Early stage non small cell lung cancer

 

SBRT versus systemic therapy for early-stage inoperable nonsmall cell

1. SABR is well tolerated. Slightly more toxic for tumors within 2 cm of the central airways. Hemoptysis can be the result.

2. A 5-year pattern of failure:  5-year in-field, locoregional, and distant failure rates of 7.3%, 25.5%, and 23.6%, respectively, and 5-year DFS of 25.5%. However one trial showed path CR of only 60% when the tumor was resected after SBRT.

Reference: JCO Jan 2022

5-year OS rates of 68% in stage IB, 53%-60% in stage II, and 36% in stage IIIA 

Early stage lung cancer Adjuvant chemo

benefit of chemo --> improved OS by 4% at 5 yr in tumors that are node positive or > 4 cm.

1. International Adjuvant Lung Cancer Trial :resected stage I-III NSCLC to three to four cycles of cisplatin-based adjuvant chemotherapy versus observation. At 5 years, chemotherapy improved OS from 40.4% to 44.5%

2. JBR.10 trial, which enrolled stage IB-II resected NSCLC and demonstrated an improvement in 5-year OS from 54% to 69% with four cycles vinorelbine/cisplatin as compared to observation

3. ANITA: cisplatin/vinorelbine improved 5-year OS by 8.6% in resected stage IB or IIIA NSCLC

Current National Comprehensive Cancer Network (NCCN) guidelines for NSCLC include a recommendation to consider chemotherapy for high-risk node-negative patients, for features including size > 4 cm, visceral pleural involvement, poorly differentiated tumors, vascular invasion, although resected via wedge resection, and unknown nodal involvement

Early stage lung ca: Adjuvant TKI

1. EGFR mutated stage I to III:

ADAURA randomly assigned patients with resected stage IB-IIIA NSCLC with an EGFR exon 19 deletion or L858R mutation to adjuvant osimertinib or placebo for up to 3 years. Adjuvant chemotherapy before osimertinib was allowed but not mandated. DFS improvement found with osimertinib, with 2-year DFS of 90% with osimertinib and 44% with placebo HR, 0.17.

ADAURA findings could potentially be extrapolated to the medically inoperable population of patients with EGFR mutations 

2. ALCHEMIST trial is testing adjuvant ALK mutated lung ca adjuvant rx.

Early stage lung ca: Adjuvant immunotherapy

1. Atezolizumab

IMPower 010: ICI following 4 cycles adjuvant chemo in stage II-IIIA post resection: IM power 010--> greatest DFS benefit HR 0.4 in those with PDL1 50 or higher. Give atezo for 1 yr. Approved for PDL1> 1% but DFS benefit not so impressive. 

2. Pembrolizumab: Keynote 091- showed DFS benefit irrespective of PDL1. 18 cycles q 3 weeks. OS data, not mature

ADAURA, Keynote091, and IMpower 010 all showed a DFS rather than OS benefit.

Consolidation ICI after 2 cycles CRT for stage III non small cell

1. PACIFIC trial- PD-L1 inhibitor durvalumab

phase III, placebo-controlled PACIFIC trial of patients with unresectable, stage III non–small-cell lung cancer (NSCLC) whose disease had not progressed after platinum-based concurrent chemoradiotherapy (CRT), administration of durvalumab (a programmed cell death-ligand 1 [PD-L1] inhibitor) for up to 12 months improved overall survival (OS; stratified hazard ratio [HR], 0.68. OS and PFS : 42.9% remain alive at 5 years and 33.1% remain alive and progression-free

Median OS was 47.5 months with durvalumab versus 29.1 months with placebo. The estimated 5-year OS rate was 42.9% with durvalumab versus 33.4% with placebo.

No OS benefit if PDL1 =0 , however there was a PFS  benefit in this group also.

PACIFIC trial in stage III NSCLC found that patients who were randomly assigned within 14 days of completing radiotherapy experienced greater benefit from durvalumab (HR 0.39 for PFS) than those with ≥ 14 days between radiation and ICI

Reference: JCO : https://ascopubs-org.offcampus.lib.washington.edu/doi/full/10.1200/JCO.22.00873