Kartik Konduri, MD

 In the last few years, we have been able to improve outcomes for extensive-stage small cell lung cancer for patients by using new therapies, such as immunotherapy, which we have not been able to do over the last 15 to 20 years. This is certainly a promising outcome, and we need to build upon it. There are new medicines that are being combined with immunotherapy and other investigational drugs such as PARP inhibitors, bispecific antibodies, antibody drug conjugates, which are on clinical trials.

My advice to my colleagues practicing community-based oncology is to be aware that newer medicines are now available for standard first- and second-line therapies for extensive-stage small cell lung cancer. This is a very aggressive disease, and any improvements that we can provide to our patients are deeply appreciated.

Clinical trials using new therapies, such as PARP inhibitors, bispecific antibodies, as well as antibody drug conjugates are being evaluated. And the use of immuno-oncology in the limited-stage small cell lung cancer stage of disease is also being assessed. Therefore, if we can look forward [to] these trials and encourage participation of our patients, we hope to help improve outcomes for our patients in this very aggressive disease.

COVID-19 [coronavirus disease 2019] has certainly proposed challenges for helping take care of our patients in this day and age. However, many of our clinics and practices have learned how to deal with it and encouraged safety protocols that were put in place so that we have an ability to help take care of our patients’ safety and efficaciously. Telemedicine is something that we are using at this point of time to try to monitor our patients in between treatments so that we can assess for toxicities and side effects hopefully in the near future.

Case: A 68-Year-Old Woman with Extensive-Stage Small-Cell Lung Cancer

A 68-year-old woman presented with fatigue and a cough

PE: decreased breath sounds in the left lung, cervical lymph node enlargement

Lymph node biopsy showed small cell carcinoma

Chest/abdomen/pelvic CT showed a 7.4 cm mass above the diaphragm, a small contralateral lung nodule and evidence of invasion into the left side of the pericardium

PET scan showed activity in both lungs, above the diaphragm with small hypermetabolic activity in the surrounding area

Contrast‐enhanced MRI of the head was negative for brain metastases

Stage IV extensive-stage small-cell lung cancer; ECOG PS 0



Initiated carboplatin + etoposide + atezolizumab for 4 cycles; followed with atezolizumab as maintenance therapy

Repeat CT scan showed a suspicious hepatic mass

Initiated lurbinectedin 3.2 mg/m2 IV q21 Days

Videos

Kartik Konduri, MD, comments on the future of treating extensive-stage small cell lung cancer and provides advice for community oncologists treating patients with the disease.

The Future of Treating Small Cell Lung Cancer

 The Trigo et al trial that utilized lurbinectedin was a single-arm phase 2 study which incorporated 9 tumor subtypes. The trial encompassed 105 patients with small cell lung cancer, and this publication pertains to those patients. The trial was conducted between 2015 to 2019, and the median duration of follow-up was approximately 17 months.

In these 105 patients, the inclusion and exclusion criteria were to particularly involve patients who have progressed after at least frontline therapy. All patients had previously been exposed to platinum-based compounds. Patients who had CNS [central nervous system] metastases were excluded in this particular trial. The trial evaluated a primary endpoint for outcome was overall response rate. Other endpoints that were evaluated included duration of response, progression-free survival [PFS], as well as overall survival [OS]. Small post hoc analysis for immunotherapy-based patients and the outcomes was also evaluated.

This trial utilized lurbinectedin at 3.2 mg2 every 3 weekly basis given IV [intravenous]. It incorporated possibilities of dose interruptions and dose delays, and although primary prophylaxis with G-CSF [granulocyte colony-stimulating factor] was not allowed, secondary prophylaxis was allowed in this trial. Thirty percent of the patients in this trial had limited-stage small cell lung cancer on initial diagnosis. Whereas 70% had extensive-stage disease. Approximately 60% of these patients had previously had prophylactic cranial irradiation. Performance status of ECOG [Eastern Cooperative Oncology Group] 0, 1, or 2 were allowed, although only a small proportion of patients were ECOG 2.

A prespecified subgroup analysis of patients with chemotherapy-free intervals less than 90 days and greater than 90 days was incorporated in the study evaluation. After a median follow-up of 17 months, the response rates in this trial were 35%. In the population of patients who had a chemotherapy-free interval of less than 90 days, the response rates were about 22%, with a median PFS of 2.5 months and a median OS of roughly 5 months. For those patients who had a chemotherapy-free interval of greater than 90 days, the median PFS was 4.5 months, the median OS was 11.9 months, and the response rates were 45%.

There was an updated analysis for a small proportion of 20 patients who had a prolonged chemotherapy-free interval of more than 180 days, and, in those patients, the median OS was 16.2 months with a response rate of 60%. In a small proportion of patients who received immunotherapy, about 60% of them had a durable response. Regarding the adverse events in this trial, many patients had abnormalities in the labs, including elevations in creatinine and presence of higher transaminases and liver toxicities. These were generally grade 1 and grade 2. Five percent of patients had grade 3 and beyond neutropenia, and 5% of patients had febrile neutropenia in this trial.

In general, it was felt that the trial study medicine was well tolerated. Overall, it suggests that this medicine is an active compound in the particular space of second-line small cell lung cancer patients. However, the caveat for this trial includes the fact that it was a single-arm phase 2 study. Although it included 105 patients, these were incorporated from a basket trial and also it is important to note that the patients did not have brain metastases when they entered into this trial.

In the past, there have been combinations of lurbinectedin with doxorubicin in a phase 1 setting which has suggested its significant improvement in response and, based upon that, a confirmatory phase 3 trial called ATLANTIS was conducted. This trial used a lower dose of lurbinectedin than what was used in the basket trial.

