Last Month in Oncology with Dr. Bishal Gyawali: June 2017

29 Jun 2017
Last Month in Oncology with Dr. Bishal Gyawali: June 2017

Independent ecancer blogger Dr Bishal Gyawali rounds up the latest publications in oncology.

The biggest oncology meeting of the globe, the ASCO Annual meeting, has just ended providing plenty new information that is of interest to everyone involved with cancer and cancer care. Every year, the ASCO Annual Meeting provides us with some important practice-changing results but unfortunately, these information of importance sometimes get drowned in the noise of a large number of hyped studies. Last year, I did a blog on the hopes and hypes from ASCO 2016 which was very well received. This year, I have done a video interview with Will Davies (ecancer Reporter) where we discuss the major studies presented at ASCO and how they can change oncology practice. I do recommend you all to go through the video for a quick round up. This would be a compact, unbiased “Best of ASCO” available for free.

In this blog, I review the major articles published in journals from June 2017, some of which were presented at ASCO 2017.

  1. Overall survival benefit with assessment of Patient Reported Outcomes: This was one of the plenaries presented at ASCO and appropriately gathered huge attention. I have discussed this in detail in my video, and you can read it further in this research letter published in JAMA. However, this is not the only study to show overall survival benefit with patient reported outcomes. Last year, a similar study of internet based tool allowing patients to self-score and record their symptoms had shown a survival benefit of 7 months. I have discussed that study in detail in a previous blog. These studies together show that patients are their own best doctors, and engaging them in their care is not an emotional ideal, but an impactful intervention with real survival benefits.
  2. APHINITY-more is less? Pertuzumab was a revolutionary drug in the treatment of metastatic HER 2 positive breast cancer improving OS by more than a year. It has also shown efficacy in neoadjuvant setting. However, the results with addition of pertuzumab to trastuzumab in the adjuvant setting look disappointing with only a small benefit in disease free survival. There is no need for me to explain the caveats in detail as it has superbly been done in the excellent editorial accompanying this article. Also noteworthy, another trastuzumab biosimilar has shown equivalence in a phase 3 RCT increasing competition that hopefully lowers the price.
  3. Less is more in melanoma. Lymph node dissection in melanoma patients with positive sentinel nodes didn’t improve survival but increased lymphedema. The accompanying editorial is great again. It remains to be seen how early and widespread will the de-adoption of lymph node dissection happen because somehow abandoning a practice seems very difficult in medicine, despite having data to the contrary.
  4. ALEX confirms J-ALEX. Alectinib has significantly improved PFS versus crizotinib as first-line therapy for ALK lung cancer patients in the ALEX trial. This is a nicely done study reported in NEJM under the first-authorship of Dr. Solange Peters who should be duly congratulated also for getting selected as the ESMO President for 2020-2021. However, I am interested to see mature OS data because alectinib is a good drug to use in second line among patients who have developed resistance to crizotinib. Using alectinib upfront might take away crizotinib as an option because the efficacy of crizotinib post alectinib is not established. In ASCEND-5, ceritinib has shown better PFS after progression on crizotinib; but the place for ceritinib in the current treatment landscape is questionable because certainly alectinib would be used before ceritinib either in first line or after crizotinib. Ceritinib also has no head-head data against crizotinib, unlike alectinib.
  5. Complexity in treating hormone sensitive prostate cancer: The addition of abiraterone to androgen deprivation therapy plus prednisone for hormone naïve prostate cancer has significantly and impressively improved OS in two big trials presented at ASCO: STAMPEDE and LATITUDE. Another report from the STAMPEDE has previously shown that the addition of docetaxel upfront also improves OS. Thus, the question that remains is whether to use docetaxel or abiraterone upfront in addition to androgen deprivation therapy. I discuss this in detail in the ASCO round-up video.
  6. The paradox of screening:  Drs. Welch and Fisher have done a new analysis assessing overdiagnosis and overtreatment with income status across the U.S states. This analysis has shown that although more cancers are being diagnosed in the richer states, the mortality rates stay similar compared to the poorer states. That would imply that the richer states are simply suffering overdiagnosis. Another nicely titled article also appears together asking Are Small Breast Cancers Good because They Are Small or Small because They Are Good?
  7. Does the MONARCH have clothes? Abemaciclib has improved PFS in hormone positive breast cancer with a nice hazard ratio of 0.55. But so did bevacizumab, everolimus and palbociclib-all of which failed to subsequently improve OS. It’s early to tell but I won’t be surprised if this MONARCH also bites the dust.
  8. Whose value framework is more valuable? Measuring value is a difficult concept in cancer care. Putting a price on survival is all the more complex because of emotional and humanity issues attached. We have discussed this in detail here. 2 years ago ASCO and ESMO took a bold step and developed the value framework and the Magnitude of Clinical Benefit Scale respectively. Now, two studies asses their concordance: one published in Lancet Oncology and the other in JCO. However, there’s not much point in saying whether ASCO or ESMO delivered better framework; the most important thing is to provide better drugs at better value and this requires price negotiations or some bold steps to curtail prices/approval.
  9. Personalized dosing: In a remarkable analysis, Daniel Goldstein and colleagues have shown that the use of weight based dosing of pembrolizumab for lung cancer can save U.S 0.8 billion dollars annually. We need to explore more of such clever strategies to reduce unnecessary cancer costs.
  10. Pembrolizumab checkmates Nivolumab. Checkmate 026 was a milestone in the nivolumab versus pembrolizumab competition as Nivolumab failed to meet its primary endpoint in first line non-small cell lung cancer. The results are now published in NEJM, which was surprising to me as I seldom find NEJM publishing trials with negative results. Nivolumab failed to improve both PFS and OS versus chemotherapy in first-line. However, you might notice beautiful separation of curves in figure 2C and assume that nivolumab might be better in patients with high mutation burden, but that would be incorrect because this is an unplanned subgroup analysis in an attempt to salvage this expensive drug.

Bishal Gyawali, MD is a postgraduate trainee in medical oncology at the Graduate School of Medicine, Nagoya University, Japan, where he is also a PhD candidate under the Japanese government scholarship. He is also a medical consultant at Anticancer Fund, a not-for-profit organization based in Belgium as well as holds an affiliation at Institute of Cancer Policy, UK. His areas of clinical and research interests include evidence-based oncology practice, global oncology, cancer policy, cancer management in resource-limited settings, financial toxicities of cancer treatment, clinical trial methods and supportive treatment of cancer. He has no conflicts of interest to declare. Dr Gyawali tweets at @oncology_bg. Read his previous blog posts here.