Jyoti Malhotra, MD, MPH

Precision Medicine Perspectives in Small Cell Lung Cancer

series, leaders in the management of extensive-stage small cell lung cancer (ES-SCLC) reflect on the current therapeutic landscape and examine ways in which physicians can optimize treatment approaches for their patients. As new chemotherapy-based treatment approaches have emerged for the management of ES-SCLC, it has become all the more important for physicians to consider the impact of chemotherapy-induced myelosuppression (CIM). One of the historic management strategies of CIM has been the use of dose delays or reductions, potentially affecting the overall efficacy of treatment. The approval of trilaciclib for the prophylactic management of CIM has the potential to address this critical area of unmet need. Ahead, Jyoti Malhotra, MD, MPH, considers the role of trilaciclib in her clinical practice and discusses how it’s benefitted her patients.

How has the approval of trilaciclib impacted your clinical practice?

 Trilaciclib was approved in 2021 for the treatment of patients with extensive-stage small-cell lung cancer who are receiving chemotherapy with either platinum-etoposide or topotecan. Through the approval of this drug, we now have an option to prevent chemotherapy-related myelosuppression in these patients, not just for preventing neutropenia but also anemia and thrombocytopenia because trilaciclib impacts and targets trilineage hematopoiesis, which is a big advantage. Before the approval of this drug, we had been using G-CSF [granulocyte colony-stimulating factor], but that targets mainly neutropenia and not anemia and thrombocytopenia. There have been 3 trials that have been done which led to the approval. All 3 trials showed a significant improvement in the duration of neutropenia, percentage of patients who are getting severe neutropenia, incidents of blood transfusions during treatment, and quality of life. With the approval, we now have an option for these patients to prevent myelosuppression.

What has been your experience with using trilaciclib in your patient since its approval?

 The schedule of trilaciclib recommends that the drug is given intravenously on the same day that patients are getting chemotherapy. Patients don't have to come to clinic for additional visits. They get their treatments with this drug on the same day as their preplanned trips for the other agents. The drug is relatively well-tolerated. The occasional adverse event we have noted is local site reaction. That's minimized to an extent when we are using a mediport, but otherwise, it's a good drug to use in terms of adverse events. In terms of efficacy, we haven't noted in any of the published literature and the completed trials that it impacts the efficacy of the chemotherapy in any way, which is great. Therefore, I have to say that the drug is relatively easy to use and incorporate in clinical practice.

How frequently are you using trilaciclib in your patients?

 In my patients with extensive-stage small cell lung cancer, I'm considering it for the treatment of all patients. I usually approach this on a case-by-case basis, depending on what the patient's presentation is and what the indications are. In patients who are at high risk for myelosuppression, such as elderly patients, such as patients who already have lower blood counts even before starting treatment because of tumor involvement in their bone marrow, I strongly consider this drug. We also consider this drug in patients who are refractory to G-CSF during cycle 1. Therefore, we are increasingly using this drug in clinical practice. I think every patient should be considered for this drug, but it should definitely be strongly considered in patients at higher risk for myelosuppression.

To what extent has using trilaciclib simplified your approach to addressing chemotherapy-induced myelosuppression?

 When we use this drug, we run into fewer problems with continuing treatment. Using this drug enables us to continue treating patients and complete their treatment plans. There are fewer treatment interruptions or treatment delays. The other significant impact is on quality of life. The trials have also shown that it does lead to a better quality of life in these patients, making it easier for us to administer the chemotherapy for these patients.

What are the most pronounced changes or benefits that you're seeing in patients who receive trilaciclib?

 The most significant benefit I would say is in terms of fewer treatment delays and interruptions and the ability to give full doses of chemotherapy to the patients, which is very crucial because small cell lung can cancer is an aggressive form of lung cancer, and we want to give patients as much of their planned treatment as possible at the optimum doses. This does enable that. Definitely, the quality-of-life improvement is also a significant improvement because that is key for the patients to continue their treatment.

