Options for Systemic Therapy in Locally Advanced NSCLC

Jyoti Patel, MD:Our patient who had borderline pulmonary function and multistationed stage 3A disease has a couple of options for therapy. Because he’s not a candidate for resection, he’d be treated with concurrent chemoradiation, which is feasible. Certainly, we have data over decades that show that concurrent therapy is better than sequential therapy, and sequential therapy, by and large, we save for patients in whom toxicity would be a significant issue.

So, for this gentleman, there are multiple regimens in which we could treat him. Because he has adenocarcinoma histology, reasonable regimens would include everything from weekly carboplatin/paclitaxel to cisplatin/etoposide or just cisplatin/pemetrexed. There’s no 1 clear winner. These regimens are often defined by what expected toxicities we would imagine. So, in a patient with preexisting neuropathy or renal dysfunction, likely we would do weekly carboplatin/paclitaxel. For a patient who had good renal function, likely we would do cisplatin/etoposide or cisplatin/pemetrexed.

For this gentleman, I chose cisplatin/etoposide primarily because that is a regimen with which I have significant comfort. The chemotherapy fits completely during the duration of radiation, and so it’s discrete over those 6 weeks. And because the toxicity tends to be minimal—maybe some alopecia and some myelosuppression—generally, it’s quite well tolerated.

So, certainly our treatment of stage 3 disease has evolved over time, as now we’ve gotten closer to an appropriate radiation dose where, normally, patients in the United States are treated between 60 and 66 gray. What has not been as clear in recent years is what the appropriate chemotherapy backbone is for these patients. A widely adopted standard based on phase II data and then replicated in the RTOG trial demonstrated that you could give concurrent carboplatin/paclitaxel with radiation followed by consolidation carboplatin and paclitaxel. And that led to a very favorable outcome in the RTOG study.

However, it’s not clear how much that consolidation does, although that has been widely adopted in the United States. Many people though, because of the difficulty of getting consolidation in after chemoradiation, choose to give cisplatin/etoposide. And during that, patients are getting a substantive dose of cisplatin—day 1 and day 8 and then again for the second part of the radiation. And so, generally, my feeling is that patients who have that initial chemotherapy regimen with cisplatin/etoposide can or have completed therapy. We know that consolidation docetaxel leads to inferior outcomes, as demonstrated by the Hoosier Oncology Network.

Cisplatin/pemetrexed has been tested in the PROCLAIM trial, and patients got consolidation pemetrexed. Again, we don’t have a comparator without pemetrexed, so, often, we just give the 3 cycles of cisplatin and pemetrexed and call it a day.

Transcript edited for clarity.

• A 63-year-old man presented to his PCP with intermittent cough and difficulty breathing on exertion
• PMH: hyperlipidemia well-managed on simvastatin; hypothyroidism, managed on levothyroxine, COPD on inhalers
• Recently quit smoking; has a 40-pack-year history
• PE; intermittent wheezing; ECOG 1
• Creatinine clearance, WNL
• Imaging Studies:
  • Chest X-ray showed opacity in the lung right upper lobe
  • Chest CT revealed a 3.1-cm spiculated mass in the right upper lobe and 2 enlarged right mediastinal lymph nodes measuring 1.5 cm and 1.7 cm; moderate emphysema noted
  • PET confirmed the lung lesion and mediastinal lymphadenopathy without evidence of distant metastasis
  • Brain MRI was negative
• Bronchoscopy with transbronchial lung biopsy and lymph node sampling revealed adenocarcinoma with positive nodes in stations 4R and 7; level 4L was negative
• Genetic testing was negative for known driver mutations
• Staging: T2aN2M0, stage IIIA
• Based on the extent of mediastinal disease and emphysema, the patient’s cancer was deemed inoperable, and he was referred for consideration of concurrent chemotherapy and radiation
• He underwent therapy with cisplatin/etoposide and concurrent thoracic radiotherapy
• Follow-up imaging showed a partial response with shrinkage of the primary and nodal lesions