Abstract 957P
Background
Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab (D) represents standard of care for fit patients (pts) with unresectable stage III NSCLC. Aim: assess whether intensity modulated proton therapy (IMPT), compared to intensity modulated photon therapy (IMRT) can reduce lymphopenia (primary endpoint), and other toxicities; and whether IMPT affects immune related adverse events (irAEs) incidence.
Methods
Retrospective data completion and analysis of a four-center prospectively collected series of pts with stage III NSCLC receiving CCRT between 06.16-02.22, staged with FDG-PET-CT and brain imaging.
Results
228 patients were enrolled (IMPT: n=46, IMRT: n=182) from 355 identified patients. Main reasons for exclusion were previous cancer, previous thoracic RT. All pts received 60-66Gy of RT and platinum based chemotherapy (CT). Median age 66 years, 58% male, 33% squamous histology, 42% stage IIIA, 91% WHO Performance Status (PS)=0/1, 63% PDL-1 positive tumor and 75% received 3-weekly (Q3W) CT (No significant differences between IMPT and IMRT). Lymphopenia grade(G)≥3 incidence during CCRT was not statistically different between IMPT and IMRT (57% vs 65%, p=0.3). IMRT treated pts, had higher risk of anemia grade(G)≥3 (p=0.049, OR=2.2, 95% CI:0.94-5.2). Persistent toxicities G≥2 at day 42 after CCRT were higher with IMRT: cough (p=0.001, OR=3.3, 95% CI:1.3-7.8), esophagitis (p<0.001, OR=2.8, 95% CI:1.4-5.7), dyspnea (p=0.001, OR=3.4, 95% CI:1.4-8), anorexia (p<0.001, OR=3.2, 95% CI:1.4-7.7). Among pts treated with Q3W CT, IMPT reduced lymphopenia G≥3 rate (p=0.049, OR=0.4, 95% CI:0.2-0.9), and IMPT was associated with a lower rate of PS≥2 at day 21 after CCRT (15% vs. 30%, p=0.041, OR:0.8, 95% CI 0.68-0.96). All the above mentioned findings remained significant at multivariate analyses. Among pts treated with D (n=105), incidence of irAEs (p=0.3) and pneumonitis (p=0.55) were similar between IMPT and IMRT.
Conclusions
IMPT reduced CCRT persistent toxicities 42 days post-RT, potentially increasing the number of pts eligible for adjuvant D. IMPT toxicity profile was better especially in pts treated with Q3W CT. The lower RT dose delivered organs at risk with IMPT might explain our findings.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
L. Hendriks: Financial Interests, Institutional, Advisory Board: BMS, Boehringer Ingelheim, Lilly, Takeda, Amgen, Pfizer; Financial Interests, Institutional, Advisory Board, one time also personal: Roche; Financial Interests, Institutional, Other, performing interviews at conference: Roche; Financial Interests, Personal, Other, mentorship with key opinion leaders funded by AstraZeneca: AstraZeneca; Financial Interests, Personal, Invited Speaker, for webinars: Medtalks; Financial Interests, Institutional, Invited Speaker: MSD, AstraZeneca, GSK, Novartis, Merck Serono, Roche, Takeda, Blueprint Medicines, Mirati, Janssen; Financial Interests, Personal, Other, travel support: Roche, BMS; Financial Interests, Personal, Invited Speaker, payment for post ASCO round table discussion: VJOncology; Financial Interests, Institutional, Invited Speaker, payment for post ESMO discussion: high5oncology; Financial Interests, Personal, Invited Speaker, payment for post ASCO/ESMO/WCLC presentations, Educational Committee Member: Benecke; Financial Interests, Personal, Other, Member of the committee that revised these guidelines: Dutch guidelines NSCLC, brain metastases and leptomeningeal metastases; Financial Interests, Institutional, Research Grant, for IIS: Roche, Boehringer Ingelheim, AstraZeneca; Financial Interests, Institutional, Research Grant, for IIS (contract in negotiation): Takeda; Financial Interests, Institutional, Other, drug support for IIS (contract in negotiation): BeiGene; Non-Financial Interests, Other, Chair metastatic NSCLC for lung cancer group: EORTC; Non-Financial Interests, Other, secretary NVALT studies foundation: NVALT. D. De Ruysscher: Financial Interests, Institutional, Invited Speaker: Philips Health, BMS, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Varian; Financial Interests, Funding: Olink; Financial Interests, Institutional, Funding: BeiGene. All other authors have declared no conflicts of interest.