Monthly Article Review: November 2023
Dr. Matthew Mirsky, Dr. Matthew Hadfield, Dr. Jesse Drapekin, John Syme


Primum’s mission is to help every patient receive the best care, close to home. To deliver the best care, oncologists need to stay up-to-date with the latest advances in the field– a huge challenge when a new therapy is approved nearly every week while your attention is on the 20-30 patients who need you every day.

We know that inboxes are full of newsletters and alerts of recent advances. To help cut through the noise, Primum worked with 3 oncology fellows to find, rate, and summarize interesting, recently published articles. Each article has a rating on a scale of 1 to 10 describing the likelihood the work will be implemented in their practice. Check out the articles grouped by disease area and ranked by likelihood of changing practice below.

This Month's Articles

Lung Cancer

Title: Perioperative Nivolumab and Chemotherapy in Stage III Non–Small-Cell Lung Cancer


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


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


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


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.

Immune-related Adverse Events

Title: Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium


Rating: 10. This will immediately change the practice of oncology given no study of this size has ever been conducted to evaluate the incidence of IrAEs in patients with HIV. With the paucity of clinical trial data in this patient population this will serve as the only body of evidence to support using immunotherapies in patients with HIV.

Evaluation: This is a landmark paper in the utilization of ICIs for patients with solid tumors. Historically patients with HIV have been excluded from trials evaluating anti-PD1/PDL-1 therapies. This represents the largest study to ever evaluate the incidence of immune-related adverse events in patients with HIV and demonstrates no difference in the development of toxicities.


Title: Atezolizumab for Advanced Alveolar Soft Part Sarcoma


Rating: 8. Nice to have an option that is relatively easily tolerated for this histologic subtype.

Evaluation: Alveolar Soft Part Sarcoma (ASPS) is a very rare but very challenging disease to treat – even for a sarcoma. This is a phase II trial that was able to enroll 52 ASPS patients and shows a 2 year DOR with single-agent atezolizumab. They are currently evaluating the addition of bevacizumab a la HCC or CTLA-4. Good study, I would definitely treat any ASPS with atezo +/- bev


Title: Phase 3 Trial of Concizumab in Hemophilia with Inhibitors


Rating: 4. 4 was warranted for 3 main reasons: (1) It only carries approval in Canada for now (2) the rarity of acquired hemophilia patients that would require 3rd/4th line therapies (3) Difficult to know how to best sequence this with other treatments (emicizumab) that may have better data and provider experience with use 

Evaluation: Treating acquired hemophilia can present a real challenge for both management and prevention of bleeding with a majority of strategies reliant on immunosuppression and bypassing agents. The currently available monoclonal bypassing agent, emicizumab, targets the intrinsic pathway. The introduction of concizumab as an additional agent that targets the extrinsic pathway is potentially a great alternative or addition to the treatment repertoire. The study demonstrated a very significant overall improvement in bleeding prevention with prophylaxis that was unaffected by anti-conizumab antibodies. There were initial concerns regarding thrombosis as a side effect of the medication, but on further study with reduced dosing this risk seems to have been abated. Additionally, it may serve as a powerful alternative in patients that develop resistance to alternate therapies, such as emicizumab.


The Primum team would like to thank Drs. Matthew Mirsky, Matthew Hadfield, and Jesse Drapekin for their opinions and write-up. If you’d like to help identify interesting articles alongside our current set of fellows, please reach out to John ( Also, this is our first month of this program, so please share your ideas on how to improve this series.

We will be back next month with more articles.

Dr. Matthew Mirsky, Dr. Matthew Hadfield, Dr. Jesse Drapekin, John Syme