(Lilly) Dec 11, 2019 - Eli Lilly and Company today announced the opening of the LIBRETTO-431 clinical trial [NCT04194944] for selpercatinib, also known as LOXO-292, for treatment-naïve RET fusion-positive non-small cell lung cancer (NSCLC) patients. Enrolled trial participants will be randomized to receive either selpercatinib or platinum-based (carboplatin or cisplatin) and pemetrexed therapy with or without pembrolizumab as initial treatment of their advanced or metastatic RET fusion-positive NSCLC.

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H. Jack West, MD (Posted: December 11, 2019)

Given the remarkable efficacy of selpercatinib, this is a trial that thoracic oncology experts debated the need for. It is arguable that it is worth doing a trial to test whether selpercatinib should be administered first line or is appropriate to defer until later, but selpercatinib has such impressive activity that thoracic oncologists would likely favor the pattern we have adopted for EGFR, ALK, ROS1, and other driver mutations for which the response rate exceeds 50% -- feeling that the "best drug first" approach, especially with a well tolerated agent/regimen, justifies pursuing the targeted therapy first line. Regardless, the trial will provide some information on a larger scale about the activity of selpercatinib, and the fact that the trial will allow crossover makes it ethically feasible. This will make it harder to interpret overall survival, but that is not the primary endpoint of the study. It will be helpful to see the difference in progression-free survival, likely quite profound, and also what proportion of patients cross over vs. lose that opportunity due to more significant progression.

(Xconomy San Francisco) Dec 4, 2019 - A Roche immunotherapy has won an additional FDA approval as a first-line treatment for non-small lung cancer, bolstering the product’s competitive stance versus one from Merck. The FDA approved atezolizumab (Tecentriq) for adults whose non-squamous non-small cell lung cancer (NSCLC) is metastatic, meaning it has spread, and does not have the EGFR or ALK genetic mutations.

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H. Jack West, MD (Posted: December 04, 2019)

Though I am the first author of the Lancet Oncology publication supporting this approval (IMpower130), I must admit that this indication should be anticipated to have limited utility. It is the same setting for which the combination of carbo/pemetrexed/pembrolizumab is approved and widely used since the April, 2018 presentation and NEJM publication of the KEYNOTE-189 trial (Gandhi et al, 2018). Of note, the IMpower150 trial of carbo/paclitaxel/bevacizumab as the control arm, with carbo/paclitaxel/bev/atezolizumab superior for OS also demonstrated a significant efficacy benefit even in patients with an EGFR mutation or ALK rearrangement (after progression on initial targeted therapy), though this wasn't seen in the EGFR/ALK+ subset on IMpower130 that did not include bevacizumab, suggesting that the inclusion of bevacizumab may be a key differentiator of benefit in this group -- though with the caveat that the subsets are not large enough to draw definitive conclusions. Overall, the carbo/nab-paclitaxel/atezolizumab regimen, pursued with the concept of obviating the need for steroid premedication that could abrogate the benefit of immunotherapy, is an option that is an appropriate consideration in first line treatment for advanced NSCLC but one that is unlikely to be favored over the far more readily adopted carbo/pemetrexed/pembrolizumab regimen.

(AstraZeneca) Nov 29, 2019 - AstraZeneca today announced that the US Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application (sBLA) and granted Priority Review for Imfinzi (durvalumab) for the treatment of patients with previously untreated extensive-stage small cell lung cancer (SCLC). SCLC is an aggressive, fast-growing form of lung cancer that recurs and progresses rapidly despite initial response to platinum-based chemotherapy.1 A Prescription Drug User Fee Act date is set for the first quarter of 2020.

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H. Jack West, MD (Posted: December 02, 2019)

This will provide a second option in the same setting for which we already have atezolizumab, first line extensive stage small cell lung cancer, and which produces the same results. This will not move the field forward.