Unmet Needs and Future Directions in Non–Small Cell Lung Cancer


Sandip P. Patel, MD, offers advice to fellow oncologists and highlights unmet needs and future directions in the treatment of patients with non–small cell lung cancer.

Case: A 60-Year-Old Woman with Early-Stage Non–Small Cell Lung Cancer

Initial presentation and Clinical Workup

  • Healthy 60-year-old Caucasian woman, 45 pack-year smoker, presented with a nonproductive cough
    • Physical exam revealed ECOG PS 0, BP: 120/93, HR: 74 bpm, BMI: 22
    • Pulm: lungs CTA bilaterally
    • Chest X-Ray: 5.5-cm right mass in right upper lobe
    • CT chest/abdomen: lobulated 5.5 x 5.1-cm mass in right upper lobe
    • Biopsy of Right Upper Lobe: adenocarcinoma, TTF1 (+) consistent with NSCLC
    • Labs are WNL; PET Imaging: negative for any lymph nodes or distant metastasis; Brain MRI: negative; PFTs: Normal


  • Mediastinoscopy with negative lymph nodes on frozen section, followed by right upper lobectomy without complications
  • Current ECOG PS remains 0
  • Histopathology reveals 5.5-cm tumor with negative margins; 0 nodes positive for malignancy (2R, 4R, 7, and 11R are all negative)
  • Patient is diagnosed with stage IIA (pT3N0M0) lung adenocarcinoma
  • Molecular testing shows EGFR exon (19del) and PD-L1 expression of 40%.
  • Post operation, the patient completes 4 cycles of adjuvant chemotherapy with cisplatin + pemetrexed. Her ECOG PS is 1.
  • Patient begins treatment with osimertinib. 20 months after initiating osimertinib, the patient reports headaches and worsening fatigue.
  • CT scans revealed 3 new liver lesions and Brain MRI visualized 1 new lesion.

This is a video synopsis/summary of a Case-Based Peer Perspectives featuring Sandip P. Patel, MD.

Major unmet needs in non–small cell lung cancer (NSCLC) include discovering targetable mutations among the nearly one-third of patients without currently actionable alterations and overcoming inevitable acquired resistance to available targeted therapies like EGFR, ALK, and ROS1 inhibitors. Understanding resistance mechanisms molecularly will facilitate development of rational next-line targeted options and combinations to overcome bypass signaling pathways.

The key takeaway is that comprehensive molecular profiling, whether via tissue or circulating tumor DNA, provides a road map to align patients with the most appropriate treatment for their cancer’s genomic profile. Though testing has upfront costs, improper treatment without the insight testing provides is associated with significantly greater expenses from excessive toxicity and limited efficacy. Molecularly guided therapy selection maximizes clinical benefit and quality of life while minimizing ineffective cytotoxic therapy. Ongoing advances will uncover new targetable vulnerabilities to exploit therapeutically.

Video synopsis is AI-generated and reviewed by Targeted Oncology™ editorial staff.

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