Videos

In this companion article, Dr. Jyoti Malhotra discusses her clinical experience using trilaciclib for the management of chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer. 

EP. 6B: Clinical Experience With Trilaciclib in Patients With Extensive-Stage Small Cell Lung Cancer 



Trilaciclib was approved in 2021 for the treatment of patients with extensive-stage small-cell lung cancer who are receiving chemotherapy with either platinum-etoposide or topotecan. Through the approval of this drug, we now have an option to prevent chemotherapy-related myelosuppression in these patients, not just for preventing neutropenia but also anemia and thrombocytopenia because trilaciclib impacts and targets trilineage hematopoiesis, which is a big advantage.

The schedule of trilaciclib recommends that the drug is given intravenously on the same day that patients are getting chemotherapy. Patients don't have to come to clinic for additional visits. They get their treatments with this drug [on the] same day as their pre-planned trips for the other agents. The drug is relatively well-tolerated.

In patients who are at high risk for myelosuppression, such as elderly patients, such as patients who already have lower blood counts even before starting treatment because of tumor enrollment in their bone marrow, I strongly consider this drug. We also consider this drug in patients who are refractory to G-CSF (granulocyte colony-stimulating factor) during cycle 1.

The most significant benefit I would say is in terms of fewer treatment delays and interruptions and the ability to give full doses of chemotherapy to these patients, which is very crucial because small cell lung can cancer is an aggressive form of lung cancer, and we want to give patients as much of their plan treatment as possible at the optimum doses.

In the third video of the series, Dr. Jyoti Malhotra from the Rutgers Cancer Institute of New Jersey shares expert insights on the benefits of using trilaciclib in clinical practice including considerations for chemotherapy treatment efficacy and patient quality of life.

As of May 1, 2022, Dr. Malhotra is no longer with Rutgers Cancer Institute; she is now affiliated with City of Hope.

EP. 6A: Benefits of Using Trilaciclib in Patients With Extensive-Stage Small Cell Lung Cancer in Clinical Practice 

Jyoti Malhotra, MD, MPH, a medical oncologist at Rutgers Cancer Institute of New Jersey and assistant professor of medicine at Robert Wood Johnson Medical School, discusses the preliminary efficacy signals of the combination therapy plinabulin, nivolumab (Opdivo), and ipilimumab (Yervoy) in patients with relapsed/refractory small cell lung cancer (SCLC).

Malhotra says there were promising efficacy signals observed in the 16 patients enrolled on the phase 1 trial (NCT03575793). There were 10 patients with immunotherapy-resistant SCLC and 6 patients had immunotherapy-naïve SCLC. Those with immunotherapy-naïve disease had a response rate of approximately 50%. Patients with immunotherapy-resistant disease had a promising 43% response rate, which was very exciting according to Malhotra.

Of note, patients who responded also had significant tumor reduction ranging from 45% to 99% in the first 2 to 3 weeks of treatment. Some of the data are still immature at the completion of the phase 1 portion of this trial. Malhotra says she is looking forward to seeing the survival benefits and other preliminary analyses. The single-arm phase 2 part of this study in patients with relapsed/refractory SCLC who have received prior checkpoint inhibition is ongoing to evaluate the preliminary signals of clinical activity and reduced immune toxicity.

Jyoti Malhotra, MD, MPH, discusses the preliminary efficacy signals of the combination therapy plinabulin, nivolumab, and ipilimumab in patients with relapsed/refractory small cell lung cancer.

Jyoti Malhotra, MD, MPH | Authors

Articles

EP. 6B: Clinical Experience With Trilaciclib in Patients With Extensive-Stage Small Cell Lung Cancer

EP. 6A: Benefits of Using Trilaciclib in Patients With Extensive-Stage Small Cell Lung Cancer in Clinical Practice

Plinabulin/Nivolumab/Ipilimumab Combo Shows Preliminary Activity in SCLC