lu, Terufumi Kato, Xiaorong Dong, Myung-Ju Ahn, Le-Van Quang, Nopadol Soparattanapaisarn, Takako Inoue, Chih-Liang Wang, Meijuan Huang, James Chih-Hsin Yang, Manuel Cobo, Mustafa Özgüroğlu, Ignacio Casarini, Dang-Van Khiem, Virote Sriuranpong, Eduardo Cronemberger, Toshiaki Takahashi, Yotsawaj Runglodvatana, Ming Chen, Xiangning Huang, Ellie Grainger, Dana Ghiorghiu, Toon van der Gronde and Suresh S. Ramalingam.