1298P - Chemotherapy with concurrent proton vs. photon radiotherapy in stage III NSCLC: Effects on hematological toxicity and immune therapy

Background

Concurrent chemo-radiotherapy (CCRT) followed by adjuvant Durvalumab (D) is standard of care for fit patients (pts) with unresectable stage III NSCLC. We aimed to assess whether intensity modulated proton therapy (IMPT), compared to intensity modulated photon therapy (IMRT), can reduce hematological toxicity and whether it affects D treatment.

Methods

Retrospective data completion and analysis of a 4-center prospectively collected series of pts with stage III NSCLC receiving CCRT between 06.16-12.22, staged with FDG-PET-CT and brain imaging. Main exclusion criteria: previous cancer diagnosis and thoracic RT.

Results

271 pts were enrolled (IMPT: n=71, IMRT: n=200). All pts received platinum-based chemotherapy (CT). Median age: 66 years, 36% had a squamous NSCLC, 41% had stage IIIA NSCLC, 89% had a WHO Performance Status (PS)=0/1, 65% had PDL-1 positive and 76% received q21 CT (no differences between IMPT and IMRT). The incidence of lymphopenia grade≥3 (G≥3) was 66.7% and 47% in the IMRT and IMPT arm respectively (p=0.032, OR 2.2, 95% CI: 1.03-4.9). In a multivariable logistic model including WHO PS, type and schedule of CT, age and gross tumor volume, IMRT remained significantly associated with higher risk of lymphopenia G≥3 (adjusted OR=2.6, 95% CI: 1.1-6.2, p=0.029). The incidence of anemia G≥3 during CCRT in the IMRT and IMPT arm was 26% and 8.5% respectively (adjusted OR=4.9, 95% CI: 1.9-12.6, p=0.001). Spearman's correlation coefficient between anemia G≥3 and body mean dose (BMD) was 0.052 (p=0.001). IMPT significantly reduced BMD compared to IMRT (p=0.04). IMPT was associated with a lower rate of PS≥2 at day 21 and 42 after CCRT (13.4% vs. 26%, p=0.039, OR 0.44 and 24% vs. 39%, p=0.024, OR 0.49, respectively). Pts treated with IMPT had higher probability of receiving adjuvant D (74% vs 52%, adjusted OR 0.35, 95% CI: 0.16-0.79, p=0.012). In the multivariable logistic model (including age and PS) IMPT was the only predictive factor for receiving D within 42 days (72% vs 51%, adjusted OR 0.4, 95% CI: 0.16-0.95, p=0.04).

Conclusions

IMPT can reduce severe lymphopenia and anemia in pts with unresectable stage III NSCLC. Pts treated with IMPT have a better PS after CCRT and they are more likely to receive adjuvant durvalumab.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L. Hendriks: Financial Interests, Institutional, Advisory Board: Amgen, Boehringer Ingelheim, Lilly, Novartis, Pfizer, Takeda, BMS, Merck, Janssen, MSD; Financial Interests, Personal, Other, mentorship with key opinion leaders funded by AstraZeneca: AstraZeneca; Financial Interests, Institutional, Invited Speaker, for educational webinar: AstraZeneca, Lilly; Financial Interests, Institutional, Invited Speaker, educational webinar/interview: Bayer; Financial Interests, Institutional, Invited Speaker, educationals: MSD; Financial Interests, Personal, Invited Speaker, for webinars: Medtalks; Financial Interests, Institutional, Advisory Board, one time also personal: Roche; Financial Interests, Institutional, Other, performing interviews at conference: Roche; Financial Interests, Personal, Other, travel support: Roche; Financial Interests, Institutional, Other, podcast on brain metastases: Takeda; Financial Interests, Personal, Invited Speaker, payment for post ASCO round table discussion: VJOncology; Financial Interests, Personal, Invited Speaker, payment for post ASCO/ESMO/WCLC presentations, educational committee member: Benecke; Financial Interests, Institutional, Invited Speaker, payment for post ESMO/ASCO discussion: high5oncology; Financial Interests, Institutional, Other, educational webinar: Janssen; 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, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, GSK, Novartis, Merck Serono, Roche, Takeda, Blueprint Medicines, Mirati, AbbVie, MSD, Gilead; Non-Financial Interests, Other, secretary NVALT studies foundation: NVALT; Financial Interests, Institutional, Research Grant, donation for health care improvement project: Merck; Financial Interests, Institutional, Research Grant, funding for healthcare improvement project: Pfizer; Non-Financial Interests, Other, Chair metastatic NSCLC for lung cancer group: EORTC. D. De Ruysscher: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Philips Health, AstraZeneca; Financial Interests, Institutional, Coordinating PI: BMS, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Varian; Financial Interests, Funding: Olink; Financial Interests, Institutional, Funding: BeiGene; Financial Interests, Institutional, Other, Advise group brain metastases NSCLC: Eli Lilly. All other authors have declared no conflicts of interest.