September 2019 Edition Vol.11, Issue 8

Lung Cancer News, Regulatory Actions, and Insight — Summer 2019

Compiled by OBR Staff

There are so many studies, so many products and combinations of products in development, and so many different patient types, how does one keep on top of it all? This summer alone, defined as immediately post-ASCO through Labor Day, there were several key studies and events that clarified, or in some cases clouded, the treatment landscape for lung cancer patients.

We have assembled here the larger “reveals” in lung cancer over the summer, and to help put these reveals in perspective we’ve added commentary/analysis from OBR Editorial Board member Jack West, MD.  We hope that seeing the events and the interpretation together will help you understand and keep track of the evolving lung cancer landscape.

Update on the Phase III NEPTUNE Trial of Imfinzi Plus Tremelimumab in Stage IV Non-Small Cell Lung Cancer
(AstraZeneca) August 21, 2019 – AstraZeneca today announced final overall survival (OS) results from the Phase III NEPTUNE trial, a randomised, open-label, multi-centre, global trial of Imfinzi (durvalumab) in combination with tremelimumab, an anti-CTLA4 antibody, vs. standard-of-care (SoC) platinum-based chemotherapy in previously-untreated Stage IV (metastatic) non-small cell lung cancer (NSCLC) patients.

(Posted August 21, 2019) – “Disappointing but not surprising. Despite the recent press release about CheckMate 227 results showing nivo/ipi beating chemo alone in first line NSCLC, the combination doesn’t come close to deserving to displace the chemo/pembro combinations or pembro monotherapy that have handily beaten chemo already and are the current standards of care. And nivo/ipi has at least had some positive traction, while durva/treme has failed in every lung cancer setting in which it has been studied.

The durva/treme regimen deserves to be relegated to “asked and answered” status in lung cancer research. It has failed every way it can. In the process, it has only dampened enthusiasm for the concept of IO combinations and the potential benefit of TMB in clinical decision making, concepts that are on the cusp of being integrated at least into the margins of practice but are more questionable with the release of these findings.”

PharmaMar Will Submit NDA for Lurbinectedin Under Accelerated Approval in SCLC in the USA
(Yahoo! Finance) August 19, 2019 – New Drug Application (NDA) for lurbinectedin for second-line treatment of small cell lung cancer (SCLC) will be submitted under accelerated approval regulations pursuant to discussion with FDA. The filing, anticipated in the fourth quarter of 2019, will be based on data from the Phase II basket trial.

(Posted August 20, 2019) – “If FDA approved, lurbinectedin will emerge as a compelling alternative to topotecan, which remains one of the least favored standards of care in oncology. Many will still be holding out for randomized data with lurbinectedin, which should be provided in the ATLANTIS trial, which is looking at lurbinectedin with doxorubicin. If that trial is positive, I suspect that most people will actually favor using lurbinectedin as a single agent, given the additive myelotoxicity of these agents.”

FDA Approves Roche’s Rozlytrek™ (Entrectinib) For People with ROS1-positive, Metastatic Non-Small Cell Lung Cancer and NTRK Gene Fusion-Positive Solid Tumours
(Roche) Aug 16, 2019 – First FDA-approved treatment designed to target both ROS1 and NTRK that also shows response in cancer that has spread to the brain. Roche’s first FDA-approved tumour-agnostic medicine.

(Posted August 16, 2019) – “Another remarkably active drug for these small subsets of patients.”

AZ’ Tagrisso Improves Overall Survival in Lung Cancer
(PharmaTimes [UK]) August 9, 2019 – AstraZeneca has announced positive overall survival (OS) results from the Phase III FLAURA trial, evaluating Tagrisso (osimertinib) in previously-untreated patients with locally-advanced or metastatic non-small cell lung cancer (NSCLC).

(Posted August 9, 2019) – “An important and unsurprising result after seeing the immature but encouraging survival curves presented at ESMO 2017, this OS benefit crystallizes osimertinib as first line standard of care with superior efficacy, better tolerability, and the best CNS activity/control among EGFR TKIs. However, it will be worth paying attention to what proportion of patients received subsequent therapies, because if the majority of patients on this global trial never received treatment beyond their first line treatment assignment, FLAURA will confound variables of first line osimertinib and overall optimal treatment of EGFR mutation-positive patients over time.

In the US and many other health care systems, EGFR mutation-positive patients get several lines of therapy over many years, as they tend to have modest progression at a time of acquired resistance and should still be candidates for subsequent systemic therapies. If that isn’t happening for the majority of patients, it should call into question the health care system that is delivering such a low quality of care.”

Imfinzi Improves Overall Survival at Interim Analysis in the Phase III CASPIAN Trial in 1st-Line Extensive-Stage Small Cell Lung Cancer
(AstraZeneca) June 27, 2019 – AstraZeneca today announced positive overall survival (OS) results from the Phase III CASPIAN trial with Imfinzi in 1st-line extensive-stage small cell lung cancer (SCLC), a disease with significant unmet need and limited treatment options for patients.

(Posted June 27, 2019) – “An important trial result that is very similar in trial design to the IMpower133 trial of carbo/etoposide with either atezolizumab or placebo, CASPIAN also shows a significant survival benefit of platinum-based chemo (presumably cisplatin or carbo at physician discretion) with durvalumab. Because this is essentially the same finding as in IMpower133, the key issue will be whether the efficacy with durvalumab appears more impressive. There is clear room for improvement on the IMpower133 result, which showed a 2 month improvement in median overall survival (and hazard ratio of 0.7) that was sufficient to change the standard of care from chemo alone but didn’t blow away the lung cancer community. We await the presented/published results of the CASPIAN trial.

Also notable was the lack of mention of outcomes with durvalumab/tremelimumab combination with chemo, which presumably means it will again prove disappointing in a new lung cancer setting.”

FDA Approves Merck’s KEYTRUDA® (pembrolizumab) as Monotherapy for Patients with Metastatic Small Cell Lung Cancer (SCLC) with Disease Progression on or After Platinum-Based Chemotherapy and at Least One Other Prior Line of Therapy
(Merck) June 18, 2019 – Merck, known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy.

(Posted June 18, 2019) – “This approval should be obviated by integration of atezolizumab with chemotherapy as first line treatment for extensive stage small cell lung cancer based on the survival benefit of the IMpower133 trial. The data supporting this approval are relatively unimpressive. This is an approval the lung cancer community doesn’t really need, and it’s based on a clearly lower standard for approving this, nivo in the SCLC space, etc.

It will be a shame to have oncologists giving pembro (or nivo) after patients have progressed on chemo/atezo first line for extensive stage SCLC, but I fear that will happen far too often, with no data, a very weak rationale, and at a remarkably high cost for such a wasteful and unjustified (mis)use.”

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