This Month's Articles
Lung Cancer
Title: Perioperative Nivolumab and Chemotherapy in Stage III Non–Small-Cell Lung Cancer
Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2215530
Rating: 8. This provides significant rationale for the utilization of immune checkpoint inhibitors (ICI) in the neo-adjuvant setting and will have immediate implications for the management of this patient population.
Evaluation: This is Phase II study shows that the addition of the ICI Nivolumab increases the pathologic compete response rate (pathCR) and overall survival compared to chemotherapy alone. Neo-adjuvant immunotherapy and immunotherapy/chemotherapy combinations have been under investigation and this study adds to the growing body of literature that chemo + IO in this patient population is safe and more efficacious than chemotherapy alone.
Title: Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1
Link: 10.1016/j.jtho.2023.04.021
Rating: 6. Would change my management for patients with CNS disease.
Evaluation: Nice article. There certainly seems to be better CNS penetrance with IO when compared to platinum doublet. Interesting that comparator was to platinum doublet chemotherapy without pembrolizumab which is not current standard of care for metastatic NSCLC. Both OS and trend toward reduction in new CNS metastasis are thought provoking nonetheless. Would like to see Checkmate 9LA which utilizes only two cycles of CTLA-4 to cut down on long-term toxicities. If I had a fit patient with CNS disease I would certainly consider ipi-nivo up front.
Title: First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a multicentre, open-label, randomised, phase 3 trial
Link: https://pubmed.ncbi.nlm.nih.gov/37591293/
Rating: 5. 5 was warranted given it has the potential to be incorporated into treatment; however, given existence of other immunotherapies in the same space (ex: Pembro), it is hard to figure it will become more popular unless there is a head to head comparison showing superiority.
Evaluation: This is nice study that evaluates upfront single-agent cemiplimab in patients with PD-L1 ≥50% lung cancer that showed significant improvements in PFS and OS compared to standard chemotherapy doublets. It offers a nice addition for approved PD1 inhibitors in the front line setting of advanced NSCLC. Given immunotherapy +/- chemotherapy as part of upfront therapy for PD-L1 high patients has already been established, the control arm of chemotherapy alone does raise concern regarding true magnitude of PFS and OS of cemiplimab. In addition, it does not address whether front-line cemiplimab as a single agent has the same efficacy as front-line cemiplimab + chemotherapy would have. Studies evaluating efficacy of other immunotherapy agents, such as pembrolizumab, in this setting do address this question more forwardly. The benefit of cemiplimab may be more prudent then if there is limited access to other agents that have already been approved for this indication that have had better control arms in evaluating single agent benefits.
Breast Cancer
Title: Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer
Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2302344
Rating: 7. 7 was warranted because this definitely has the potential to influence the treatment of older patients or those with more comorbidities. Pending additional work, may not immediately recommend to younger cohort of patients.
Evaluation: The optimal balance of risk-reducing interventions and their harms is challenging in early-stage breast cancers, especially in those with lower-risk disease. This study helps enrich potential options for reduced intensity of therapies for these lower-risk women by forgoing radiation therapy after BCT as well as highlights the absolute necessity and role for hormone therapy in HR+ patients. The ipsilateral and contralateral recurrences were about 2% with the omission of radiation in a select group of women ≥55 years old. The follow-up was limited at 5 years limiting some of the survival and recurrence data. However, this may be an excellent addition for women ≥70 in whom SLNB can be omitted to further reduce intensity of therapies. For younger women, it may be more risk/benefit conversation, especially for those younger than 60-65, that may also be balanced with conversations of extended hormone therapy beyond 5 years.
Title: Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study
Link: 10.1016/S1470-2045(23)00268-1
Rating: 4. Disappointing study, but did appreciate the use of Ki67 decrease as surrogate for tumor response.
Evaluation: Interesting article testing a new SERD giredestrant vs. anastrazole in combination with palbociclib in the neoadjuvant space. They are utilizing Ki67 reduction as a surrogate for tumor response to endocrine therapy – a novel concept to me. Giredestrant seems to have a barely significant (p = 0.043) reduction in Ki67 compared to anastrozole. Tolerability is relatively equivalent. Although critically important that they included race in demographic data it is very unfortunate that only 3 total black patients were enrolled across the entire trial – a real missed opportunity. Also cost for giredestrant is probably a lot higher than anastrazole for a marginal bang for your buck.
Title: Neoadjuvant Talazoparib in Patients With Germline BRCA1/2 Mutation-Positive, Early-Stage Triple-Negative Breast Cancer: Results of a Phase II Study
Link: https://doi.org/10.1093/oncolo/oyad139
Rating: 3. Keynote 522 is a regimen that has relatively great results and although in the BRCA+ space, I still think would be first choice
Evaluation: Phase II article for neoadjuvant germline BRCA+ TNBC. Not head to head against KEYNOTE 522 so comparing to anthracycline/taxane-based chemotherapy regimens without immunotherapy. PCR rate of 45.8% is lower than KEYNOTE 522 – cross-trial comparisons aside would probably not incorporate into practice unless there were contraindications to IO. I always appreciate including patient-reported outcomes as an endpoint.
