Treatment Sequencing Algorithms and Clinical Approaches

The panel presents individual sequencing strategies for EGFR-mutant advanced NSCLC. Dr. Camidge favors modified FLAURA-2 approaches, starting osimertinib monotherapy to establish patient relationships and toxicity tolerance before adding platinum-pemetrexed within 6 weeks unless contraindicated. Approximately 20% of his generally fit Denver population receives osimertinib monotherapy.

Upon progression, Dr. Camidge considers consolidation radiation before dropping chemotherapy, creating extended cytotoxic-free intervals that support platinum rechallenge at subsequent progression.

Dr. Rotow similarly defaults to FLAURA-2 in her Northwest population typically eligible for chemotherapy combinations. At progression, she assesses platinum rechallenge appropriateness based on progression characteristics, choosing between COMPEL and MARIPOSA-2 accordingly. Datopotamab deruxtecan follows, with amivantamab integration if not previously used.

Dr. Devarakonda agrees that osimertinib monotherapy remains appropriate for selected patients without clear intensification needs, though representing a minority. He favors FLAURA-2 as default, adding chemotherapy after initial targeted therapy establishment. Post-progression strategies depend on chemotherapy intervals and progression patterns, maintaining TKI continuation when possible.

Dr. Lopes acknowledges uncertainty identifying optimal monotherapy candidates, defaulting to FLAURA-2 approaches with treatment to maximum response followed by consolidative radiation for incomplete responders. Second-line approaches include COMPEL for prior monotherapy patients or amivantamab-chemotherapy combinations, with some patients preferring datopotamab deruxtecan based on response rate data.

Clinical trial participation remains important throughout treatment sequences, particularly given the 4-year survival plateau highlighting the need for curative approaches rather than prolonged disease control.