The lurbinectedin medicine was combined with doxorubicin and was compared with CAV [cyclophosphamide, adriamycin and vincristine] or topotecan for its outcomes. The primary outcome for this trial was OS, and we recently learned in a press release that the outcome for OS was not met. However, secondary endpoints including perhaps PFS was supposedly significant. We do not know all the data from this trial and, therefore, we keenly await presentation in future meetings to learn more about its efficacy.

Kartik Konduri, MD, describes the phase 2 basket trial of lurbinectedin in the treatment of extensive-stage small cell lung cancer.

Lurbinectedin in the Treatment of Small Cell Lung Cancer

 Small cell lung cancer which is extensive-stage disease has been defined to have a certain terminology that allows us to tell the pace of the disease, and its possible sensitivity to next line of treatment. We use terminologies like refractory disease for patients who are in frontline treatment and have progressed. After progression, if the patient has a chemotherapy-free interval of less than 90 days, we consider them to have a resistant relapse. If they have a relapse more than 90 days after the initial chemotherapy, then we consider them to have a sensitive relapse. And those who have very late relapses of more than 180 days are considered to have a sensitive disease that might potentially be treatable with frontline therapy again. This is also known as a rechallenge where data in the past has suggested that such patients who relapse after 180 days might have a significant benefit in their outcomes when challenged back with a frontline regimen.

We consider utilization of second-line treatment in patients who have progression, but we tailor it to be considerations for frontline treatment to be rechallenged, especially in patients who have a relapse more than 180 days. Their data has suggested that these patients may have yet another significant response when a rechallenge occurs if they have a late relapse of their disease.

For patients who relapse earlier than 180 days the considerations include the use of second-line chemotherapy options, and those options include, amongst other things, topotecan, and now the new option of lurbinectedin.

My personal experience with lurbinectedin mirrors the data that came from the basket trial. The drug seems, in my experience, to be relatively well tolerated. In the small number of patients that I have treated, the long-term efficacy is still to be determined.

Kartik Konduri, MD, discusses treatment options for extensive-stage small cell lung cancer.

Treatment Options in Small Cell Lung Cancer

 Welcome to this case presentation of extensive-stage small cell lung cancer.

I’m Kartik Konduri, a thoracic medical oncologist at the Baylor Charles A. Sammons Cancer Center in Dallas, Texas.

This case begins with a patient who is a 68-year-old lady who presents with fatigue and cough with a past medical history of a hysterectomy at the age of 55, a social history of a 55-pack-year smoking history. And, on physical examination, the patient has decreased breath sounds in the left lung and cervical lymph node enlargement.

In the clinical workup of this patient, all labs are within normal limits. The lymph node biopsy shows small cell carcinoma. A chest, abdomen, and pelvic CT [computed tomography] scan shows a 7.4 cm mass above the diaphragm, and a small contralateral lung nodule is visualized with evidence of invasion into the left side of the pericardium. A PET [positron emission tomography] scan shows activity in both lungs above the diaphragm with small hypermetabolic activity in the surrounding area. A contrast enhanced MRI [magnetic resonance imaging] of the head was performed and is negative for brain metastases. The patient is staged as stage IV extensive-stage small cell lung cancer. The patient’s performance status is ECOG [Eastern Cooperative Oncology Group] 0.

Coming to treatment for this patient, the patient is initiated on carboplatin and etoposide, and atezolizumab for 4 cycles, followed by atezolizumab as maintenance therapy. A repeat CT scan shows a suspicious hepatic mass, and the patient then gets initiated on lurbinectedin at 3.2 mg/m2 IV [intravenous] every 21 days.

This case denotes a common presentation for small cell lung cancer. Many of our patients who are initially diagnosed are seen to have stage IV disease, and, unfortunately, this patient also has findings of disease in the contralateral lung as well as in the supraclavicular lymph node. The patient is treated with standard-of-care therapy with chemotherapy and immunotherapy treatments, and because of a progression, the patient is switched over to a second-line treatment.

Small cell lung cancer comprises about 15% of lung cancers in the United States. Of the 220,000 rough number of patients who are diagnosed with lung cancer, 15% to 20% of patients have small cell lung cancer. It is a disease most commonly seen in smokers and predominantly with patients who have a history of heavy smoking, although there is a small proportion of patients who have never smoked or very minimally smoked who also can present with this disease. Many times, patients with small cell lung cancer have tumors which have multiple genetic abnormalities. These may include 

In general, the prognosis for patients such as this one has been in the range of approximately 8 to 10 months, but with the advent of chemotherapy and immunotherapy recently, we have been able to improve outcomes with a medial overall survival [OS] of approximately 12.5 months. There have been developments of newer therapies that have come into our armamentarium for treatment for small cell lung cancer.

The treatment options for this patient at diagnosis include consideration for chemotherapy with immunotherapy, a clinical trial, or their consideration for straight up chemotherapy alone if there is a contraindication for the immunotherapy.

In the evaluation of our patients who have extensive-stage small cell lung cancer, we usually consider utilization of chemotherapy and immunotherapy as a standard first-line therapy treatment option for our patients. This is based upon a couple of large trials using chemotherapy with immunotherapy which have shown an improvement in OS for our patients. We consider factors such as performance status, brain metastases, as well as end organ function status in our approach to using treatment options for our patients.

Kartik Konduri, MD, evaluates the case of a 68-year-old woman with extensive-stage small cell lung cancer.

Kartik Konduri, MD | Authors

Articles

The Future of Treating Small Cell Lung Cancer

Lurbinectedin in the Treatment of Small Cell Lung Cancer

Treatment Options in Small Cell Lung Cancer

Evaluation of a Patient with Small Cell Lung Cancer