Best Management Practices for a Patient With Early-Stage Non-Small Cell Lung Cancer

Aakash Desai, MD, University of Alabama, Birmingham, Alabama, discusses the course of treatment he would take for a patient with early-stage non-small cell lung cancer (NSCLC). 

Transcript: 

Hello everyone, I'm Aakash Desai, an assistant professor at the University of Alabama at Birmingham, and today I will be discussing with you a case with early-stage non-small cell lung cancer. 

As you see from the case writeup, we had a patient, a 48-year-old woman, who initially presented with hemoptysis and was found to have a lung nodule on the left upper lobe, subsequently underwent a wedge resection with pathology confirming a 1.2-centimeter tumor with lymphovascular invasion as well as clear visceral pleural and surgical margins and 1 positive lymph node at station 5, making this a pathologically stage of T1b N2M0, or stage IIIA. Post-surgery, subsequently, patient was seen by medical oncology and the discussion was to start adjuvant chemotherapy with doublet chemotherapy with carboplatin and pemetrexed, given the histology being adenocarcinoma. Subsequent testing for PD-L1 showed a PD-L1 tumor proportion score of 0% and next-generation sequencing revealed a KRAS G12C mutation. 

From the question itself, what is the next appropriate step for the management after completion of adjuvant chemotherapy, I'm going to talk a little bit about management of early-stage non-small cell lung cancer, specifically post-surgical management. 

As you know, today in stage 3 non-small cell lung cancer we have different approaches which are typically based on initially, whether this is a more resectable type of tumor, as well as whether the patients are conducive for resection from a comorbidity standpoint. Initial discussion is a multidisciplinary discussion between the thoracic surgeon, medical oncology, and radiation oncology to truly determine whether this is a surgical case or not. In general, today we have different approaches including neoadjuvant chemoimmunotherapy, perioperative immunotherapy, chemoimmunotherapy, as well as adjuvant chemotherapy followed by immunotherapy, and for the unresectable cases which are not conducive to surgical resection, we have the concurrent chemoradiation followed by immunotherapy approach. In general, the multidisciplinary discussion will be very helpful to decide what would be the right course of treatment for a patient. For this particular case, it was discussed that this patient would be a good surgical candidate, and surgery-first approach was taken. Obviously, there are alternative approaches and again, as I mentioned, depending on thoracic surgery as well as other multidisciplinary teams, the discussion would inform what the next step would be for a patient. 

Coming back to our case, the patient did undergo surgery, without any neoadjuvant chemoimmunotherapy or perioperative chemoimmunotherapy plan with the neoadjuvant component. Post-resection, an important component of decision making is whether there is a need for adjuvant chemotherapy. For patients who have had surgical resection, adjuvant chemotherapy is recommended per guidelines for patients who have tumors which are greater than 4 cm or have positive lymph node involvement. This is based on a meta-analysis, which has been now conducted in numerous studies, based on numerous studies, which have shown that there is an overall survival benefit of 5% at 5 years with adjuvant doublet chemotherapy. Based on that, this patient was treated with adjuvant carboplatin and pemetrexed chemotherapy and the next question is what do we do after that? 

Based on the data that we have for specifically patients who have underwent surgical resection followed by adjuvant chemotherapy, there are 2 studies which have shown benefit of using adjuvant immunotherapy and these are the PEARLS/KEYNOTE-091, as well as IMpower-010 studies which have shown benefit. 

The IMpower-010 study actually studied adjuvant atezolizumab in comparison to best supportive care. This was a phase 3 randomized study trying to look at the benefit of adjuvant immunotherapy in this particular population, and it demonstrated that there was an overall survival trend in favor of atezolizumab in PD-L1 ≥ 1% in stage II/IIIA population with a hazard ratio of 0.71. Specifically, when we talk about the disease-free survival (DFS), which was in this case the primary end point, there was again a benefit for the DFS in the overall analysis population and then specifically within the population with PD-L1≥ 50% the hazard ratio was 0.43. For PD-L1 1% to 49% the hazard ratio was 0.87. -Subsequently, based on this study, adjuvant atezolizumab has been approved by the FDA for a PD-L1 > 1% and that could be utilized in this particular setting with post adjuvant chemotherapy. 

The other study, which also led to the approval of adjuvant immunotherapy is adjuvant pembrolizumab approval. This was based on the PEARLS study, which showed again, pembrolizumab provided a statistically significant clinical meaningful DFS improvement compared to placebo. Again, in this randomized phase 3 study the median DFS was 53.6 months with pembrolizumab compared to 42 months with placebo with a hazard ratio of 0.76 and generally consistent DFS benefit was seen in patients across PD-L1 levels. The OS data have not been updated, and not mature yet, but there was some trend in favor of overall survival as we've seen with also the IMpower-010 and this has led to the new adjuvant treatment option with adjuvant pembrolizumab in patients with stage Ib, which tumor greater than 4 CM, to stage IIIA non-small cell lung cancer following complete resection and adjuvant chemotherapy. This is actually approved regardless of PD-L1 expression. I think there's a key caveat here where the adjuvant atezolizumab approval is for PD-L1 TPS score of more than 1%. The adjuvant pembrolizumab approval is regardless of the PD-L1 status

Based on this, we discussed with our patient for adjuvant immunotherapy, the duration of adjuvant immunotherapy here is in general for about 1 year or 12 months, and after adjuvant chemotherapy is done typically there is a discussion with the patient in terms of the risk and benefit, especially as it pertains to some immune-related adverse events, which is the risk with these adjuvant treatment options. There are some logistical challenges in the sense that this requires every 3 week or every 6 week infusions however, the benefit that we have seen in terms of disease-free survival, usually I would think provides more benefit compared to the risk and is usually my approach in discussion with our patients.